Pan Junhan, Zhang Cong, Sa Guo, Huang Huizhen, Zhang Rui, Chen Feng
Department of Radiology, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, China.
Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, China.
Asian J Surg. 2024 Jul 9. doi: 10.1016/j.asjsur.2024.06.097.
Recent studies show that ribosomal protein S21 (RPS21) plays a role in the development and progression of various malignancies. However, the biological value of RPS21 in hepatocellular carcinoma (HCC) and its association with immunotherapy remain unknown.
Here, we examined the differential expression of RPS21 between HCC and normal liver tissues, using the TCGA, ICGC and GEO databases, followed by verification by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) in LO2, SMMC7721, HepG2, and MHCC-97H cell lines. Kaplan-Meier and Cox regression analyses were applied to investigate how RPS21 expression influenced overall survival, and a nomogram was established to predict prognosis among HCC patients. We further analyzed how RPS21 expression was related to tumor immune microenvironment, immunotherapy efficiency, and genomic alterations, and investigated potential underlying mechanisms.
RPS21 upregulation was observed in HCC tissues and cell lines, compared to normal controls. Survival analysis revealed that RPS21 overexpression was significantly associated with poor clinical outcomes (all p < 0.05). Functional enrichment analyses indicated that differentially expressed genes relative to RPS21 expression were mainly involved in tumor response, proliferation, and metabolism. Additionally, RPS21 expression was positively correlated with the infiltration of activated CD4 T cells and tumor mutational burden (all p < 0.05). Moreover, RPS21 was co-expressed with immune-related genes and immune checkpoint genes. Analyses of drug sensitivity predict that HCC patients with low RPS21 expression were more sensitive to targeted immunotherapy.
The present results suggested that RPS21 might be a promising prognostic marker and a potential immunotherapy target for patients with HCC.
近期研究表明，核糖体蛋白S21（RPS21）在多种恶性肿瘤的发生和发展中发挥作用。然而，RPS21在肝细胞癌（HCC）中的生物学价值及其与免疫治疗的关系仍不清楚。
在此，我们利用TCGA、ICGC和GEO数据库检测了HCC与正常肝组织中RPS21的差异表达，随后通过逆转录定量聚合酶链反应（RT-qPCR）在LO2、SMMC7721、HepG2和MHCC-97H细胞系中进行验证。应用Kaplan-Meier和Cox回归分析来研究RPS21表达如何影响总生存期，并建立列线图以预测HCC患者的预后。我们进一步分析了RPS21表达与肿瘤免疫微环境、免疫治疗疗效和基因组改变的关系，并研究了潜在的机制。
与正常对照相比，在HCC组织和细胞系中观察到RPS21上调。生存分析显示，RPS21过表达与不良临床结局显著相关（所有p<0.05）。功能富集分析表明，与RPS21表达相关的差异表达基因主要参与肿瘤反应、增殖和代谢。此外，RPS21表达与活化的CD4 T细胞浸润和肿瘤突变负荷呈正相关（所有p<0.05）。此外，RPS21与免疫相关基因和免疫检查点基因共表达。药物敏感性分析预测，RPS21表达低的HCC患者对靶向免疫治疗更敏感。
目前的结果表明，RPS21可能是HCC患者有前景的预后标志物和潜在的免疫治疗靶点。
