肝细胞癌中高RPS11水平与根治性切除术后预后不良相关。
High RPS11 level in hepatocellular carcinoma associates with poor prognosis after curative resection.
作者信息
Zhou Chenhao, Sun Jialei, Zheng Zhiyuan, Weng Jialei, Atyah Manar, Zhou Qiang, Chen Wanyong, Zhang Yuan, Huang Jiaxing, Yin Yirui, Mao Huarong, Zhang Ziping, Yi Yong, Ren Ning
机构信息
Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China.
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
出版信息
Ann Transl Med. 2020 Apr;8(7):466. doi: 10.21037/atm.2020.03.92.
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.
背景
核糖体蛋白S11（RPS11）是核糖体蛋白家族的成员，据报道在多种恶性肿瘤中过表达，并与肿瘤复发相关。然而，我们目前对RPS11在肝细胞癌（HCC）中的了解仍然有限。在本研究中，我们将探讨RPS11在根治性切除术后HCC患者中的潜在预后价值。
方法
采用免疫组织化学（IHC）方法评估复旦大学附属中山医院182例HCC患者的训练队列和90例HCC患者的验证队列中组织芯片上RPS11的表达。还使用蛋白质免疫印迹法和定量逆转录PCR（qRT-PCR）来测定RPS11在肝癌细胞系中的表达水平。进一步构建两个列线图、校准曲线和决策曲线分析（DCA），以评估RPS11水平预测HCC患者临床结局的性能。此外，在TCGA肝癌数据库中进行单样本基因集富集分析（ssGSEA），以研究RPS11涉及的潜在生物学途径。
结果
与正常肝细胞相比，大多数HCC细胞系中均观察到RPS11的mRNA和蛋白质水平升高，且肿瘤RPS11水平高与根治性切除术后HCC患者的总生存期（OS）和无复发生存期（RFS）缩短相关。单因素和多因素分析表明，RPS11是HCC的独立预后因素。进一步构建了两个列线图、校准曲线和DCA曲线，显示出对OS和RFS具有更高的预后准确性，并且在HCC中比传统分期系统具有更多的临床益处。此外，通过ssGSEA在高RPS11表达中富集了几种与肿瘤耐药性、生存和复发相关的途径和分子。
结论
肿瘤RPS11是接受根治性切除的HCC患者的潜在预后生物标志物。
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