跨膜蛋白201在肝细胞癌中的表达及其预后意义与作用机制

背景与目的 研究发现跨膜蛋白（TMEM）家族基因与肿瘤关系密切，TMEM201是TMEM家族的一员，其在肝细胞癌（HCC）中的表达与作用目前尚不清楚。因此，本研究通过生物信息学方法分析TMEM201在HCC中的表达与作用，并预测其在HCC中可能作用的通路，进而探讨机制。方法 在TIMER中分析TMEM201在泛癌中的表达。下载TCGA与GEO数据库中HCC患者数据，并收集106例HCC患者的手术标本与临床信息，分析TMEM201在肝癌组织与癌旁组织中的表达情况，并绘制生存曲线，分析TMEM201表达与HCC患者的预后关系。用单因素与多因素Cox分析判断HCC相关危险因素。根据TCGA与临床数据，分析TMEM201的表达与HCC患者临床病理特征的关系。应用String和GeneMANIA数据库绘制与TMEM201及其相关基因的网络图谱。通过TCGA数据库分析TMEM201与免疫细胞的关系。通过LinkedOmics数据库分析与TMEM201相关的共表达基因，并对共表达基因进行GO功能分析与KEGG通路预测。结果 泛癌分析结果显示，TMEM201在绝大部分肿瘤中呈高表达。多数据库及临床HCC标本免疫组化分析显示，TMEM201在HCC组织中的表达明显高于癌旁组织（均P<0.05），且TMEM201高表达患者生存时间明显短于低表达患者。单因素与多因素Cox风险回归提示TMEM201的表达是HCC患者总体生存率的独立危险因素。蛋白质互作网络、GeneMANIA数据库分析显示，TMEM201与SUN1、SUN2、LMNB1、EMD等基因存在明显相互作用。免疫浸润分析结果显示，TMEM201表达与树突状细胞、细胞毒性细胞、Th2细胞等明显有关。此外，功能富集分析显示，TMEM201与共表达基因参与了许多HCC的生物学过程、细胞组成、分子功能和作用通路。通路结果及相关性热图提示TMEM201与细胞周期高度相关。结论 TMEM201在HCC组织中高表达，是影响HCC患者预后的独立危险因素，TMEM201在HCC中的作用机制可能与免疫浸润的调节、细胞周期的调控有关。

Expression and of transmembrane protein 201 in hepatocellular carcinoma and its prognostic significance and action mechanism

Background and Aims Research has found a close relationship between transmembrane protein (TMEM) family genes and tumors. TMEM201 is a member of the TMEM family, and its expression and role in hepatocellular carcinoma (HCC) are currently unclear. Therefore, this study was conducted, uses bioinformatics methods, to analyze the expression and function of TMEM201 in HCC and predict the pathways it may be involved in, exploring the underlying mechanisms.Methods TMEM201 expression in pan-cancer is analyzed using TIMER. Data of HCC patients from TCGA and GEO databases are downloaded, and the specimens and clinical information of 106 HCC patients were collected. The expressions of TMEM201 in liver cancer tissue and adjacent tissue were analyzed, the survival curves were plotted to analyze the relationship between TMEM201 expression and the prognosis of HCC patients. Univariate and multivariate Cox analyses are employed to identify HCC-related risk factors. The relationship between TMEM201 expression and clinicopathologic characteristics of HCC patients was analyzed based on TCGA and clinical data. String and GeneMANIA databases were used to construct a network diagram of TMEM201 and its related genes. TCGA database was used to analyze the relationship between TMEM201 and immune cells. LinkedOmics database was employed to analyze co-expressed genes related to TMEM201, followed by GO functional analysis and KEGG pathway prediction of these co-expressed genes.Results Pan-cancer analysis showed that TMEM201 was highly expressed in the majority of tumors. Multiple databases analysis and immunohistochemical results of clinical HCC specimens revealed that TMEM201 expression in HCC tissue was significantly higher than that in adjacent tissue (all P<0.05). Additionally, patients with high TMEM201 expression had a significantly shorter survival time than those with its low expression. Univariate and multivariate Cox regression suggested that TMEM201 expression was an independent risk factor for overall survival in HCC patients. Protein interaction networks and GeneMANIA database analysis showed significant interactions between TMEM201 and genes such as SUN1, SUN2, LMNB1, and EMD. Immune infiltration analysis indicated a significant association between TMEM201 expression and dendritic cells, cytotoxic cells, Th2 cells, etc. Furthermore, functional enrichment analysis demonstrated that TMEM201 and its co-expressed genes were involved in various biological processes, cellular components, molecular functions, and signaling pathways related to HCC. Pathway results and correlation heatmaps suggested a strong correlation between TMEM201 and the cell cycle.Conclusion TMEM201 is highly expressed in HCC tissue and is an independent risk factor influencing the prognosis of HCC patients. The mechanism of action of TMEM201 in HCC may be related to the regulation of immune infiltration and the control of the cell cycle.