Chen Liang, Lin Yunhua, Liu Guoqing, Xu Rubin, Hu Yiming, Xie Jiaheng, Yu Hongzhu
Department of General Surgery, Fuyang Hospital Affiliated to Anhui Medical University, Fuyang, Anhui, People's Republic of China.
The First Clinical Medical College, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
Int J Gen Med. 2021 Oct 30;14:7435-7451. doi: 10.2147/IJGM.S336725. eCollection 2021.
Hepatocellular Carcinoma (HCC) has the characteristics of high incidence and poor prognosis. However, the underlying mechanism of HCC has not yet been fully elucidated. This study aims to investigate the potential mechanism and clinical significance of signal sequence receptor (SSR1) in HCC through bioinformatics methods.
Four online (GEPIA, TIMER, TCGA, and GEO) databases were used to explore the expression level of SSR1 in HCC. The summary receiver operating characteristic (SROC) analysis and standardized mean difference (SMD) calculation were performed further to detect its diagnostic ability and expression level. The Human Protein Atlas (HPA) database was applied to verify the level of SSR1 protein expression. Chi-square test and Fisher's exact test were carried out to determine the clinical relevance of SSR1 expression. KM survival analysis, univariate and multivariate COX regression analyses were employed to explore the prognostic impact of SSR1. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene set enrichment analysis (GSEA) were implemented to reveal the underlying mechanism of SSR1. Quantitative Real-Time Polymerase Chain Reaction (QRT-PCR) was used to verify the expression of SSR1 in HCC.
SSR1 was significantly overexpressed in HCC (SMD=1.25, =0.03) and had the moderate diagnostic ability (AUC=0.84). SSR1 expression was significantly correlated with T stage, Gender, Pathologic stage (All <0.05). Patients with high SSR1 expression had shorter overall survival (OS). Univariate and multivariate Cox regression analyses showed that high SSR1 expression was an independent risk factor for poor prognosis. KEGG analysis showed that SSR1-related genes were enriched in the cell cycle, DNA replication, and TGF-beta signaling pathway. GSEA analysis also shows that the high expression of SSR1 is related to the activation of the above three signal pathways. qRT-PCR showed that the SSR1 expression in HCC was significantly higher than the Peri-carcinoma tissue (PHCC) and the corresponding normal liver tissue.
SSR1 expression was significantly up-regulated, and it had the potential as a biomarker for the diagnosis and prognosis of HCC. It was very likely to participate in the occurrence and development of HCC by regulating the cell cycle. In summary, our study comprehensively analyzed the clinical value of SSR1 and also conducted a preliminary study on its potential mechanism, which will provide inspiration for the in-depth study of SSR1 in HCC.
肝细胞癌（HCC）具有高发病率和预后差的特点。然而，HCC的潜在机制尚未完全阐明。本研究旨在通过生物信息学方法探讨信号序列受体（SSR1）在HCC中的潜在机制及临床意义。
使用四个在线（GEPIA、TIMER、TCGA和GEO）数据库来探究SSR1在HCC中的表达水平。进一步进行汇总接受者操作特征（SROC）分析和标准化均数差（SMD）计算，以检测其诊断能力和表达水平。应用人类蛋白质图谱（HPA）数据库验证SSR1蛋白表达水平。进行卡方检验和Fisher精确检验以确定SSR1表达的临床相关性。采用KM生存分析、单因素和多因素COX回归分析来探讨SSR1的预后影响。实施京都基因与基因组百科全书（KEGG）分析和基因集富集分析（GSEA）以揭示SSR1的潜在机制。使用定量实时聚合酶链反应（QRT-PCR）验证SSR1在HCC中的表达。
SSR1在HCC中显著过表达（SMD = 1.25，P = 0.03），并具有中等诊断能力（AUC = 0.84）。SSR1表达与T分期、性别、病理分期显著相关（均P < 0.05）。SSR1高表达的患者总生存期（OS）较短。单因素和多因素Cox回归分析表明，SSR1高表达是预后不良的独立危险因素。KEGG分析表明，与SSR1相关的基因富集在细胞周期、DNA复制和转化生长因子-β信号通路中。GSEA分析还表明，SSR1的高表达与上述三个信号通路的激活有关。qRT-PCR显示，HCC中SSR1的表达显著高于癌旁组织（PHCC）和相应的正常肝组织。
SSR1表达显著上调，具有作为HCC诊断和预后生物标志物的潜力。它很可能通过调节细胞周期参与HCC的发生和发展。总之，我们的研究全面分析了SSR1的临床价值，并对其潜在机制进行了初步研究，这将为深入研究SSR1在HCC中的作用提供启示。
