BMC Cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer and the majority of patients present with metastatic disease. Metastatic spread requires a reorganisation of the actin cytoskeleton, a process that is dependent on the Rho family GTPases and their interaction with subsequent downstream effectors. The p21 activated kinases (also known as the PAKs) are effectors of Rho GTPases Cdc42 and Rac and play key roles in cell migration and survival. PAK4 is overexpressed in PDAC and can reciprocally activate the PI3K pathway. Hepatocyte growth factor (HGF), via c-Met, is an established activator of PAK4 and the PI3K pathway and may promote PDAC invasion. Next generation sequencing (NGS) was performed on 31 PDAC tissue using a pre-determined targeted panel to attempt to identify novel mutations in the PAK: PI3K pathway. Targeted NGS identified several recurrent mutations including 5 PAK4 mutations in PDAC tissue.

BackgroundVarious treatments exist for non-melanoma skin cancer (NMSC), but the mainstay is surgical removal. Superficial radiotherapy (SRT) is one non-surgical technique that has been used for over a century but fell out of favor due to the advent of Mohs micrographic surgery (MMS). A new technology that combines a 22 megahertz (MHz) dermal ultrasound with SRT (US-SRT) enables tumor visualization before, during, and after treatment, and demonstrates increased cure rates and reduced recurrences. MethodsWe conducted a meta-analysis comparing the local control (LC) of four studies using traditional non-image-guided forms of radiotherapy for NMSC treatment to two seminal studies utilizing high-resolution dermal ultrasound-guided SRT (HRUS-SRT). The four traditional radiotherapy studies were obtained from a comprehensive literature search used in an article published by the American Society of Radiation Oncology (ASTRO) on curative radiation treatment of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and squamous cell carcinoma in-situ (SCCIS) lesions. The meta-analysis employed a logit as the effect size indicator with Q-statistic to test the null hypothesis. ResultsLC rates for the 2 US-SRT studies were statistically superior to the 4 traditional therapies individually and collectively. When stratified by histology, statistically superior outcomes for US-SRT were observed in all subtypes with p-values ranging from p < 0.0001 to p = 0.0438. These results validated an earlier analysis using a logistic regression statistical method showing the same results. ConclusionUS-SRT is statistically superior to non-image-guided radiotherapies for NMSC treatment. This modality may represent the future standard of non-surgical treatment for early-stage NMSC.

Background: KRAS mutation status is an important biomarker in rectal cancer, with implications for prognosis and treatment response. MRI-based radiomics has emerged as a non-invasive approach for predicting tumor genotypes. However, the diagnostic performance of MRI radiomics for predicting KRAS mutation status remains unclear. This study aimed to evaluate the diagnostic accuracy of MRI radiomics for predicting KRAS mutations in rectal cancer. Methods: A systematic search of PubMed, Cochrane Library, Scopus, and Web of Science was performed through July 2025. Diagnostic test accuracy studies evaluating MRI-based radiomics or artificial intelligence models for predicting KRAS mutation status in adult patients with rectal cancer were included, using molecular testing as the reference standard. Risk of bias was assessed using the QUADAS-2 tool. Pooled sensitivity and specificity were estimated using a bivariate random-effects model. Results: Seven studies involving 1,224 patients were included. The pooled sensitivity was 0.736 (95% CI: 0.697-0.772) and the pooled specificity was 0.645 (95% CI: 0.586-0.701). The false positive rate was 0.355 (95% CI: 0.299-0.414). The area under the hierarchical summary receiver operating characteristic curve was 0.754, with a normalized partial AUC of 0.666. Between-study heterogeneity ranged from low to moderate depending on the estimation method (I2 = 8.4%-53.3%). Conclusion: MRI radiomics demonstrates moderate diagnostic accuracy for predicting KRAS mutation status in rectal cancer and may serve as a promising non-invasive biomarker for preoperative molecular stratification. Further large-scale studies with external validation are required to confirm its clinical utility.

