Frontiers in Oncology

BackgroundWarthins tumor (WT) is the second most common parotid gland neoplasm with rising incidence. As some WT patients are not suitable for surgery, non-surgical treatment options are needed. This is the first study to evaluate the feasibility of ultrasound-guided bleomycin sclerotherapy (UGBS) for WT. Patients and methodsWT patients with concordant clinical, imaging, and cytology data were included. UGBS was proposed for patients who desired non-surgical intervention and fulfilled the inclusion criteria. Tumor volume and tumor-related symptoms were registered before UGBS and six months after. ResultsNine patients underwent UGBS between September 2021 and September 2022. In seven of the nine patients (78%), the tumor volume had diminished on average by 34% at six-month follow-up. Also, tumor-related pain, and cosmetic and functional discomfort decreased during the follow-up. One patient was later referred to partial parotidectomy. ConclusionUGBS could be an alternative non-surgical treatment for WT, especially for patients with risk factors for surgery.

BackgroundOver the past thirty years, numerous studies on primary central nervous system lymphoma (PCNSL) have been conducted, encompassing epidemiology, diagnosis, treatment, and mechanisms. However, no bibliometric analysis has been performed in this field. Therefore, we conducted a bibliometric analysis to elucidate the evolution and current status of PCNSL research and identify the most-cited articles across various disciplines. Material and MethodsLiterature published between January 1992 and June 2024 in the Web of Science Core Collection (WoSCC) was extracted and classified. Three platforms (R-bibliometrix, VOSviewer, and Citespace) were used for the bibliometric analysis. Negative binomial regression was employed to establish a model for the risk ratio of citation. ResultsA total of 1,798 publications were included in the analysis. The annual number of publications has shown a steady increase over time. The United States emerged as the leading country in terms of both the number of publications and total citations. Among individual researchers, Hoang-Xuan Khe from Sorbonne University was the most prolific in terms of publication count, while Lisa M. DeAngelis from Memorial Sloan Kettering Cancer Center received the highest number of citations. The study titled "Report of an International Workshop to Standardize Baseline Evaluation and Response Criteria for Primary CNS Lymphoma" was identified as the most cited work in this field. Keyword analysis indicated that immune therapy and non-invasive diagnosis are the primary focal points of current research. Among the top 100 most-cited articles, interventional studies demonstrated a higher citation ratio (RR = 1.357, 95% CI 1.044-1.764, P=0.023), whereas chemoradiotherapy studies exhibited a lower citation ratio (RR = 0.763, 95% CI 0.603-0.965, P=0.024). ConclusionResearch hotspots and trends in PCNSL were identified and explored using bibliometric and visual methods. The highly cited articles across multiple disciplines related to PCNSL may help generate high-quality research ideas, particularly in the fields of immunotherapy and non-invasive diagnosis.

PurposeTo spatially characterize the single-cell tumor microenvironment (TME) of salivary gland carcinomas (SGC) and identify prognostic biomarkers. Experimental DesignSGC, including salivary duct carcinomas (SDC), acinic cell, mucoepidermoid, and secretory carcinomas, were analyzed using a 13-marker imaging mass cytometry panel. Multichannel image data from 54 primary cases and nodal metastases were processed to generate single-cell datasets. Cell phenotypes (tumor cells, cancer-associated fibroblasts (CAFs), endothelia, immune cells) were classified using a validated CAF algorithm, followed by spatial analysis and clinicopathological correlation. ResultsAmong 509,364 cells, SDC exhibited the highest fractions of Collagen-and matrix-CAFs (mCAFs). Acinic cell carcinomas (ACC) showed enriched CD4+/CD8+ T cells and antigen-presenting CAFs (apCAFs), indicating strong immune infiltration. A spatially defined cellular neighborhood (CN8) of mCAFs and endothelia was elevated in SDC, with higher CAF infiltration in androgen receptor (AR)high versus ARlow SDC. Elevated mCAF frequency and CN8 were significantly associated with reduced recurrence-free probability (RFP) and distant control rates (DCR). Additionally, higher mCAF frequencies were an independent prognostic factor for decreased RFP and DCR in Cox regression analysis. ConclusionSDC are characterized by Collagen-/mCAF-rich microenvironments and mCAF-endothelial spatial interactions that are linked to metastasis. ACC display pronounced immune infiltration, suggesting its potential for immunotherapy. mCAFs in SDC emerge as prognostic biomarkers and therapeutic targets, highlighting the importance of targeting CAF-driven metastasis in future treatments. This study provides insights into the biology of SGC and identifies novel prognostic markers.

