High RPS11 level in hepatocellular carcinoma associates with poor prognosis after curative resection

BACKGROUND: Ribosomal protein S11 (RPS11), a member of ribosomal protein family, is reported to overexpress in diverse malignancies and correlates with tumor recurrence. However, our current knowledge on RPS11 in hepatocellular carcinoma (HCC) remains limited. In this study, we are going to explore the potential prognostic value of RPS11 in HCC patients after curative resection. METHODS: Immunohistochemistry (IHC) was performed to evaluate RPS11 expression on tissue microarrays in training cohort comprising 182 HCC patients and validation cohort enrolling 90 HCC patients in Zhongshan Hospital, Fudan University. Western blot and quantitative reverse transcription PCR (qRT-PCR) were also used to determine the expression level of RPS11 in liver cell lines. Two nomograms, calibration curves and decision curve analysis (DCA) were further performed to assess the performance of RPS11 level in predicting clinical outcomes of HCC patients. Additionally, single-sample gene-set enrichment analysis (ssGSEA) was conducted in TCGA liver cancer database to investigate the potential biological pathways involved in RPS11. RESULTS: Both increased mRNA and protein levels of RPS11 were observed in most HCC cell lines when compared to the normal hepatocytes, and high tumor RPS11 level was associated with shorter overall survival (OS) and recurrence-free survival (RFS) of HCC patients after curative resection. Univariate and multivariate analysis indicated that RPS11 was an independent prognostic factor in HCC. Two nomograms, calibration and DCA curves were further established and displayed a superior prognostic accuracy of OS and RFS, and showed more clinical benefits than traditional staging systems in HCC. Furthermore, several pathways and molecules related to tumor resistance, survival and recurrence were enriched in high RPS11 expression by ssGSEA. CONCLUSIONS: Tumorous RPS11 acts as a potential prognostic biomarker for HCC patients who received curative resection.