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TRIM69:结直肠腺癌转移的标志物和 5-氟尿嘧啶及 PD-1 阻滞剂的潜在增敏剂。

TRIM69: a marker of metastasis and potential sensitizer to 5-Fluorouracil and PD-1 blockers in colon adenocarcinoma.

机构信息

Department of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Key Laboratory of Clinical Laboratory Medicine of Guangxi Department of Education, Guangxi Zhuang Autonomous Region, 6 Shuangyong Road, Nanning, 530021, China.

Guangxi Medical University, Guangxi Zhuang Autonomous Region, 22 Shuangyong Road, Nanning, 530021, China.

出版信息

BMC Gastroenterol. 2023 Aug 31;23(1):292. doi: 10.1186/s12876-023-02927-9.

DOI:10.1186/s12876-023-02927-9
PMID:37653392
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10470154/
Abstract

BACKGROUND

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).

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

三基序(TRIM)家族中的几种蛋白质与结直肠癌(CRC)的发生有关,但 TRIM69 的作用研究较少。本研究探讨了 TRIM69 表达与结肠腺癌(COAD)之间的相关性。

方法

从癌症基因组图谱(TCGA)中提取 COAD 患者的 mRNA 测序数据,以分析 TRIM69 表达与患者临床特征和生存之间的相关性。还使用 TIMER、Limma、clusterProfiler、GeneMANIA 和基因集癌症分析平台中的各种算法预测与免疫细胞和化疗敏感性的潜在关联。随后,使用聚合酶链反应分析和免疫组织化学染色检测来自真实世界患者的 COAD 组织样本中的 TRIM69 表达。

结果

COAD 组织中 TRIM69 的表达低于正常组织,与病理分期和转移(M 类别)相关。此外,发现 TRIM69 参与了几种免疫相关途径,特别是 NOD 样信号通路。这些结果表明,高 TRIM69 表达有可能增强肿瘤对 5-氟尿嘧啶和程序性细胞死亡蛋白 1(PD-1)阻滞剂的敏感性。

结论

从我们的研究结果中可以看出,与非癌组织相比,COAD 中 TRIM69 的表达明显降低,并且与病理分期和转移相关,我们得出结论,增加 TRIM69 的表达和/或活性可能有助于改善治疗结果。因此,TRIM69 代表 COAD 中转移的潜在有价值的标志物和辅助治疗的靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3c3/10470154/cdfb5fed6195/12876_2023_2927_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3c3/10470154/621965114df4/12876_2023_2927_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3c3/10470154/e49a9cf83833/12876_2023_2927_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3c3/10470154/9b21da04e92b/12876_2023_2927_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3c3/10470154/b7347ef9071f/12876_2023_2927_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3c3/10470154/ff8ea9996620/12876_2023_2927_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3c3/10470154/cdfb5fed6195/12876_2023_2927_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3c3/10470154/621965114df4/12876_2023_2927_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3c3/10470154/e49a9cf83833/12876_2023_2927_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3c3/10470154/9b21da04e92b/12876_2023_2927_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3c3/10470154/b7347ef9071f/12876_2023_2927_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3c3/10470154/ff8ea9996620/12876_2023_2927_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3c3/10470154/cdfb5fed6195/12876_2023_2927_Fig6_HTML.jpg

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