Jiang Yinfeng, Pan Tingan, Zhang Zhenglin
Department of Urology, Changzhou Medical Center, Changzhou Third People's Hospital, Nanjing Medical University, Nanjing, China.
Discov Oncol. 2025 Jun 17;16(1):1127. doi: 10.1007/s12672-025-02877-6.
Prostate adenocarcinoma (PRAD) is a prevalent urinary tumor with an elusive etiology. While transmembrane protein 100 (TMEM100) plays diverse roles in various cancers, its involvement in prostate cancer remains unexplored. Herein, we aim to elucidate the impact of TMEM100 on prostate cancer diagnosis and progression.
Utilizing data from the TCGA database, we analyzed mRNA sequences, clinical information, and methylation data. Prognostic analysis was conducted using the GEPIA database, and a nomogram was developed using the "rms" package in R software. Drug sensitivity was assessed using the "pRRophetic" package. The correlation between TMEM100 and immune infiltration was investigated using the TIMER and TISDIB databases. Methylation levels were evaluated using Perl and R software. The competitive endogenous RNA (ceRNA) network was constructed using the starBase database. Functional assays including qRT-PCR, CCK8, EdU, and IHC assays were employed to evaluate TMEM100's role in PRAD.
TMEM100 expression was significantly reduced in prostate cancer tissues compared to normal tissues, correlating with poor prognosis in PRAD. The multivariable model nomogram demonstrated enhanced prediction of PFI. Additionally, the low-expression TMEM100 group exhibited lower IC50 values for several chemotherapy drugs. TMEM100 was closely associated with various immune cell types, immunomodulators, and chemokines, exerting anti-tumor effects. Higher methylation levels of TMEM100 were observed in PRAD, with specific CpG sites showing significant correlation. TMEM100 hypermethylation correlated with immune infiltration in PCa. Furthermore, a TMEM100-related ceRNA network was constructed in PRAD, corroborating TMEM100's role in PCa through functional experiments.
TMEM100 downregulation, through modulation of immune infiltration and epigenetic mechanisms, correlates with poor prognosis and tumor cell proliferation in PRAD.
前列腺腺癌（PRAD）是一种常见的泌尿系统肿瘤，其病因尚不明确。虽然跨膜蛋白100（TMEM100）在多种癌症中发挥着不同作用，但其在前列腺癌中的作用仍未得到探索。在此，我们旨在阐明TMEM100对前列腺癌诊断和进展的影响。
利用来自TCGA数据库的数据，我们分析了mRNA序列、临床信息和甲基化数据。使用GEPIA数据库进行预后分析，并使用R软件中的“rms”包开发列线图。使用“pRRophetic”包评估药物敏感性。使用TIMER和TISDIB数据库研究TMEM100与免疫浸润之间的相关性。使用Perl和R软件评估甲基化水平。使用starBase数据库构建竞争性内源性RNA（ceRNA）网络。采用包括qRT-PCR、CCK8、EdU和免疫组化分析在内的功能实验来评估TMEM100在PRAD中的作用。
与正常组织相比，前列腺癌组织中TMEM100表达显著降低，这与PRAD的不良预后相关。多变量模型列线图显示对无进展生存期（PFI）的预测能力增强。此外，低表达TMEM100组对几种化疗药物的IC50值较低。TMEM100与多种免疫细胞类型、免疫调节剂和趋化因子密切相关，发挥抗肿瘤作用。在PRAD中观察到TMEM100的甲基化水平较高，特定的CpG位点显示出显著相关性。TMEM100高甲基化与前列腺癌中的免疫浸润相关。此外，在PRAD中构建了一个与TMEM100相关的ceRNA网络，通过功能实验证实了TMEM100在前列腺癌中的作用。
TMEM100的下调通过调节免疫浸润和表观遗传机制，与PRAD的不良预后和肿瘤细胞增殖相关。