AbstractsO_ST_ABSBackgroundC_ST_ABSCancer patients are considered to be highly susceptible to viral infections, however, the comprehensive features of COVID-19 in these patients remained largely unknown. The present study aimed to assess the clinical characteristics and outcomes of COVID-19 in a large cohort of cancer patients. Design, Setting, and ParticipantsData of consecutive cancer patients admitted to 33 designated hospitals for COVID-19 in Hubei province, China from December 17, 2019 to March 18, 2020 were retrospectively collected. The follow-up cutoff date was April 02, 2020. The clinical course and survival status of the cancer patients with COVID-19 were measured, and the potential risk factors of severe events and death were assessed through univariable and multivariable analyses. ResultsA total of 283 laboratory confirmed COVID-19 patients (50% male; median age, 63.0 years [IQR, 55.0 to 70.0]) with more than 20 cancer types were included. The overall mortality rate was 18% (50/283), and the median hospitalization stay for the survivors was 26 days. Amongst all, 76 (27%) were former cancer patients with curative resections for over five years without recurrence. The current cancer patients exhibited worse outcomes versus former cancer patients (overall survival, HR=2.45, 95%CI 1.10 to 5.44, log-rank p=0.02; mortality rate, 21% vs 9%). Of the 207 current cancer patients, 95 (46%) have received recent anti-tumor treatment, and the highest mortality rate was observed in the patients receiving recent chemotherapy (33%), followed by surgery (26%), other anti-tumor treatments (19%), and no anti-tumor treatment (15%). In addition, a higher mortality rate was observed in patients with lymphohematopoietic malignancies (LHM) (53%, 9/17), and all seven LHM patients with recent chemotherapy died. Multivariable analysis indicated that LHM (p=0.001) was one of the independent factors associating with critical illness or death. ConclusionsThis is the first systematic study comprehensively depicting COVID-19 in a large cancer cohort. Patients with tumors, especially LHM, may have poorer prognosis of COVID-19. Additional cares are warranted and non-emergency anti-tumor treatment should be cautiously used for these patients under the pandemic.

ObjectiveProstate cancer (PCa) constitutes a considerable public health concern worldwide, primarily attributable to its elevated mortality rates. Changes in exosome are shown to significantly influence tumor development. This study aimed to investigate the prognostic value of exosome-related genes (ERGs) in PCa. MethodsPCa single-cell RNA sequencing (scRNA-seq) and transcriptome datasets were obtained from public databases, with ERGs extracted from existing literature. Candidate genes were identified by overlapping 6,004 PCa-related differentially expressed genes (DEGs) and 121 ERGs. Multiple algorithms screened prognostic genes to construct and validate a risk model. Function enrichment, immune infiltration, and drug sensitivity analyses were performed for high/low-risk groups, while scRNA-seq determined cell types via prognostic genes. ResultsA sum of 36 candidate genes was discovered at the intersection of 6,004 DEGs and 121 ERGs. NOC2L, RPS10, POSTN, and BIRC5 were selected as the prognostic genes. The survival status of PCa patients was effectively predicted by a risk model. The majority of pathways identified as significantly enriched between the 2 groups were related to cellular functions. Additionally, 7 differential immune cell types were identified between the 2 groups. RPS10 demonstrated the most significant negative correlation with immature dendritic cells. Chemotherapy drugs were more effective for PCa patients classified as low-risk group. Finally, epithelial cells, endothelial cells, and T cells were considered as key cells and played a critical role in PCa. ConclusionNOC2L, RPS10, POSTN, and BIRC5 were identified associated with exosome in PCa, providing a strong reference for exosome mechanisms in PCa.

