TM4SF19——一种新的膀胱尿路上皮癌诊断和预后的生物标志物

TM4SF19—A New Biomarker for Diagnosis and Prognosis of Bladder Urothelial Carcinoma

摘要: 近年来科学研究证实四次跨膜L6超家族中的TM4SF19在肿瘤的发生、发展中发挥着重要作用，但TM4SF19在膀胱尿路上皮癌(BLCA)中的预后和免疫侵袭中的作用仍不清楚。本研究探讨TM4SF19在肿瘤组织中的表达及其与免疫侵袭的关系，并确定其在BLCA患者中的预后作用。本研究从癌症基因组图谱(TCGA)数据库中获取了患者的表达谱和临床信息。Mann-Whitney U检验(Wilcoxon秩和检验)分析BLCA中TM4SF19的差异表达。通过功能富集分析以探索所涉及的潜在信号通路和生物学功能。使用单样本基因集富集分析评估免疫细胞浸润。采用Kaplan-Meier法和Cox回归分析来确定TM4SF19的预后价值。构建列线图来预测癌症诊断后1年、5年和10年的总生存(OS)率。结果：TM4SF19在BLCA中过度表达。TM4SF19高表达组中多条途径被显著富集，其中不乏多条肿瘤相关途径及免疫相关途径。TM4SF19表达与巨噬细胞、Th1细胞和其他免疫细胞呈正相关，但与NKCD56bright细胞和肥大细胞呈负相关。TM4SF19的表达水平与T分期、N分期、年龄显着相关。TM4SF19过度表达会导致总生存期(OS)和疾病特异性生存率显着下降。多变量Cox分析将TM4SF19确定为OS的独立危险因素。使用校准图分析了列线图的准确性，显示1年、5年和10年的实际OS值与预测OS值之间具有良好的一致性。结果表明，TM4SF19的上调与疾病的进展和不良预后相关。TM4SF19有望作为BLCA患者诊断和预后的生物标志物。

Abstract: In recent years, scientific research has confirmed that TM4SF19 in the four-transmembrane L6 su-perfamily plays an important role in the occurrence and development of tumors. However, the role of TM4SF19 in the prognosis and immune invasion of bladder urothelial carcinoma (BLCA) remains unclear. This study explores the expression of TM4SF19 in tumor tissues and its relationship with immune invasion and determines its prognostic role in BLCA patients. This study obtained patients’ expression profiles and clinical information from The Cancer Genome Atlas (TCGA) database. Mann- Whitney U test (Wilcoxon rank sum test) analyzed the differential expression of TM4SF19 in BLCA. Functional enrichment analysis was performed to explore the potential signaling pathways and bio-logical functions involved. Immune cell infiltration was assessed using single-sample gene set enrichment analysis. The Kaplan-Meier method and Cox regression analysis were used to determine the prognostic value of TM4SF19. Nomograms were constructed to predict overall survival (OS) rates at 1, 5, and 10 years after cancer diagnosis. Results: TM4SF19 is overexpressed in BLCA. Multiple pathways were significantly enriched in the TM4SF19 high-expression group, including many tumor-related pathways and immune-related pathways. TM4SF19 expression was positively correlated with macrophages, Th1 cells, and other immune cells, but negatively correlated with NKCD56 bright cells and mast cells. The expression level of TM4SF19 was significantly related to the T stage, N stage, and age. Overexpression of TM4SF19 results in a significant decrease in overall sur-vival (OS) and disease-specific survival. Multivariate Cox analysis identified TM4SF19 as an inde-pendent risk factor for OS. The accuracy of the nomogram was analyzed using calibration plots, showing good agreement between actual and predicted OS values at 1, 5, and 10 years. The results showed that upregulation of TM4SF19 was associated with disease progression and poor prognosis. TM4SF19 is expected to serve as a biomarker for the diagnosis and prognosis of BLCA patients.