BackgroundSLIT2 has been shown to serve as a tumor suppressor in breast, lung, colon, and liver cancers. Additionally, expression of SLIT2 has been shown to be epigenetically regulated in prostate cancer. Therefore, we sought to determine transcriptional regulation of SLIT2 in pancreatic ductal adenocarcinoma. MethodsRNA expression of SLIT2, SLIT3, and ROBO1 was examined in a panel of pancreatic ductal adenocarcinoma cell lines while protein expression of ROBO1 and SLIT2 was examined in tumor tissue. Methylation of the SLIT2 promoter was determined using Sequenom while histone modifications were queried by chromatin immunoprecipitation. Reexpression of SLIT2 was tested by treatment with 5-aza-2deoxycytidine and Trichostatin A. ResultsPancreatic cancer cell lines fall into three distinct groups based on SLIT2 and ROBO1 expression. The SLIT2 promoter is methylated in pancreatic ductal adenocarcinoma and SLIT2 expression is dependent on the level of methylation at specific CpG sites. Treatment with 5-aza-2deoxycytidine (but not Trichostatin A) led to SLIT2 reexpression. The SLIT2 promoter is bivalent in pancreatic ductal adenocarcinoma and histone marks around the transcriptional start site are responsible for transcription. ConclusionsLoss of SLIT2 expression modulated by epigenetic silencing may play a role in pancreatic ductal adenocarcinoma progression.

IntroductionClassification of ovarian metastases (OM) in colorectal cancer (CRC) as peritoneal metastasis (PM) remains controversial. OM demonstrate resistance to systemic therapy, suggesting distinct molecular tumorigenesis. Gene expression profiling and transcriptomic analysis were performed to distinguish OM, PM, and primary CRC (pCRC) and identify potential therapeutic targets. MethodsRNA sequencing data were obtained from the Total Cancer Care database. After filtering out low-expressed genes, raw counts of retained genes were normalized in trimmed mean of M-values and then log2-transformed. Genes with a |Log2FC|>0.58 and adjusted p-value <0.05 were considered dysregulated. In silico motif enrichment analysis of estrogen receptor 1 (ESR1) on growth regulating estrogen receptor binding 1 (GREB1) was conducted. ResultsThere were 115 patients with tissue from OM (n=6), PM (n=4), and pCRC (n=105). Among upregulated genes, LAMC3, SCUBE1, and GREB1 had the highest differential expression in OM compared to PM, and PEG3, C7, and GREB1 had the highest differential expression in OM compared to pCRC (all p<0.001). GREB1 was upregulated in OM compared to PM and pCRC. There are two estrogen response element (ERE) sites within the promoter region of GREB1. ESR1 transcription factor was shown to bind to these ERE (p<0.001). ConclusionsTranscriptomic analysis demonstrated clear molecular distinction between OM, PM and pCRC. We identified upregulation of GREB1 in OM compared to PM and pCRC. GREB1 contains both ERE and ESR1 in the upstream promoter regions implying potential upstream transcription regulation mediated by ESR1. GREB1 may represent a novel, hormonal target in treatment of OM in CRC.

In high grade serous ovarian cancers (HG-SOC), BRCA1/2 mutations have been reported as the most predominant mutations by various studies. However, the non-mutational mechanisms of BRCA pathway inactivation in HG-SOC are unclear. We aimed to evaluate BRCA1 inactivation by estimating its expression along with its repressor in primary and neoadjuvant chemotherapy (NACT) treated HG-SOC tumors with known therapeutic response. The expression pattern of BRCA1 protein was evaluated by immunohistochemistry (IHC) in 119 cases of HG-SOC from a hospital cohort consisting of primary (N= 69) and NACT treated (N=50) tumors. Histological patterns (SET), stromal infiltration by lymphocytes (sTILs) and chemotherapy response score (CRS) were estimated by microscopic examination. Gene expression levels of BRCA1, and its repressor ID4 was estimated by qPCR. Association of BRCA1 protein and mRNA with clinicopathological features was studied. Relevance of the BRCA1/ID4 ratio was evaluated in tumors with different CRS. BRCA1 protein expression was observed in 12% of primary and 19% of NACT treated HG-SOC tumors. Moderate concordance was observed between BRCA1 protein and mRNA expression (AUC-0.677). High BRCA1 mRNA expression was significantly associated with more frequent SET pattern (p=0.024), higher sTILs density (p=0.042), increased mitosis (p=0.028). BRCA1 negative tumors showed higher expression of ID4 though not statistically significant. Higher BRCA1/ID4 ratio was associated with high sTILs density in primary (p=0.042) and NACT treated tumors (p=0.040). Our findings show the utility of BRCA1/ID4 ratio to predict neoadjuvant therapy response, which needs further evaluation in larger cohort with long term outcomes.

