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

• Published in: Frontiers in oncology Vol. 13; p. 1170397
• Main Authors: Zhang, Hongtuan, Liu, Dongze, Qin, Zheng, Yi, Bocun, Zhu, Liang, Xu, Shengxian, Wang, Kaibin, Yang, Shaobo, Liu, Ranlu, Yang, Kuo, Xu, Yong
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 14.06.2023
• Subjects: accurate treatment; anti-tumor; CHMP4C; diagnostic and prognostic biomarkers; Oncology; prostate cancer; CHMP4C; anti-tumor; prostate cancer; accurate treatment; diagnostic and prognostic biomarkers
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2023.1170397

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.