Xiao Qingyu, Qu Weixiang, Shen Wenying, Cheng Zhen, Wu Haijun
Department of Blood Transfusion, Shenzhen Baoan Shiyan People's Hospital, Shenzhen, China.
Department of Gastroenterology, Shenzhen Baoan Shiyan People's Hospital, Shenzhen, China.
Transl Cancer Res. 2024 Oct 31;13(10):5278-5299. doi: 10.21037/tcr-24-277. Epub 2024 Oct 29.
Although signal sequence receptor subunit 1 (SSR1) has undergone thorough examination in different cancer types, its importance in hepatocellular carcinoma (HCC) remains largely uncharted and warrants further investigation. The aim of this study is to explore the role of SSR1 in HCC progression and to decipher its underlying molecular mechanisms.
We employed the ONCOMINE, Tumor IMmune Estimation Resource (TIMER), and The Cancer Genome Atlas databases to assess SSR1 expression levels within tumor tissues. Logistic and Cox regression analyses, Kaplan-Meier survival plots, nomograms, and forest plots were employed to establish correlation between SSR1 and prognosis. Receiver operating characteristic (ROC) curves demonstrated diagnostic utility of SSR1. Additionally, Gene Ontology (GO) and gene set enrichment analysis (GSEA) analyses were conducted to uncover relevant molecular pathways. TIMER was instrumental in elucidating the connection between SSR1 and immune cell infiltration. Actions of SSR1 in HCC proliferation and migration were investigated through quantitative real-time polymerase chain reaction, Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine cell proliferation assays, and Transwell migration and wound healing experiments.
Elevated SSR1 levels were found to be correlated with clinical parameters such as age and pathologic stage, thereby predicting a reduced overall survival (OS) rate in HCC patients. Multivariate survival analysis underscored SSR1 as an independent prognostic marker for OS. A nomogram underscored SSR1's effectiveness as a predictive tool for HCC outcomes, while ROC analysis indicated its high diagnostic accuracy. GO and GSEA analyses suggested that elevated SSR1 expression may be associated with epithelial-mesenchymal transition (EMT) pathway. SSR1 exhibited a negative correlation with cytotoxic cells and a positive correlation with Th2 cells. Our experiments provided evidence that heightened SSR1 levels may impact HCC proliferation and migration through EMT pathway.
SSR1 surfaces as a new diagnostic and potentially prognostic biomarker, showing an association with immune cell infiltration and cell proliferation in HCC.
尽管信号序列受体亚基1（SSR1）已在不同癌症类型中得到深入研究，但其在肝细胞癌（HCC）中的重要性在很大程度上仍不明确，值得进一步研究。本研究旨在探讨SSR1在HCC进展中的作用，并阐明其潜在的分子机制。
我们利用ONCOMINE、肿瘤免疫评估资源（TIMER）和癌症基因组图谱数据库来评估肿瘤组织内SSR1的表达水平。采用逻辑回归和Cox回归分析、Kaplan-Meier生存曲线、列线图和森林图来确定SSR1与预后之间的相关性。受试者工作特征（ROC）曲线显示了SSR1的诊断效用。此外，进行了基因本体（GO）和基因集富集分析（GSEA）以揭示相关的分子途径。TIMER有助于阐明SSR1与免疫细胞浸润之间的联系。通过定量实时聚合酶链反应、细胞计数试剂盒-8、5-乙炔基-2'-脱氧尿苷细胞增殖试验以及Transwell迁移和伤口愈合实验，研究了SSR1在HCC增殖和迁移中的作用。
发现SSR1水平升高与年龄和病理分期等临床参数相关，从而预测HCC患者的总生存率（OS）降低。多因素生存分析强调SSR1是OS的独立预后标志物。列线图强调了SSR1作为HCC预后预测工具的有效性，而ROC分析表明其具有较高的诊断准确性。GO和GSEA分析表明，SSR1表达升高可能与上皮-间质转化（EMT）途径有关。SSR1与细胞毒性细胞呈负相关，与Th2细胞呈正相关。我们的实验提供了证据，表明SSR1水平升高可能通过EMT途径影响HCC的增殖和迁移。
SSR1是一种新的诊断和潜在的预后生物标志物，显示出与HCC中的免疫细胞浸润和细胞增殖相关。