Colorectal cancer (CRC) and breast cancer (BC) are deadly diseases that rank as the second and fourth leading causes of cancer-related deaths, respectively. We have previously shown that miR-6883 targets CDK4/6 and that palbociclib-mediated CDK4/6 inhibition destabilizes HIF1. We hypothesize that miR-6883 downregulates HIF1 in CRC and BC cells. miR-6883 was transfected under normoxia or hypoxia and western blot analysis revealed that miR-6883 downregulates CDK4/6 and HIF1 in CRC and BC cells, pointing to miR-6883 as a promising therapeutic to target hypoxic cancers or HIF1-deregulated tumor cells. Future studies will further investigate miR-6883 as a cancer biomarker, effects on HIF-related proteins and therapeutic uses in vivo. O_FIG O_LINKSMALLFIG WIDTH=164 HEIGHT=200 SRC="FIGDIR/small/556385v1_fig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@e0acadorg.highwire.dtl.DTLVardef@68b428org.highwire.dtl.DTLVardef@bc4dforg.highwire.dtl.DTLVardef@aa13ad_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO miR-6883 downregulates CDK4/6 and HIF1 in colorectal and breast cancer cells A) Colorectal cancer cells were treated with doses of palbociclib ranging from 0-20 {micro}M. Cell viability was measured by imaging the bioluminescent signal after addition of CellTiter-Glo reagent. B) Percent viability of colorectal cancer cells treated with palbociclib was calculated and nonlinear regression analysis was completed using GraphPad Prism software. C-H) CRC cells were transfected with miR-6883 under normoxia or hypoxia (<0.5% O2) and protein levels of CDK4/6, HIF1, Glut1, and Ran were measured by Western blot. C_FIG