The authors have withdrawn their manuscript because a major revision is in progress to incorporate additional data. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

(1) BackgroundGenomic Instability (GIN) plays a critical role in cancer progression and treatment response. Soft tissue sarcomas (STS), are characterized by high levels of chromosomal rearrangements and transcription-associated stress, both of which contribute to poor clinical outcomes. Current standard grading systems, such as FNCLCC, are limited in prognostic accuracy for STS, necessitating novel approaches for risk stratification and treatment guidance. To address this gap, we developed a holistic classifier, the MAGIC (Mixed transcription- and replication-associated GIN classifier), combining transcription- and replication-related GIN indices (iTRAC and iRACIN) to predict metastatic risk. (2) Patients and MethodsThis study utilized RNA sequencing (RNAseq) on 226 STS tumor samples to analyze fusions transcripts break points (BP) distribution and assess GIN. We computed MAGIC indices iTRAC and iRACIN, which are based on chromosomal instability linked to transcription and replication processes, respectively. iTRAC biomarker was evaluated against FNCLCC and CINSARC for metastatic risk stratification. Kaplan-Meier and iPART analyses were used to determine the prognostic relevance of iTRAC levels. (3) ResultsiTRAC significantly stratified patients with distinct metastatic outcomes, outperforming FNCLCC and CINSARC grading systems. STS patients with medium level of iTRAC showed the poorest metastasis-free survival. Patients classified as iTRAC high- and low-risk groups, achieved better prognosis. Furthermore, iTRAC stratified patients metastatic risk in treated and not treated patients, indicating poorer prognosis with chemotherapy in patients with low iTRAC and better for those with with medium iTRAC. (4) Conclusion(s)iTRAC demonstrates a superior prognostic utility in STS over current grading systems, effectively stratifying metastatic risk for patients who might benefit from alternative therapeutic strategies. iTRAC holds potential for personalizing chemotherapeutic approaches, paving the way for a new precision oncology approach in STS.

BackgroundProstate cancer is the most commonly diagnosed non-cutaneous malignancy in men and is the second-leading cause of cancer-related death. Castration-resistant pr ostate cancer (CRPC) persists despite low testosterone levels. MethodsIn this study, we investigated the combined effect of Celastrol and bicaluta mide on prostate cancer cells. We evaluated cytotoxicity, apoptosis, oxidative stress, ferro ptosis and the activation of the immune system in vivo and in vitro. ResultsOur findings revealed that the co-administration of Celastrol with bicalutamide enhanced cytotoxicity against prostate cancer cells, promoted cell apoptosis, induced oxi dative stress and ferroptosis. Importantly, it assisted bicalutamide in activating the immune system, triggering immunogenic cell death (ICD), and thereby enhancing immune thera py. This synergy resulted in a stronger anti-CRPC effect, improving the overall therapeutic efficacy. ConclusionOur study demonstrates the potential of the Celastrol and bicalutamide combination in treating castration-resistant prostate cancer. Further studies are warranted to explore the clinical application of this approach and its potential in improving patient outcomes. Funding informationThe author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by Beijing Municipal Natural Science F oundation (grant no. BFHHQS20240003).

Cell death mechanisms offer therapeutic strategies for bladder cancer, yet lack comprehensive bibliometric analysis. Map global research trends and hotspots in bladder cancer cell death mechanisms via bibliometrics. We analyzed 5,392 publications (1991-2024) from Web of Science using VOSviewer (co- authorship/keyword clustering), CiteSpace (citation bursts), and GraphPad Prism (statistics). Metrics included: (1) Temporal trends, (2) Country/institution contributions, (3) Journal impact, (4) Citation dynamics, (5) Collaboration networks, (6) Conceptual hotspots. China and the US led research output. Top institutions:University of Texas System (USA; 178 publications), UTMD Anderson Cancer Center (USA; 123), Nanjing Medical University (China; 122), Journal of Urology had the highest output (106 publications); Cancer Research (IF:12.5) the highest impact. Kim Wun-Jae was the most productive author (37 articles); Jemal A the most co-cited (446 citations). Keyword and citation analyses revealed emerging integration of cell death mechanisms with immunotherapy (IT) and photodynamic therapy (PDT) to overcome chemoresistance. This study delineates the evolution of bladder cancer cell death research and identifies IT/PDT as promising resistance-overcoming strategies grounded in targeted cell death pathways.

