Intratumor bacteria is associated with prognosis in clear-cell renal cell carcinoma

BackgroundIntratumor bacteria (ITB) plays a role in various cancer types. Its role in clear-cell renal cell carcinoma (ccRCC) remains elusive due to small sample size and inadequate decontamination in relevant studies. ObjectiveTo establish common and reproducible ITB-associated biomarkers in ccRCC. Design, setting, and participantsThis retrospective study comprised seven bulk RNA sequencing datasets from six publicly available cohorts and one in-house Chinese cohort (Renji), one 16S rRNA sequencing dataset from an original Chinese cohort (Huashan), and one publicly available single-cell RNA sequencing dataset. All of these datasets included ccRCC cases. Outcome measurements and statistical analysisComposition was presented by relative abundance. Overall and progression-free survival were primary outcomes profiled by putative ITB load and risk score, respectively. Potential host interaction was exploratorily analyzed using gene set enrichment analysis and Sparse CCA. Results and limitationsNine cohorts encompassing a total of 1049 ccRCC cases and 130 paired normal tissues were initially analyzed and underwent decontamination. Surprisingly, neither diversity nor composition was differentially distributed between normal and cancer tissue. High putative bacterial load was associated with better overall survival. Notably, a 7-genera dichotomized ITB risk score was indicative of overall survival and a 13-genera dichotomized ITB risk score was predictive of progression-free survival, respectively. Actinomyces, Rothia and Bifidobacterium showed a protective role while Exiguobacterium was a risk factor. A limitation is lack of causation analyses. ConclusionsITB exists in ccRCC. High ITB loads and ITB-risk score predicts better ccRCC survival regardless of sequencing tech, sample processing or racial disparity. Patient SummaryIn this report, we explored the role of intratumor bacteria (ITB) in renal clear-cell carcinoma (ccRCC) in patients with different race and sequencing platforms. Putative ITB load and a 7-genera ITB risk score were associated with overall survival. A 13-genera ITB risk score was predictive of progression-free survival. We conclude that certain ITB features are universally pathogenic to ccRCC.