BackgroundHigh risk (HR) basal cell carcinoma (BCC) subtypes have been associated with high recurrence rates that is felt to be better managed surgically. Specifically, Mohs Micrographic Surgery (MMS) is considered most effective for aggressive HR BCCs and superior to traditional nonsurgical techniques, including radiation. Recently, superficial radiation therapy with high resolution ultrasound image guidance called Image Guided Superficial Radiation Therapy (IGSRT) displayed high local control (LC) rates and is an emerging non-surgical alternative to MMS for non-melanoma skin cancer (NMSC). ObjectivesWe present the largest experience in the USA on treatment of BCCs using IGSRT and specifically evaluate if there are differences in LC between HR BCC versus non-HR subtypes using this technology. MethodsA retrospective analysis was conducted on 7,994 BCC lesions treated with IGSRT in the continental United States. We compared the results of BCCs treated with IGSRT separated by HR vs non HR groups including 339 HR BCC lesions and 7655 non HR BCC lesions. High risk was defined as infiltrative, micronodular, morpheaform, and sclerosing subtypes. Non-HR BCC included superficial, nodular, and not otherwise specified (NOS) subtypes. Local control (LC) rates at two and five years were calculated with actuarial life-table and Kaplan-Meier methods and statistically compared using log rank tests. ResultsIGSRT treatment of the HR BCC group showed no recurrences with two and five-year actuarial and KM LC rates all at 100%. In comparison, the non-HR BCC cohort achieved similar two and five-year actuarial LC rates of 99.71% and 99.24% (KM LC at 99.5% and 99.23%), respectively. No statistical differences in LC rates between the two cohorts (p=0.278 each) resulted. Patients tolerated treatment well with little or rare high grade RTOG toxicity reported in both cohorts. ConclusionHR BCC may be treated just as effectively as low risk BCC using IGSRT and presents a viable alternative to MMS. The targeted approach using IGSRT, incorporating high resolution dermal ultrasound (HRDUS), appear to enhance treatment accuracy and effectiveness demonstrating high LC rates in all subtypes of BCC comparable to MMS and is a viable non-surgical option. Plain language summary Effectiveness of a non-surgical skin cancer treatment using an image guided form of radiation modality on all subtypes of basal cell skin cancerRecent studies using a non-surgical treatment combining low penetrance radiation with ultrasound called Image Guided Superficial Radiation Therapy (IGSRT) showed promise in curing Basal Cell Cancer (BCC) of the skin, which is the most common skin cancer worldwide afflicting millions annually. Recent studies on early stage (I, II) BCCs treated with IGSRT (estimated combined total of [~]1900 BCC cases) appear to rival the best surgical treatment available called Mohs Micrographic Surgery ("Mohs" or MMS). Furthermore, certain subtypes of BCC appear to behave more aggressively with worse outcomes even with surgery and is generally felt inappropriate for radiation treatment. However, BCC subtypes were not specified in previous IGSRT studies. This study presents the largest experience (using medical chart review) in approximately 8000 BCC cases treated by IGSRT across the continental United States separated by aggressive vs non-aggressive subtypes for early stages (I, II) as well as more advanced (stage III) BCC cases to evaluate the efficacy and safety. This study confirms the high cure/control rate and safety of IGSRT for all subtypes of BCC which appear equivalent with Mohs (although the study was not meant to be a head to head comparison of the 2 different modalities). Moreover, the aggressive types of BCC showed similar (if not marginally better) cure rates than the more common non-aggressive BCC subtypes. The potential benefits to patients from this study show there is now a clinically proven non-surgical treatment with the same effectiveness as surgery for the most common cancer on the planet. Key PointsO_LIThis study provides evidence that backs up using IGSRT as a viable treatment option to MMS for both high risk and non-high risk BCC cases, achieving similar local control rates for both groups. C_LIO_LIIt highlights that high risk BCC is more sensitive to radiation therapies such as IGSRT than previously believed, challenging the conventional practice of surgical treatment. C_LI

ObjectiveNrf2 overexpression confers poor prognosis in some cancers but its role in colorectal cancer (CRC) is unknown. Due to its role as a transcription factor we hypothesise a metagene of NRF2 regulated genes could act as a prognostic biomarker in CRC.\n\nDesignUsing known NRF2 regulated genes, we defined an NRF2 metagene to represent the pathway expression using principal component analysis and Cox proportional hazard models. The NRF2 metagene was validated in four independent datasets, including the recently profiled MRC FOCUS randomised controlled trial.\n\nResults36 genes comprised the final prognostic metagene in the training set. 1,360 patients were included in the validation analyses. High NRF2 metagene expression is associated with worse disease free survival (DFS) and overall survival (OS) outcomes in stage I/II/III disease and worse OS in stage IV disease. In multivariate analyses, NRF2 expression remained significant when adjusted for known prognostic factors of adjuvant chemotherapy and stage in stage I/II/III disease, as well as BRAF V600E mutation and sidedness in stage IV disease. NRF2 metagene expression exhibits variation within each of the Consensus Molecular Subtypes (CMS) but high expression is particularly enriched in CMS 4.\n\nConclusionWe demonstrate in a large scale analysis that NRF2 expression is a novel biomarker of poor prognosis across all stages of colorectal cancer. Higher expression observed in CMS 4 further refines the molecular taxonomy of colorectal cancer.