Natural killer/T cell lymphoma (NK/T L) is an aggressive malignancy associated with poor prognosis in relapsed patients. Although L-asparaginase based treatments are recommended as first-line treatment in relapsed patients, advances in immunotherapies such as checkpoint inhibitions have provided new therapeutic alternatives. However, as clinical outcomes for checkpoint inhibitors seemed to vary between NK/T L patients, combination therapies have been suggested to improve treatment efficacy. Here, we compared the effects of Daratumumab (anti-CD38)/anti-PD-1 combination therapy versus anti-PD-1 monotherapy on two relapsed NK/T L patients. Anti-PD-1 triggered an upregulation of CD38 on activated T cells, leading to depletion by Daratumumab. Concomittantly, EBV-specific antibody titer was also reduced alongside with depletion of CD38+ B cells and antibody-producing plasmablasts. Taken together, combining anti-CD38 and anti-PD-1 is likely to be antithetic.

BackgroundThis meta-analysis seeks to investigate the association between HPV and p16 status with overall survival in laryngeal and hypopharyngeal carcinoma. MethodsMedline, Scopus, EMBASE, and the Cochrane Library were used to identify studies for inclusion. Abstracts that discussed HPV/p16 status and prognosis in laryngeal or hypopharyngeal carcinoma were included. Next, full-text articles were screened and included based upon a checklist established a priori. Pooled hazard ratios for overall survival were generated using a random effects model. RevMan 5.3, Meta Essentials, and OpenMeta[Analyst] were used for statistical analysis. ResultsThirteen studies published between 2014 and 2019 with sample sizes ranging from 31 to 9,656 were selected for inclusion in this meta-analysis. The pooled data demonstrated that p16 status was not significantly associated with OS in either laryngeal or hypopharyngeal carcinoma with HRs of 1.03 (95% CI: 0.73-1.45; p = 0.88) and 1.02 (95% CI: 0.55-1.86; p = 0.96), respectively. The pooled data showed that HPV status was predictive of OS in laryngeal cancer with 0.63 (95% CI: 0.41-0.97; p = 0.03). ConclusionsOur results suggest that p16-positivity does not provide a survival benefit in LC and HPC. This is in contrast to studies in the oropharynx, where p16 status is a standard proxy for HPV infection and HPV infection is associated with improved prognosis.

PurposeInflammatory markers, such as Lymphocyte-to-Monocyte Ratio (LMR), Neutrophil-to-Lymphocyte Ratio (NLR), and Platelet-to-Lymphocyte Ratio (PLR), have been shown to hold significant prognostic value in the context of head and neck cancer (HNC). Recently, delta inflammatory markers, the difference between pre and post- treatment inflammatory marker ratios, have been suggested as potentially significant values in predicting cancer prognosis. Our objective was to evaluate the prognostic utility of delta LMR, NLR, and PLR in head and neck squamous cell carcinoma (HNSCC). MethodsRetrospective cohort study in a tertiary academic hospital setting. Patients diagnosed with HNSCC in the oral cavity, larynx, and oropharynx treated with curative intent treatment were included. The variables collected were age, sex, BMI, alcohol/tobacco exposure, performance scores, ACE-27, tumor characteristics, adjuvant treatment, ECOG score, and lab values. Overall Survival (OS) and Event-Free Survival (EFS) were chosen as endpoints. OS was defined as time from date of treatment to date of last follow-up or death from any cause, and EFS was defined as the start of treatment to any progression, recurrence, or death from any cause. Univariate and multivariate analyses were performed on the primary endpoints. ResultsA total of 89 patients were included from 2010 to 2017. In multivariate analysis, EFS was found to be significantly associated with an N stage of 3 (p=0.0005) and delta LMR > -1.48 (p=0.0241). No significant relationships were uncovered with OS in multivariate analysis. ConclusionA higher delta LMR value (>-1.48) was associated with poorer EFS, but was not associated with OS.

