Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, P.R. China.
Int J Oncol. 2022 Jun;60(6). doi: 10.3892/ijo.2022.5356. Epub 2022 Apr 15.
Studies have shown that PCNA clamp associated factor (PCLAF) plays a paramount role in a variety of cancers; however, the expression profile and the specific molecular mechanism of PCLAF in cancer remains unclear, as is its value in the human pan‑cancer analysis. Based on the publicly available datasets of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), a comprehensive analysis of the probable carcinogenic effects of the gene was performed in 33 human cancers. It was found that is highly expressed in cancer tissues compared with normal tissues, and is significantly correlated with poor prognosis. We found that the eight tumors with significantly high PCLAF expression presented with decreased DNA methylation levels of PCLAF, including cholangiocarcinoma (CHOL), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), glioblastoma multiforme (GBM), pheochromocytoma and paraganglioma (PCPG), sarcoma (SARC), testicular germ cell tumor (TGCT), stomach adenocarcinoma (STAD), and uterine corpus endometrial carcinoma (UCEC). The expression of PCLAF was found to be positively correlated with activated CD4 T cells (Act CD4) and type 2 T helper (Th2) cells, suggesting that PCLAF may play a particular role in tumor immune infiltration. In addition, the functional mechanism of PCLAF also involves the mitotic cell cycle process, cell division, and DNA replication. Our first pan‑cancer study provides a relatively extensive understanding of the carcinogenic effects of PCLAF in miscellaneous tumors.
研究表明,增殖细胞核抗原连接因子(PCNA clamp associated factor,PCLAF)在多种癌症中发挥着至关重要的作用;然而,PCLAF 在癌症中的表达谱和具体分子机制尚不清楚,其在人类泛癌分析中的价值也尚未可知。本研究基于癌症基因组图谱(The Cancer Genome Atlas,TCGA)和基因表达综合数据库(Gene Expression Omnibus,GEO)中公开的数据集,对 33 种人类癌症中该基因的潜在致癌作用进行了综合分析。结果发现,与正常组织相比, 在癌症组织中高表达,且与预后不良显著相关。我们发现,8 种表达水平显著升高的肿瘤组织中 PCLAF 的 DNA 甲基化水平降低,这些肿瘤包括胆管癌(cholangiocarcinoma,CHOL)、宫颈鳞状细胞癌和子宫颈内膜腺癌(cervical squamous cell carcinoma and endocervical adenocarcinoma,CESC)、胶质母细胞瘤(glioblastoma multiforme,GBM)、嗜铬细胞瘤和副神经节瘤(pheochromocytoma and paraganglioma,PCPG)、肉瘤(sarcoma,SARC)、睾丸生殖细胞肿瘤(testicular germ cell tumor,TGCT)、胃腺癌(stomach adenocarcinoma,STAD)和子宫内膜癌(uterine corpus endometrial carcinoma,UCEC)。PCLAF 的表达与激活的 CD4 T 细胞(activated CD4 T cells,Act CD4)和 2 型 T 辅助细胞(type 2 T helper cells,Th2)呈正相关,提示 PCLAF 可能在肿瘤免疫浸润中发挥特殊作用。此外,PCLAF 的功能机制还涉及有丝分裂细胞周期过程、细胞分裂和 DNA 复制。本项首次泛癌研究为 PCLAF 在多种肿瘤中的致癌作用提供了较为广泛的认识。