AimTo examine the adherence rate to surveillance guidelines after curative resection of colorectal cancer (CRC) and the impact of demographic factors. MethodsData was collected retrospectively including demographics, stage at diagnosis, and adherence to surveillance guidelines as recommended by the US Multi-Society Task Force (USMSTF) guidelines, for colorectal cancer (CRC) patients who underwent curative surgical resection between 2005 and 2014 in a tertiary academic medical center. ResultsA total of 124 patients were included (Male /female, 56.5%/ 43.5%), African American 109 (87.9%), and 70 patients (56.5%) had Medicare/Medicaid insurance. Overall, Appropriate clinical evaluation twice per year for 3 years following surgery was completed in 78 (63%) of patients. A total of 56 (45%) had carcinoembryonic antigen (CEA) levels checked twice a year for 3 years. Surveillance colonoscopy 1 year postoperatively occurred in 64 (51.6%), and 37 (29.8%) had a second colonoscopy 3 years postoperatively. Abdomen/pelvis CT scan was obtained in 90 (72.5%) at 1 year post-operatively. In the entire cohort, strict adherence to post-recession surveillance only occurred in 46 (37.1%). There was no correlation between adherence to surveillance and gender (p=0.184), race (p=0.118), or insurance type (p=0.51). ConclusionAdherence to surveillance after curative resection of CRC was inadequate regardless of socioeconomic, medical insurance, or race. Measures should be taken to identify barriers and improve compliance with guidelines. What is already known on this topic?Effective surveillance after colorectal cancer surgery is essential, yet many patients fail to follow recommended guidelines. Existing research highlights disparities in CRC outcomes based on race, socioeconomic status, and insurance coverage, affecting early detection and treatment. What this study addsOur study reveals a 37.1% adherence rate to surveillance guidelines among CRC patients in an urban medical center, unaffected by gender, race, or insurance status. This challenges previous assumptions about demographic disparities in post-resection care. How this study might affect research, practice, or policyThe study highlights the need for interventions to improve adherence rate to CRC surveillance. Future research, clinical practices, and policy initiatives should focus on overcoming barriers to ensure equitable and effective follow-up care.

Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in humans and kills as many people annually as melanoma. The mutational and transcriptional landscape of cSCC has identified driver mutations associated with disease progression as well as key pathway activation in the progression of pre-cancerous lesions. The understanding of the transcriptional changes with respect to high-risk clinical/histopathological features and outcome is poor. Here, we examine stage-matched, outcome-differentiated cSCC and associated clinicopathologic risk factors using whole exome and transcriptome sequencing on matched samples. Exome analysis identified key driver mutations including TP53, CDKN2A, NOTCH1, SHC4, MIIP, CNOT1, C17orf66, LPHN22, and TTC16 and pathway enrichment of driver mutations in replicative senescence, cellular response to UV, cell-cell adhesion, and cell cycle. Transcriptomic analysis identified pathway enrichment of immune signaling/inflammation, cell-cycle pathways, extracellular matrix function, and chromatin function. Our integrative analysis identified 183 critical genes in carcinogenesis and were used to develop a gene expression panel (GEP) model for cSCC. Three outcome-related gene clusters included those involved in keratinization, cell division, and metabolism. We found 16 genes were predictive of metastasis (Risk score [&ge;] 9 Met & Risk score < 9 NoMet). The Risk score has an AUC of 97.1% (95% CI: 93.5% - 100%), sensitivity 95.5%, specificity 85.7%, and overall accuracy of 90%. Eleven genes were chosen to generate the risk score for Overall Survival (OS). The Harrells C-statistic to predict OS is 80.8%. With each risk score increase, the risk of death increases by 2.47 (HR: 2.47, 95% CI: 1.64-3.74; p<0.001) after adjusting for age, immunosuppressant use, and metastasis status.