Most studies examining the causes of cancer-related deaths have primarily focused on specific cancer types, often neglecting the evolving spectrum of death causes among cancer patients in the 21st century. This study, utilizing data from the National Cancer Institutes Surveillance, Epidemiology, and End Results (SEER) Program, analyzed the causes of death in patients diagnosed with 36 types of cancer between 2000 and 2021. By categorizing these causes into deaths from index cancers, non-index cancers, and non-cancer causes, this study provides a comprehensive analysis of cause-of-death patterns and emerging trends, stratified by year of death, age at diagnosis, and survival duration. The findings reveal that while relative mortality rates from index cancers remain elevated for brain, pancreatic, and gallbladder cancers, significant declines were observed for lung, liver, nasopharyngeal, and esophageal cancers, as well as multiple myeloma cancers, reflecting advancements in cancer treatment. Besides, relative mortality rates from non-index cancers surpassed those from index cancers in oral cavity, oropharyngeal, vaginal, and small intestine cancers, indicating a potential benefit from enhanced surveillance and early detection of non-index cancers in these patient populations. Importantly, non-cancer-related causes of death, such as heart disease, chronic liver disease and cirrhosis, also emerged as prominent contributors to mortality among cancer patients. The results of this study offer critical and current data to inform public health policy, optimize healthcare resource allocation, and facilitate international collaboration in cancer research and control. Meanwhile, this study is of great reference value for developing countries to formulate medium- and long-term public health policies.

Circulating tumor DNA (ctDNA) has become an attractive biomarker in human oncology and may be informative in cancer-affected dogs. By performing ddPCR or PARR methods, we detected tumor-specific point mutations, copy number alterations and chromosomal rearrangements in the plasma of cancer-affected dogs. It allowed the detection of ctDNA in 2/8 (25%) oral malignant melanoma cases, 12/13 (92.3%) lymphoma cases and 21/23 (91.3%) histiocytic sarcoma (HS) cases. The value of ctDNA to diagnose HS was explored in 133 dogs including 49 with HS. In this cohort, screening recurrent PTPN11 mutations in plasma had a specificity of 98.8%, and a sensitivity between 42.8-77% according to HS clinical presentation, being higher in internal forms, especially with pulmonary location. Regarding lymphoma, the follow-up of four dogs showed that the minimal residual disease detection by targeting lymphoma-specific antigen receptor rearrangement in the plasma was concordant with the clinical evaluation. Moreover, ctDNA analysis appeared interesting to assess treatment response and to predict relapse. This study shows that ctDNA is detectable in the plasma of cancer-affected dogs and is a relevant biomarker for diagnosis and clinical follow-up. With a growing interest in integrating natural canine tumors to explore new therapies, this biomarker appears promising in comparative oncology research.

Cutaneous T-cell lymphoma (CTCL), particularly its tumor stage mycosis fungoides (MF) subtype, presents considerable therapeutic challenges since current treatment modalities show limited efficacy. This study addresses the unmet need for novel targeted therapies that inhibit the STAT3/5 pathway, which is hyperactive in CTCL. Utilizing a murine model with intradermally grafted malignant T-cell lymphoma cells, we compared the efficacy of the multi-kinase inhibitor IQDMA with the conventional, topical psoralen + UV-A (PUVA) phototherapeutic regimen. Our data show that IQDMA reduced tumor volume by 90.7% (p = 0.0001) and was significantly more effective than PUVA, which reduced the tumor volume by only 46.2% (p = 0.0074). Results of an immunobiological analysis reveal that IQDMA treatment decreased tumor cell infiltration by 29.8% (p = 0.03) and the percentage of Ki67+ cells by 25.3% (p = 0.03), indicating a reduced tumor cell proliferation rate. Moreover, remarkable 40.0% and 45.6% reductions were observed in the total STAT5 (p = 0.047) and STAT3 (p = 0.01) levels of the infiltrating tumor cells upon IQDMA treatment. STAT5 levels are directly correlated with CD3+ tumor cell infiltration, confirming the role of the STAT3/5 pathway in the disease pathogenesis. Intriguingly, while phospho-STAT5 and total STAT5 levels directly correlated in the vehicle-treated group, a negative correlation was observed in the IQDMA-treated group, indicating IQDMA action in blocking STAT5 hyperactivation. IQDMA targets PAK kinase, a nuclear transporter for phospho-STAT5; in turn, we observed a compartmental shift of phospho-STAT5 from the nucleus to the cytoplasm. These key findings establish the properties of IQDMA as a potent targeted therapy for CTCL and offer compelling evidence for its clinical evaluation.

