Liu Zhi, Zhang Jun, Shen Deyun, Hu Xuechun, Ke Zongpan, Ehrich Lister I Nyoman, Sihombing Bungaran
Department of Urology Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Department of Urinary Surgery, The 901st Hospital of the Joint Logistics Support Force of PLA, Hefei, Anhui, China.
Front Genet. 2023 Jan 9;13:873884. doi: 10.3389/fgene.2022.873884. eCollection 2022.
Cytoskeleton-associated protein 2-like protein (CKAP2L) is thought to promote the progression of glioma, breast cancer, and ovarian cancer. However, the role of cytoskeleton-associated protein 2-like protein in clear cell renal cell carcinoma (ccRCC) is still unclear. The study aimed to investigate the roles and mechanisms of cytoskeleton-associated protein 2-like protein in clear cell renal cell carcinoma. The level of cytoskeleton-associated protein 2-like protein in tumors was explored by using UALCAN and Oncomine databases. Gene expression datasets of clear cell renal cell carcinoma from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) were also used to validate the cytoskeleton-associated protein 2-like protein level in clear cell renal cell carcinoma. Survival analysis was performed to investigate the relationship between cytoskeleton-associated protein 2-like protein level and prognosis of clear cell renal cell carcinoma patients. Cox regression analysis was used for identifying the independent prognostic factors. Gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), protein-protein interaction analysis, co-expression analysis, and immune infiltration analysis were used to explore the potential mechanisms of cytoskeleton-associated protein 2-like protein in clear cell renal cell carcinoma. Moreover, the levels of cytoskeleton-associated protein 2-like protein in clinical clear cell renal cell carcinoma tissues were also measured using RT-PCR, immunohistochemical analysis, and Western blotting. M1 macrophages and CD4 T cells were also detected by immunohistochemistry between tumor and normal tissues. The level of cytoskeleton-associated protein 2-like protein was upregulated in clear cell renal cell carcinoma according to multiple databases and experimental verification. Upregulated cytoskeleton-associated protein 2-like protein is an independent prognostic factor, which might activate the JAK-STAT signaling pathway, the P53 signaling pathway, the TGF-β signaling pathway, the WNT signaling pathway, , in clear cell renal cell carcinoma. Protein-protein interaction analysis and co-expression analysis suggest that cytoskeleton-associated protein 2-like protein might interact with some proliferation proteins. Immune infiltration analysis indicates that cytoskeleton-associated protein 2-like protein may affect the level of activated CD4 memory T cells, M1 macrophages, CD8 T cells, and neutrophils in clear cell renal cell carcinoma. More M1 macrophage infiltrations in tumor tissues with higher cytoskeleton-associated protein 2-like protein were validated by clear cell renal cell carcinoma tumor tissues. Cytoskeleton-associated protein 2-like protein is upregulated in clear cell renal cell carcinoma tissues, which may promote progression of the disease. Cytoskeleton-associated protein 2-like protein is a potential target for prognostic markers and a potential treatment target in clear cell renal cell carcinoma.
细胞骨架相关蛋白2样蛋白（CKAP2L）被认为可促进神经胶质瘤、乳腺癌和卵巢癌的进展。然而，细胞骨架相关蛋白2样蛋白在肾透明细胞癌（ccRCC）中的作用仍不清楚。本研究旨在探讨细胞骨架相关蛋白2样蛋白在肾透明细胞癌中的作用及机制。通过使用UALCAN和Oncomine数据库探索肿瘤中细胞骨架相关蛋白2样蛋白的水平。来自癌症基因组图谱和基因表达综合数据库（GEO）的肾透明细胞癌基因表达数据集也用于验证肾透明细胞癌中细胞骨架相关蛋白2样蛋白的水平。进行生存分析以研究细胞骨架相关蛋白2样蛋白水平与肾透明细胞癌患者预后之间的关系。采用Cox回归分析确定独立预后因素。利用基因集富集分析（GSEA）、基因集变异分析（GSVA）、蛋白质-蛋白质相互作用分析、共表达分析和免疫浸润分析来探索细胞骨架相关蛋白2样蛋白在肾透明细胞癌中的潜在机制。此外，还采用逆转录-聚合酶链反应（RT-PCR）、免疫组织化学分析和蛋白质免疫印迹法检测临床肾透明细胞癌组织中细胞骨架相关蛋白2样蛋白的水平。通过免疫组织化学法检测肿瘤组织和正常组织之间的M1巨噬细胞和CD4 T细胞。根据多个数据库和实验验证，肾透明细胞癌中细胞骨架相关蛋白2样蛋白水平上调。上调的细胞骨架相关蛋白2样蛋白是一个独立的预后因素，它可能激活肾透明细胞癌中的JAK-STAT信号通路、P53信号通路、TGF-β信号通路、WNT信号通路等。蛋白质-蛋白质相互作用分析和共表达分析表明，细胞骨架相关蛋白2样蛋白可能与一些增殖蛋白相互作用。免疫浸润分析表明，细胞骨架相关蛋白2样蛋白可能影响肾透明细胞癌中活化的CD4记忆T细胞、M1巨噬细胞、CD8 T细胞和中性粒细胞的水平。肾透明细胞癌肿瘤组织证实，细胞骨架相关蛋白2样蛋白水平较高的肿瘤组织中有更多的M1巨噬细胞浸润。肾透明细胞癌组织中细胞骨架相关蛋白2样蛋白上调，可能促进疾病进展。细胞骨架相关蛋白2样蛋白是肾透明细胞癌预后标志物的潜在靶点和潜在治疗靶点。