Breast cancer shows plasticity in terms of classification. Upon drug treatment and metastasis some tumors switch to another subtype leading to loss of response to therapy. In this study, we ask the question which molecular subclasses of breast cancer are more switchable upon drug therapy and metastasis. We used in silico data to classify breast cancer tumors in PAM50 molecular classes before treatment and after treatment using gene expression data. Similar analysis was performed for primary tumors and their metastatic growth. Our analysis showed that in both scenarios some breast tumors shift from one class to another. This suggests that patients who underwent chemotherapy but resulted in relapse or/and metastasis should be retyped for molecular subclass so that treatment protocol should be adopted according to those subtypes. Additionally, 20 genes were identified as biomarkers for metastasis in breast cancer.

BackgroundSome pancreatic cancer patients for curative-intent surgery are found to actually have unresectable disease on laparotomy. This systematic review aimed to identify parameters that can potentially help predict intraoperative resectability status. MethodsLiterature search was done across PubMed, Scopus, Web of Science, and Cochrane Library to identify studies since 2011 assessing for independent association of preoperative parameters with intraoperative pancreatic cancer resectability. Parameters investigated by at least two studies were identified. For discordant findings, meta-analyses using the random effects model were done, incorporating studies that can be pooled. Pooled odds ratios and mean differences were obtained for parameters with binary and continuous values, respectively, with 95% confidence intervals. Subgroup analyses were done for significant heterogeneity. ResultsFrom initially 8,959 articles searched, 18 studies were included, with 13 parameters identified for synthesis. Elevated serum CA19-9 (>35-1000 U/mL) and larger tumor size (>22-40 mm) were shown to independently predict intraoperative unresectability in the most number of studies. For parameters subjected to meta-analyses, abdominal pain, weight loss, lower body mass index (BMI), lower serum transaminases, and preoperative borderline resectability were significantly associated with intraoperative unresectability, while age and sex were not. Subgroup analyses addressing heterogeneity revealed that tumor location in the pancreatic body/tail is significantly associated with actual unresectability whereas poorer performance status was not. Other parameters shown to have predictive value but could not be included in meta-analyses are serum CA125 and imaging-to-surgery time interval. ConclusionSynthesis of studies has shown that elevated serum CA19-9 and larger tumors are independently associated with intraoperative pancreatic cancer unresectability. Other predictive factors include abdominal pain, weight loss, lower BMI, lower serum transaminases, preoperative borderline resectability, and tumor location in the pancreatic body/tail. Staging laparoscopy or neoadjuvant therapy should be considered for potentially resectable pancreatic cancer patients with these attributes. What is already known on this topicAccurate identification of patients with actual resectable pancreatic cancer remains challenging despite resectability criteria. Some parameters beyond resectability criteria have been found to offer clues regarding actual resectability. What this study addsSynthesis of studies has determined which clinical, laboratory, and radiologic parameters outside of resectability criteria may predict intraoperative resectability among pancreatic cancer patients being considered for curative-intent surgery. How this study might affect research, practice, or policyThe findings in this study may aid in deciding which pancreatic cancer patients should undergo staging laparoscopy first instead of directly attempting curative surgery. Research gaps have also been identified.

Pancreatic ductal adenocarcinoma (PDAC) prognosis and treatment response remains devastatingly poor due partly to the highly heterogeneous, aggressive, and immunosuppressive nature of this tumor type. The intricate relationship between stroma, inflammation, and immunity remains vaguely understood in the PDAC microenvironment. Here, we performed a meta-analysis of stroma-, and immune-related gene expression in the PDAC microenvironment to improve disease prognosis and therapeutic development. We selected twenty-one PDAC studies from the Gene Expression Omnibus and ArrayExpress databases, including 922 samples (320 controls and 602 cases). Differential gene enrichment analysis identified 1153 significant dysregulated genes in PDAC patients that contribute to a desmoplastic stroma and an immunosuppressive environment (the hallmarks of PDAC tumors). The results highlighted two gene signatures related to the immune and stromal environments that cluster PDAC patients in high- and low-risk groups, impacting patient stratification and therapeutic decision-making. Moreover, HCP5, SLFN13, IRF9, IFIT2, and IFI35 immune genes were related to prognosis value in PDAC patients, for the first time. Simple SummaryPancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with few curative options. Desmoplastic stroma and immune system evasion in PDAC represent challenges to the success of therapeutic strategies that function well in other tumor types. Characterizing the PDAC microenvironment (including the immune environment) remains critical to developing safe and efficient therapies. Here, we present a comprehensive meta-analysis identifying 1153 significantly dysregulated genes, which mainly impact extracellular matrix remodeling and the immune system. We identify two signatures of twenty-eight immune-related genes and eleven stroma-related genes influencing PDAC patient survival. Additionally, five immune genes are associated with PDAC prognosis for the first time.