BackgroundProstate cancer remains one of the most prevalent malignancies among men globally, with its incidence showing an upward trend worldwide. Mitochondria, as central regulators of cellular energy metabolism, play crucial roles in prostate cancer initiation, progression, and drug resistance mechanisms. While mitochondria-targeted therapeutic strategies have emerged as a significant focus in cancer research in recent years, comprehensive bibliometric analyses mapping the evolving landscape of this field remain scarce. This study systematically investigates research trends in mitochondrial-prostate cancer interactions through bibliometric methods, identifying LONP1 as an emerging research focus in mitochondria-related prostate cancer therapy. Building on these findings, we employed artificial intelligence to virtually design a LONP1-specific antibody, proposing novel therapeutic targeting strategies for this field. MethodsUtilizing the Web of Science Core Collection database (2015-2023), we conducted visualization analyses through CiteSpace and VOSviewer to map network relationships among countries, institutions, journals, authors, and keywords. Building on this foundation, a humanized antibody targeting LONP1 was computationally designed and screened through the GeoBiologics platform. ResultsAnalysis of 452 included publications revealed the United States and China as leading contributors in this research domain. The field has progressively transitioned from fundamental mechanistic investigations to clinical applications, particularly focusing on drug resistance mechanisms, and combination therapy. LONP1 was identified as a critical mitochondrial regulator strongly associated with prostate cancer progression. Our AI-designed antibody (Antibody_82) demonstrated superior binding affinity and stability through effective targeting of LONP1s ATP-binding site. ConclusionThis bibliometric study delineates evolving research trends in mitochondrial involvement in prostate cancer. The developed LONP1-targeting antibody shows promising therapeutic potential for castration-resistant prostate cancer (CRPC) patients, potentially offering more effective treatment alternatives.

BackgroundGastric cancer (GC) remains a leading cause of global cancer mortality, with a high prevalence of distant metastasis at diagnosis in Vietnam. Systemic inflammatory markers are emerging as potential tools for risk assessment, yet their independent predictive value in the Vietnamese population requires further clarification. ObjectiveTo evaluate the predictive value of the Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) as cost-effective biomarkers for distant metastasis in Vietnamese GC patients. DesignA single-center, retrospective cohort study of 114 GC patients treated at the Oncology Hospital of Ho Chi Minh City between January and June 2023. MethodsPatients were categorized into metastatic (Stage IV) and non-metastatic groups per AJCC 8th edition criteria. Pretreatment NLR and PLR were calculated from peripheral blood counts. The optimal cutoffs were determined using receiver operating characteristic (ROC) curve analysis. DeLongs test was employed to compare the diagnostic efficacy of the clinical model versus the combined clinical-hematological model. Univariate and multivariate binary logistic regression analyses were performed to identify independent predictors of distant metastasis. ResultsMetastasis was present in 44.7% of cases. Optimal cutoffs of 2.0 for NLR and 181.5 for PLR were identified. Both markers were significantly higher in the metastatic group (p<0.01) and positively correlated with disease progression. A combined model integrating clinical factors with NLR and PLR demonstrated superior diagnostic accuracy compared to clinical factors alone (AUC: 0.766 vs 0.619, p=0.0036). In multivariable analysis, multiple tumor location and high PLR remained independent prognostic factors for distant metastasis. ConclusionElevated NLR and PLR are significantly associated with distant metastasis in GC. Integrating these accessible, minimally invasive markers with clinical data enhances predictive accuracy, providing a practical tool for risk stratification in resource-limited settings. Plain Language SummaryO_ST_ABSThe ChallengeC_ST_ABSGastric cancer (stomach cancer) is a leading cause of cancer-related deaths worldwide. In Vietnam, many patients are diagnosed only after the cancer has already spread to distant parts of the body (metastasis). When cancer spreads, it becomes much harder to treat. Doctors need affordable and reliable ways to predict which patients are at a higher risk of metastasis to improve how they manage the disease. The StudyResearchers studied 114 gastric cancer patients at the Ho Chi Minh City Oncology Hospital. They looked at two specific markers found in routine, inexpensive blood tests: the Neutrophil-to-Lymphocyte Ratio (NLR) and the Platelet-to-Lymphocyte Ratio (PLR). These markers measure the balance of different white blood cells and platelets, which partially reflect the bodys "inflammation" levels in response to a tumor. The FindingsThe study found that patients with advanced, metastatic cancer had significantly higher NLR and PLR levels compared to those in earlier stages. By combining these blood markers with other clinical information--such as the patients and tumors data --the researchers created a predictive model. This combined model was much more accurate at identifying patients with distant metastasis than using clinical information alone. The ImpactBecause these blood tests are simple, low-cost, and already widely available in hospitals, they offer a practical way for doctors to monitor cancer progression. Using the NLR and PLR ratios can help healthcare providers in Vietnam and elsewhere better identify high-risk patients and personalize their treatment plans more effectively.

