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含寿司结构域蛋白4(SUSD4)的泛癌分析及其在结直肠癌中的验证

Pan-cancer analysis of Sushi domain-containing protein 4 (SUSD4) and validated in colorectal cancer.

作者信息

Zhong Yuchen, Zheng Chaojing, Zhang Weiyuan, Wu Hongyu, Zhang Qian, Li Dechuan, Ju Haixing, Feng Haiyang, Chen Yinbo, Fan Yongtian, Chen Weiping, Wang Meng, Wang Guiyu

机构信息

Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, Zhejiang, China.

Department of Colorectal Cancer Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150000, Heilongjiang, China.

出版信息

Aging (Albany NY). 2024 Apr 4;16(7):6417-6444. doi: 10.18632/aging.205712.

Abstract

Sushi domain-containing protein 4 (SUSD4) is a complement regulatory protein whose primary function is to inhibit the complement system, and it is involved in immune regulation. The role of SUSD4 in cancer progression has largely remained elusive. SUSD4 was studied across a variety of cancer types in this study. According to the results, there is an association between the expression level of SUSD4 and prognosis in multiple types of cancer. Further analysis demonstrated that SUSD4 expression level was related to immune cell infiltration, immune-related genes, tumor heterogeneity, and multiple cancer pathways. Additionally, we validated the function of SUSD4 in colorectal cancer cell lines and found that knockdown of SUSD4 inhibited cell growth and impacted the JAK/STAT pathway. By characterizing drug sensitivity in organoids, we found that the expression of SUSD4 showed a positive correlation trend with IC50 of Selumetinib, YK-4-279, and Piperlongumine. In conclusion, SUSD4 is a valuable prognostic indicator for diverse types of cancer, and it has the potential to be a target for cancer therapy.

摘要

含寿司结构域蛋白4(SUSD4)是一种补体调节蛋白,其主要功能是抑制补体系统,并参与免疫调节。SUSD4在癌症进展中的作用在很大程度上仍不明确。本研究对多种癌症类型中的SUSD4进行了研究。结果显示,SUSD4的表达水平与多种癌症类型的预后之间存在关联。进一步分析表明,SUSD4表达水平与免疫细胞浸润、免疫相关基因、肿瘤异质性以及多种癌症通路有关。此外,我们在结肠癌细胞系中验证了SUSD4的功能,发现敲低SUSD4可抑制细胞生长并影响JAK/STAT通路。通过对类器官中的药物敏感性进行表征,我们发现SUSD4的表达与司美替尼、YK-4-279和胡椒碱的半数抑制浓度(IC50)呈正相关趋势。总之,SUSD4是多种癌症类型中一个有价值的预后指标,并且有潜力成为癌症治疗的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b69f/11042942/d9de9e787203/aging-16-205712-g001.jpg

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