Objective: The relationship between the waiting time of postoperative radiotherapy and the prognosis of patients with high-grade glioma is still inconclusive, and we addressed this issue through a systematic review and meta-analysis. Methods: Twenty studies published between 1975 and 2019 about waiting times (WT) of radiotherapy with high-grade glioma were retrieved for meta-analysis.The meta-analysis was performed by converting the effect sizes of different WT into regression coefficients ({beta}) and standard error (SE) to indicate the daily impact of delay on OS. Results: A total of 8462 high-grade glioma patients were included in the 20 studies, and no correlation between WT delay and OS was found in the unadjusted model through meta-analysis (HR=1, 95%CI=0.99-1.01, p=0.962). Meta-regression was used to adjust for other prognostic factors and no clear evidence of the relationship between WT delay and OS was found. Conclusion: This meta-analysis suggests that there is no clear evidence for the effect of delayed radiotherapy on OS with high-grade glioma patients.

Purpose The Karolinska Liver Metastases (KaroLiver) cohort was established to investigate associations between clinical characteristics and histopathological features in patients treated with curative intent for colorectal cancer liver metastases (CRLM). The cohort combines whole-slide digital histopathology images with detailed oncological, surgical, radiological and survival data, enabling comprehensive analyses of treatment trajectories, clinical outcomes and metastatic tumour biology. Participants KaroLiver is a retrospective observational cohort comprising all consecutive patients who received curative-intent, liver-directed treatment for CRLM at Karolinska University Hospital in Stockholm, Sweden. The hospital is the primary regional referral centre for HPB surgery, serving the population of approximately 2.5 million people in the Stockholm-Gotland healthcare region. Patient enrolment is continuously updated in accordance with amended ethical approvals and evolving scientific questions. The cohort currently comprises 811 patients who underwent 1204 liver interventions between February 2012 and January 2022. Detailed clinical, oncological, surgical, pathological, molecular, recurrence and survival data are collected. Findings to date Median overall survival (OS) in the current cohort is 51.0 months (95% CI 46.2-57.1 months), and median recurrence-free survival (RFS) is 10.4 months (95% CI 9.2-11.9 months). The five-year OS rate is 44.9% (95% CI 41.2-48.8%). Studies using the cohort have so far identified a liver injury-derived stromal capsule in a subset of metastases, associated with improved survival. The cohort has also enabled the identification of histopathological markers of tumour biology, sex-based differences in treatment and survival, and associations between post-hepatectomy liver failure and oncological outcomes. Future plans Current research priorities include advanced histology-based prognostic scoring, sex differences in recurrence and retreatment, tumour biology and outcomes in early-onset versus average-onset CRLM, as well as CT- and MRI-based radiomics, all integrated within KaroLiver's histopathological framework. Data sharing is supported, given that regulatory requirements are met. Retrospective accrual and outcome updates will continue for current and future studies, subject to the required approvals.

This review summarizes the immunohistochemical profiles of dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) as reported by primary literature in the past 10 years. 63 studies were included in the review, with staining information for a total of 99 unique IHC markers reported. The most commonly reported stains were CD34, SMA, S100, and FXIIIa. Most studies applied IHC either to explore descriptive features of DF or DFSP or to determine their utility in diagnostic identification of the lesions. A number of studies applied novel biomarkers which may hold promise for distinguishing DF and DFSP, namely WT1, Cx43, LSP-1, and PHH3, which demonstrated considerable expression differences between the two lesions. This review highlights the need for validation of existing and emerging IHC markers for the diagnosis of DF and DFSP.