Colorectal cancer liver metastasis (CRCLM) is one of the deadliest cancers. CRCLM tumours have two distinct histopathological growth patterns (HGPs) including desmoplastic HGP (DHGP) and replacement HGP (RHGP). The DHGP tumours are angiogenic, while their RHGP counterparts are vessel co-opting. The patients with DHGP tumours have a better response to anti-angiogenic agents and chemotherapy, as well as the prognosis. To determine the influence of vitamin D supplementation in CRCLM, we analyzed the HGPs and the 5-year OS of CRCLM patients (n=106). Interestingly, we found an inverse correlation between vitamin D supplementation and the presence of RHGP tumours in CRCLM patients. Additionally, the 5-year OS of the patients that administered vitamin D was significantly higher. The cancer cells in RHGP lesions are characterized by direct contact with the hepatocytes, and this phenomenon enhances the motility of the cancer cells and facilitates their infiltration through liver parenchyma to co-opt the pre-existing vessels. Significantly, our in vitro data demonstrated the downregulation of motility markers in the co-cultured cancer cells with hepatocytes upon exposure to vitamin D. Altogether, this study highlights the role of vitamin D in CRCLM and provides a rationale to investigate the contribution of vitamin D supplementation to the prognosis of CRCLM patients.

PurposeCellular dynamics between phenotypically heterogeneous subpopulations of cancer cells within individual tumor is shown to be responsible for drug tolerance and overall poor prognosis; however, evidences were largely missing in oral cancer. Therefore, this study was undertaken to describe the dynamic phenotypic states among oral cancer cells, its influence on transcriptomic heterogeneity as well as its clinical significance. Experimental DesignWe multiplexed phenotypic markers of putative oral-stem-like cancer cells (SLCCs) and characterized diversity among CD44-positive oral cancer cell subpopulations with respect to distinct expression of CD24 and aldehyde dehydrogenase (ALDH)-activity in multiple cell lines. Population trajectories were characterized by Markov model and cell states were defined based on the population specific RNA sequencing (RNAseq). ssGSEA based gene expression signatures were explore for prognostic significance. ResultsOral cancer cells followed two distinct patterns of spontaneous repopulation dynamics with stochastic inter-conversions on ALDH-axis, however a strict non-interconvertible transition on CD24-axis. Interestingly, plastic ALDH-axis was harnessed to enrich ALDHHigh subpopulations in response to Cisplatin treatment, to adapt a drug tolerant state. Phenotype-specific RNAseq results suggested the organization of subpopulations into hierarchical structure with possible maintenance of intermediate states of stemness within the differentiating oral cancer cells. Further, survival analysis with each subpopulation-specific gene signature strongly suggested that the cell-state dynamics may act as possible mechanism to drive ITH, resulting in poor prognosis in patient. ConclusionsOur results emphasized the prognostic power of the population dynamics in oral cancer. Importantly, we have described the phenotypic-composition of heterogeneous subpopulations critical for global tumor behaviour in oral cancer; which is a prerequisite knowledge important for precision treatment, however largely lacking for most solid tumors. Graphical AbstractWe have characterized diversity among CD44-positive oral cancer cells lines with respect to distinct expression of CD24 and ALDH-activity. Subpopulations showed stochastic inter-conversions on ALDH-axis but a strict non-interconvertible transition of CD24Low to CD24High phenotype, even in response to chemotherapy-induced stress. RNAseq study suggested the organization of subpopulations into hierarchical structure with possible maintenance of intermediate alternate states of stemness within the differentiating oral cancer cells. The described population dynamics demonstrtaed influence tumor behaviour possibly by increasing intratumoral heterogeneity in aggressive oral tumors. