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泛癌症分析人类腺瘤性结肠息肉病的致癌效应。

A pan-cancer analysis on the carcinogenic effect of human adenomatous polyposis coli.

机构信息

Medical School, Anhui University of Science and Technology, Huainan, China.

Institute of Environment-Friendly Materials and Occupational Health of Anhui University of Science and Technology (Wuhu), Wuhu, China.

出版信息

PLoS One. 2022 Mar 18;17(3):e0265655. doi: 10.1371/journal.pone.0265655. eCollection 2022.

DOI:10.1371/journal.pone.0265655
PMID:35303016
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8932560/
Abstract

Adenomatous polyposis coli (APC) is the most commonly mutated gene in colon cancer and can cause familial adenomatous polyposis (FAP). Hypermethylation of the APC promoter can also promote the development of breast cancer, indicating that APC is not limited to association with colorectal neoplasms. However, no pan-cancer analysis has been conducted. We studied the location and structure of APC and the expression and potential role of APC in a variety of tumors by using The Cancer Genome Atlas and Gene Expression Omnibus databases and online bioinformatics analysis tools. The APC is located at 5q22.2, and its protein structure is conserved among H. sapiens, M. musculus with C. elaphus hippelaphus. The APC identity similarity between homo sapiens and mus musculus reaches 90.1%. Moreover, APC is highly specifically expressed in brain tissues and bipolar cells but has low expression in most cancers. APC is mainly expressed on the cell membrane and is not detected in plasma by mass spectrometry. APC is low expressed in most tumor tissues, and there is a significant correlation between the expressed level of APC and the main pathological stages as well as the survival and prognosis of tumor patients. In most tumors, APC gene has mutation and methylation and an enhanced phosphorylation level of some phosphorylation sites, such as T1438 and S2260. The expressed level of APC is also involved in the level of CD8+ T-cell infiltration, Tregs infiltration, and cancer-associated fibroblast infiltration. We conducted a gene correlation study, but the findings seemed to contradict the previous analysis results of the low expression of the APC gene in most cancers. Our research provides a comparative wholesale understanding of the carcinogenic effects of APC in various cancers, which will help anti-cancer research.

摘要

腺瘤性结肠息肉病(APC)是结肠癌中最常突变的基因,可导致家族性腺瘤性息肉病(FAP)。APC 启动子的高甲基化也可促进乳腺癌的发展,表明 APC 不仅与结直肠肿瘤有关。然而,尚未进行泛癌症分析。我们使用癌症基因组图谱和基因表达综合数据库以及在线生物信息学分析工具,研究了 APC 的位置和结构,以及 APC 在多种肿瘤中的表达和潜在作用。APC 位于 5q22.2,其蛋白结构在智人、小家鼠和盘羊中是保守的。智人与小家鼠的 APC 身份相似度达到 90.1%。此外,APC 在脑组织和双极细胞中高度特异性表达,但在大多数癌症中的表达水平较低。APC 主要表达在细胞膜上,通过质谱法在血浆中未检测到。APC 在大多数肿瘤组织中低表达,并且 APC 的表达水平与主要病理阶段以及肿瘤患者的生存和预后之间存在显著相关性。在大多数肿瘤中,APC 基因发生突变和甲基化,某些磷酸化位点(如 T1438 和 S2260)的磷酸化水平增强。APC 的表达水平也与 CD8+T 细胞浸润、Tregs 浸润和癌症相关成纤维细胞浸润的水平有关。我们进行了基因相关性研究,但结果似乎与 APC 基因在大多数癌症中低表达的先前分析结果相矛盾。我们的研究提供了对 APC 在各种癌症中致癌作用的全面比较理解,这将有助于抗癌研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ea1/8932560/809f16ee63fd/pone.0265655.g009.jpg
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