TRIM69: 结直肠腺癌转移的标志物及对5-氟尿嘧啶和PD-1阻断剂的潜在增敏剂。
TRIM69: a marker of metastasis and potential sensitizer to 5-Fluorouracil and PD-1 blockers in colon adenocarcinoma.
发表日期:2023 Aug 31
作者:
Xiao-Jv Chi, Yi-Bei Song, Deng-He Liu, Li-Qiang Wei, An-Ran Zhao, Xin An, Zi-Zhen Feng, Xiao-Hua Lan, Yu-Meng Lv, Hong-Jun Li, Dong Lan, Hui-Min He
来源:
Cell Death & Disease
摘要:
在三元模体(TRIM)家族中,有几种蛋白与结直肠癌(CRC)的发展相关,但对TRIM69的研究缺乏。本研究旨在考察TRIM69表达与结肠腺癌(COAD)之间的相关性。从癌症基因组图谱中提取COAD患者的mRNA测序数据,分析TRIM69表达与患者临床特征及生存之间的相关性。利用TIMER、Limma、clusterProfiler、GeneMANIA和Gene Set Cancer Analysis平台的多种算法预测与免疫细胞和化疗敏感性的关联。随后,采用聚合酶链反应分析和免疫组化染色检测来实际检测COAD组织样本中的TRIM69表达。TRIM69在COAD组织中的表达低于正常组织,并与病理分期和转移(M类别)相关。此外,TRIM69被发现参与了几个免疫相关途径,特别是NOD样信号通路。这些结果表明,高TRIM69表达有潜力增强肿瘤对5-氟尿嘧啶和程序性细胞死亡蛋白1(PD-1)阻断剂的敏感性。根据我们发现的TRIM69表达在COAD中显著降低,并与病理分期和转移相关,我们得出结论,增加TRIM69表达和/或活性可能有助于改善治疗结果。因此,TRIM69是COAD转移的一个潜在有价值的标志物,也是辅助治疗的一个靶点。© 2023 BioMed Central有限公司,Springer Nature的一部分。
Several proteins in the tripartite-motif (TRIM) family are associated with the development of colorectal cancer (CRC), but research on the role of TRIM69 was lacking. The present study examined the correlation between TRIM69 expression and colon adenocarcinoma (COAD).mRNA sequencing data for COAD patients was extracted from The Cancer Genome Atlas to analyze correlations between TRIM69 expression and patients' clinical features as well as survival. Potential associations with immune cells and chemosensitivity also were predicted using various algorithms in the TIMER, Limma, clusterProfiler, GeneMANIA, and Gene Set Cancer Analysis platforms. Subsequently, polymerase chain reaction analysis and immunohistochemical staining were used to detect TRIM69 expression in COAD tissue samples from real-world patients.TRIM69 expression was lower in COAD tissues than in normal tissues and correlated with the pathologic stage and metastasis (M category). Additionally, TRIM69 was found to be involved in several immune-related pathways, notably the NOD-like signaling pathway. These results suggest that high TRIM69 expression has the potential to enhance tumor sensitivity to 5-fluorouracil and programmed cell death protein 1 (PD-1) blockers.From our findings that TRIM69 expression was significantly reduced in COAD compared with non-cancer tissues and associated with pathologic stage and metastasis, we conclude that increasing TRIM69 expression and/or activity may help to improve therapeutic outcomes. Accordingly, TRIM69 represents a potentially valuable marker of metastasis and target for adjuvant therapy in COAD.© 2023. BioMed Central Ltd., part of Springer Nature.