Xu Chuan, Liu Mingshan, Li Yang, Peng Xiaoyue, Zhou Wei, Zhang Wan, Zhang Jingtao, Yu Bentong
Department of Thoracic Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China.
Jiangxi Hospital of China-Japan Friendship Hospital, National Regional Center for Respiratory Medicine Nanchang, Jiangxi, 330000, People's Republic of China.
Discov Oncol. 2025 Mar 6;16(1):270. doi: 10.1007/s12672-025-01986-6.
Chromatin modified protein 4C (CHMP4C) is a charged polyvesicular protein (CHMP) that is involved in the composition of the endosomal sorting complex (ESCRT-III) required for transport III and promotes the necessary separation of daughter cells. CHMP4C involved in a wide variety of tumor progress, such as prostate cancer, cervical cancer and lung squamous cell carcinoma. However, the value of CHMP4C in lung adenocarcinoma has not been explored.
RNA-seq data and lung adenocarcinoma clinical information and corresponding pan-cancer were extracted from The Cancer Genome Atlas (TCGA) database to analyze CHMP4C expression and survival prognosis. The differential expression of CHMP4C was analyzed using the Human Protein Atlas (HPA) database. Clinical samples were collected to verify the differential expression of CHMP4C between lung adenocarcinoma and normal lung tissues via immunohistochemical (IHC) staining, qRT‒PCR and Western blotting. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of CHMP4C-related genes were performed. The correlation between CHMP4C and chemosensitivity was analyzed in the TCGA database. Then, qRT‒PCR, western blotting, transwell assays, cell proliferation assays, colony formation assays, wound healing assays, and cell cycle analysis were used to verify the possible regulatory mechanism involved. Molecular docking was used to predict small molecule compounds with potential roles in the treatment of lung adenocarcinoma.
TIMER2.0 database analysis revealed that CHMP4C was differentially expressed in different tumors.Compared with that in healthy lung tissue, CHMP4C was significantly upregulated in lung adenocarcinoma tissue, and subsequent in vitro survival analysis revealed that CHMP4C expression has significant clinical prognostic value in lung adenocarcinoma. Enrichment analysis revealed that CHMP4C was mainly related to cell proliferation, cell migration, and the PI3K-Akt signaling pathway, etc. Overexpression of CHMP4C was associated with sensitivity to chemotherapy. Knocking down CHMP4C can significantly inhibit the proliferation, migration and invasion of lung adenocarcinoma cells and prolong the G0/G1 phase of the cell cycle. Molecular docking predicts 10 key drugs that may be used for the treatment of lung adenocarcinoma.
CHMP4C is highly expressed in a variety of tumors. We demonstrated that CHMP4C expression may be associated with the occurrence, development, prognosis and chemotherapy sensitivity in patients with lung adenocarcinoma. These findings may open up new research directions and development opportunities for the treatment of lung adenocarcinoma.
染色质修饰蛋白4C（CHMP4C）是一种带电荷的多囊泡蛋白（CHMP），参与运输III所需的内体分选复合物（ESCRT-III）的组成，并促进子细胞的必要分离。CHMP4C参与多种肿瘤进展，如前列腺癌、宫颈癌和肺鳞状细胞癌。然而，CHMP4C在肺腺癌中的价值尚未得到探索。
从癌症基因组图谱（TCGA）数据库中提取RNA测序数据、肺腺癌临床信息及相应的泛癌数据，以分析CHMP4C的表达及生存预后。使用人类蛋白质图谱（HPA）数据库分析CHMP4C的差异表达。收集临床样本，通过免疫组织化学（IHC）染色、qRT-PCR和蛋白质印迹法验证肺腺癌与正常肺组织中CHMP4C的差异表达。对CHMP4C相关基因进行基因本体（GO）、京都基因与基因组百科全书（KEGG）富集分析。在TCGA数据库中分析CHMP4C与化疗敏感性之间的相关性。然后，使用qRT-PCR、蛋白质印迹法、Transwell实验、细胞增殖实验、集落形成实验、伤口愈合实验和细胞周期分析来验证可能涉及的调控机制。使用分子对接预测在肺腺癌治疗中具有潜在作用的小分子化合物。
TIMER2.0数据库分析显示，CHMP4C在不同肿瘤中存在差异表达。与健康肺组织相比，CHMP4C在肺腺癌组织中显著上调，随后的体外生存分析显示，CHMP4C表达在肺腺癌中具有显著的临床预后价值。富集分析显示，CHMP4C主要与细胞增殖、细胞迁移和PI3K-Akt信号通路等相关。CHMP4C的过表达与化疗敏感性相关。敲低CHMP4C可显著抑制肺腺癌细胞的增殖、迁移和侵袭，并延长细胞周期的G0/G1期。分子对接预测了10种可能用于治疗肺腺癌的关键药物。
CHMP4C在多种肿瘤中高表达。我们证明CHMP4C表达可能与肺腺癌患者的发生、发展、预后及化疗敏感性相关。这些发现可能为肺腺癌的治疗开辟新的研究方向和发展机会。