BACKGROUNDIdentifying the molecular subtypes of breast cancer (BC) plays a crucial role in enhancing the efficacy of therapy. MiRNAs (miRs) with differential expressions in different subtypes of breast tumors can be considered as non-invasive biomarkers for diagnosing BC subtypes. OBJECTIVEWe aimed to investigate the efficacy of miR-190b, miR-584-5p, miR-452-5p, and miR-1306-5p as novel potent diagnostic biomarkers in discriminating patients with luminal (ER+) and non-luminal (ER-) BCs. METHODSA group of miRs significantly associated with estrogen cell receptors (ER) in breast tumors were identified using feature selection methods analysis on miR-Seq datasets retrieved from TCGA and GSE68085. Four abovementioned miRs were selected as novel potential biomarkers, and their relative expression levels were assessed within adjacent non-tumor, ER+ and ER- tumor tissues by quantitative RT-PCR. Their impact on diagnosis was also evaluated by ROC curve analysis. RESULTSIn ER+ BCs compared to ER- BCs, the expression of miR-190b was remarkably increased, while the expression of miR-584-5p, miR-452-5p, and miR-1306-5p were significantly decreased. This group could discriminate ER+ and ER- BCs at an AUC of 0.973. CONCLUSIONSAccording to our findings, these four miRs are promising biomarkers in discriminating BC subtypes. The candidate miRs in parallel with histologic diagnosis methods can be applied for identifying patients who are most likely responding to specific therapies based on ER status.

Cancer-type-specific molecular alterations often reflect the unique biological context of their tissue of origin and are more likely to represent relevant drivers rather than passenger events. We analyzed data from The Cancer Genome Atlas (TCGA) spanning 39 cancer types and 6 molecular platforms to create a comprehensive atlas of cancer-type-specific molecular features through unified comparative analyses. Simple nucleotide variation analysis characterized cancer-type-specific gene mutations and revealed heterogeneity among mutated genes within shared pathways. Copy number variation analysis characterized cancer-type-specific amplifications and deletions and demonstrated synergistic interactions between gene deletions and mutations. DNA methylation analysis identified candidate hypermethylated genes alongside well-established targets. Transcriptome profiling analysis revealed cancer-type-specific pathway enrichment reflecting tissue-of-origin functions or novel associations. Multiomics clustering analysis identified multi-cancer clusters and revealed consistent patterns across molecular platforms. These findings provide insights into cancer-type-specific molecular features and offer comprehensive visualizations as a reference resource for clinical application and hypothesis generation.

miRNAs are small non-coding RNAs that regulate most cellular processes. Tumorigenesis disrupts the normal balance in the cell, which leads to changes in the cell cycle, cell signalling, activation of growth factors, miRNA deregulation, etc. Thus, the variations in miRNA expression between normal and tumor stages can be used to predict, diagnose, detect and identify different cancer stages, thereby suggesting the potential use of the miRNAs as biomarkers or potential therapeutic targets for cancer. In this study we aim to identify differentially expressed miRNAs which could serve as potential biomarkers or therapeutic targets for breast cancer. Microarray-based expression analysis was performed on tissue samples from patients with early and locally advanced breast cancer and nCounter analysis was performed to detect differentially expressed miRNA. Additionally, functional enrichment analysis, miRNA linked gene prediction, and in silico analysis for miRNA expression in cancer databases were carried out. This analysis revealed increased expression of Hsa-miR-199a and b. Further these miRs had increased expression levels across various cancer. Importantly, genes such as CALR, SSR2, and YWHAZ predicted as miRs target were highly expressed in breast cancer. However, these genes lack therapeutic drugs targeting them. Overall, our study identified previously unexplored miRNAs and their gene targets, which could be exploited as potential targets for future therapeutic interventions.