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/457509v3_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@1dc6a7org.highwire.dtl.DTLVardef@dd0948org.highwire.dtl.DTLVardef@18c9603org.highwire.dtl.DTLVardef@cca8fb_HPS_FORMAT_FIGEXP M_FIG C_FIG Translational relevanceIntratumoral heterogeneity (ITH) has been the clinically important factor, impacting aggressive cancer behaviour, drug tolerance and overall poor prognosis. Recent high-throughput studies have provided better cellular and molecular resolution of ITH; however, the prerequisite knowledge which defines the composition of subpopulations critical for global tumor behaviour is majorly lacking for most of the solid tumors. By combining phenotypic markers, we have defined four subpopulations of oral cancer cells. These subpopulations showed stochastic inter-conversions as well as a strict non-interconvertible transition among them to acheive heterogeneity. Importantly, transcriptional states of each subpopulations indicated a clinically relevant signatures for patient prognosis. Also, we observed interconversions of these subpopulations in response to Cisplatin to accumulate drug-tolerant cell state, as rapid and reversible strategy to respond to chemotherapy induced stress. Thus, the characteristics of described phenotypic subgroups may be translated to the clinic for estimating the extent of intratumoral heterogeneity in oral cancer patients.

BackgroundThe standard initial treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (nCRT). In order to select patients who would benefit the most from nCRT, there is a strong need for predictive biomarkers. The aim of this study was to evaluate the role of clinical, pathological, radiological, inflammation-related genetic, and hematological parameters in the prediction of response after nCRT. MethodsIn silico analysis of published transcriptomics datasets was conducted to identify the best candidate genes, whose expression will be measured using quantitative Real Time PCR (qRT-PCR) in pretreatment formaline-fixed paraffin-embedded (FFPE) samples. In this study, 75 patients with LARC, between June 2020 and January 2022, were prospectively included. Patients were assessed for tumor response in the 8th week after nCRT completion with pelvic MRI scan and rigid proctoscopy. For patients with a clinical complete response (cCR) and initially distant located tumor no immediate surgery was suggested ("watch and wait" approach). The response after surgery was assessed using histopathological tumor regression grading (TRG) categories from postoperative specimens by Mandard. Responders (R) were defined as patients with cCR without operative treatment, and those with TRG 1 and TRG 2 postoperative categories. Non-responders (NR) were patients classified as TRG 3-5. ResultsResponders group comprised 35 patients (46.6%) and NR group included 53.4% of patients. Analysis of published transcriptomics data identified genes that could predict response to treatment and their significance was assessed in our cohort by qRT-PCR. When comparison was made in the subgroup of patients who were operated (TRG1 vs. TRG4), the expression of IDO1 was significantly deregulated (p<0.05). Among hematological parameters between R and NR a significant difference in the response was detected for neutrophil-to-monocyte ratio (NMR), initial basophil, eosinophil and monocyte counts (p<0.01). According to MRI findings, non-responders were more often presented with extramural vascular invasion (p<0.05). ConclusionBased on logistic regression model, factors associated with favorable response to nCRT were found to be tumor morphology as well as hematological parameters which can be easily and routinely derived from initial laboratory results (NMR, eosinophil, basophil and monocyte counts) in a minimally invasive manner. Using various metrics, an aggregated score of the initial eosinophil, basophil, and monocyte counts demonstrated the best predictive performance.