CHMP4C as a novel marker regulates prostate cancer progression through cycle pathways and contributes to immunotherapy.

CHMP4C as a novel marker regulates prostate cancer progression through cycle pathways and contributes to immunotherapy.
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DOI:
10.3389/fonc.2023.1170397
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发表时间:
2023
影响因子:
4.7
通讯作者:
Xu, Yong
Xu, Yong
中科院分区:
医学3区
文献类型:
--
作者:
Zhang, Hongtuan;Liu, Dongze;Qin, Zheng;Yi, Bocun;Zhu, Liang;Xu, Shengxian;Wang, Kaibin;Yang, Shaobo;Liu, Ranlu;Yang, Kuo;Xu, Yong

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CHMP4C是一种带电的多囊泡蛋白(CHMP),参与组成转运III所需的内体分选复合体(ESCRT-III),促进子代细胞的必要分离。CHMP4C被认为与不同癌症的进展有关。然而,CHMP4C在前列腺癌中的价值尚未被探索。前列腺癌是男性中最常见的恶性肿瘤,仍然是癌症死亡的主要原因。到目前为止,前列腺癌的临床治疗更倾向于分子分类和特异性的临床治疗和研究。本研究探讨CHMP4C在前列腺癌中的表达及临床预后,并探讨其可能的调控机制。并对CHMP4C在前列腺癌中的免疫状态及相关免疫治疗进行了分析。基于CHMP4C的表达,建立了前列腺癌的一个新亚型,用于精确治疗。我们使用在线数据库Timer、GEPIA2、UALCAN和多个R包研究CHMP4C的表达和相关的临床结果。同时,在不同R包的R软件平台上,进一步探讨CHMP4C在前列腺癌中的生物学功能、免疫微环境和免疫治疗价值。采用定量逆转录聚合酶链式反应、Western blotting、Transwell、CCK8、伤口愈合实验、克隆形成实验和免疫组织化学等方法,验证CHMP4C在前列腺癌中的表达,探讨CHMP4C在前列腺癌发生发展中的作用机制。我们发现CHMP4C在前列腺癌中有明显的表达,CHMP4C的高表达代表前列腺癌的临床预后差和恶性进展。在随后的体外验证中,CHMP4C通过调节细胞周期促进了前列腺癌细胞系的恶性生物学行为。基于CHMP4C的表达,我们建立了两个新的前列腺癌亚型,发现CHMP4C低表达具有更好的免疫应答,而CHMP4C高表达对紫杉醇和5-氟尿嘧啶更敏感。上述发现为前列腺癌的诊断提供了新的标记物,为前列腺癌的精确治疗提供了新的思路。
CHMP4C is one of the charged multivesicular protein (CHMP), and is involved in the composition of the endosomal sorting complex required for transport III (ESCRT-III), facilitating the necessary separation of daughter cells. CHMP4C has been proposed to be involved in the progression of different carcinomas. However, the value of CHMP4C in prostate cancer has not yet been explored. Prostate cancer is the most frequently occurring malignancy among male and remains a leading cause of deaths in cancers. So far, clinical therapy of prostate cancer is more inclined to molecular classification and specific clinical treatment and research. Our study investigated the expression and clinical prognosis of CHMP4C and explored its potential regulatory mechanism in prostate cancer. The immune status of CHMP4C in prostate cancer and relative immunotherapy were then analyzed in our study. Based on CHMP4C expression, a new subtype of prostate cancer was established for precision treatment. We studied the expression of CHMP4C and relative clinical outcome using the online databases TIMER, GEPIA2, UALCAN, and multiple R packages. Meanwhile, the biological function, immune microenvironment and immunotherapy value of CHMP4C in prostate cancer were further explored on the R software platform with different R packages. Then we performed qRT-PCR, Western Blotting, transwell, CCK8, wound healing assay, colony formation assay and immunohistochemistry to verify the expression of CHMP4C, carcinogenesis and potential regulatory mechanisms in prostate cancer. We found that the expression of CHMP4C is significant in prostate cancer and the high expression of CHMP4C represents a poor clinical prognosis and malignant progression of prostate cancer. In subsequent vitro validation, CHMP4C promoted the malignant biological behavior of prostate cancer cell lines by adjusting the cell cycle. Based on CHMP4C expression, we established two new subtypes of prostate cancer and found that low CHMP4C expression has a better immune response while high CHMP4C expression was more sensitive to paclitaxel and 5-fluorouracil. Above findings revealed a new diagnostic marker for prostate cancer and facilitated the subsequent precise treatment of prostate cancer.
DOI: 10.1038/srep42961
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