Liu Yiqi, Li Haobing, Shen Xiangyu, Liu Ying, Zhong Xiaoxiao, Zhong Jing, Cao Renxian
The First Affiliated Hospital, Hengyang Medical School, University of South China Hengyang 421001, Hunan, China.
Institute of Clinical Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China Hengyang 421200, Hunan, China.
Am J Cancer Res. 2024 Aug 25;14(8):3711-3732. doi: 10.62347/TYLL7952. eCollection 2024.
Protein L-isoaspartyl (D-aspartyl) methyltransferase (PIMT, gene name PCMT1) is an enzyme that repairs proteins with altered aspartate residues by methylation, restoring their normal structure and function. This study conducted a comprehensive analysis of PCMT1 in pan-cancer. The Cancer Genome Atlas, Human Protein Atlas website, and the Genotype-Tissue Expression were utilized in analysis of PCMT1 expression. We examined the association between PCMT1 expression and various factors, including gene modifications, DNA methylation, immune cell infiltration, immunological checkpoints, drug susceptibility, tumor mutation burden (TMB), and microsatellite instability (MSI). Enrichment analyses determined the potential biological roles and pathways involving PCMT1. Our focus then shifted to the role of PCMT1 in breast invasive carcinoma (BRCA). We found that PCMT1 expression was aberrant in many tumors and significantly influenced the prognosis across several cancer types. Gene alterations in PCMT1 predominantly involved deep deletions and amplifications. A negative correlation was observed between DNA methylation and PCMT1 expression across all studied cancer types except thyroid carcinoma PCMT1 exhibited positive correlations with common lymphoid progenitor and CD4(+) T helper 2 cells, whereas it was inversely correlated with central and effector memory T cells, memory CD8(+) T cells, and CD4(+) T helper 1 cells. In many cancer types, PCMT1 expression closely correlated with immunological checkpoint inhibitors, TMB, and MSI. It was also significantly linked to pathways involved in epithelial-mesenchymal transition (EMT), highlighting its role in cancer metastasis. PCMT1 emerged as a significant predictor of breast cancer progression. In vitro experiments demonstrated that reducing PCMT1 expression decreased BRCA cell migration and invasiveness. Additionally, animal studies confirmed that inhibition of PCMT1 slowed tumor growth.
蛋白质L-异天冬氨酰(D-天冬氨酰)甲基转移酶(PIMT,基因名称为PCMT1)是一种通过甲基化修复天冬氨酸残基发生改变的蛋白质的酶,可恢复其正常结构和功能。本研究对泛癌中的PCMT1进行了全面分析。利用癌症基因组图谱、人类蛋白质图谱网站和基因型-组织表达数据库分析PCMT1的表达情况。我们研究了PCMT1表达与各种因素之间的关联,包括基因修饰、DNA甲基化、免疫细胞浸润、免疫检查点、药物敏感性、肿瘤突变负荷(TMB)和微卫星不稳定性(MSI)。富集分析确定了涉及PCMT1的潜在生物学作用和途径。然后我们将重点转向PCMT1在乳腺浸润性癌(BRCA)中的作用。我们发现PCMT1在许多肿瘤中表达异常,并显著影响多种癌症类型的预后。PCMT1的基因改变主要涉及深度缺失和扩增。在所有研究的癌症类型中,除甲状腺癌外,DNA甲基化与PCMT1表达呈负相关;PCMT1与常见淋巴祖细胞和CD4(+)辅助性T细胞2呈正相关,而与中枢记忆T细胞、效应记忆T细胞、记忆性CD8(+)T细胞和CD4(+)辅助性T细胞1呈负相关。在许多癌症类型中,PCMT1表达与免疫检查点抑制剂、TMB和MSI密切相关。它还与上皮-间质转化(EMT)相关途径显著相关,突出了其在癌症转移中的作用。PCMT1成为乳腺癌进展的重要预测指标。体外实验表明,降低PCMT1表达可降低BRCA细胞的迁移和侵袭能力。此外,动物研究证实抑制PCMT1可减缓肿瘤生长。