Wang Weiyu, Ma Shengyao, Ding Zhenyu, Yang Yang, Wang Huaijie, Yang Kunning, Cai Xiaoshan, Li Hanyue, Gao Zhiqin, Qu Meihua
Translational Medical Center, Weifang Second People's Hospital, The Second Affiliated Hospital of Weifang Medical University, Weifang, China.
Biopharmaceutical Laboratory, Key Laboratory of Shandong Province Colleges and Universities, School of Life Science and Technology, Weifang Medical University, Weifang, China.
Front Pharmacol. 2021 Nov 3;12:707940. doi: 10.3389/fphar.2021.707940. eCollection 2021.
Xeroderma Pigmentosum Complementation Group C (XPC) is a protein involving in nucleotide excision repair (NER). XPC also plays an important role in the lung cancer occurrence with the mechanism remian unclear up to date. Studies showed that the increased stemness of lung cancer cells is related to the recurrence and metastasis of lung cancer. This study aimed to study and analyze the correlation of XPC with lung cancer stem cell biomarkers expression and the overall survival (OS) of lung adenocarcinoma patients. 140 cases of clinical lung adenocarcinoma tissue samples and 48 cases of paired paracancerous tissue samples were made into tissue microarray. Immunohistochemistry (IHC) was used to detect the expression of XPC and CD133 in cancer and paracancerous tissues. Semi-quantitative analysis and statistics were performed by Pannoramic Digital Slide Scanner. The expression of XPC and CD133 in fresh tissues was verified by Western blotting assay. siXPC was used to knock down XPC in lung cancer cell lines to study the effect of XPC on the expression of lung cancer stem cell biomarkers and the ability of cell invasion. And shXPC was used to knockdown XPC in A549 and H1650 to study the effect of XPC on the expression of lung cancer stem cell biomarkers. IHC and Western blotting results showed that XPC expression significantly decreased, while CD133 expression significantly increased in cancer tissues comparing to paracancerous tissues ( < 0.0001, = 0.0395). The high level of XPC in cancer was associated with a better prognosis ( = 0.0577) in lung adenocarcinoma patients. Downregulation of XPC in lung cancer cells showed increased expression of cancer stem cell biomarkers and the increased cell invasion abilities. It is suggested that XPC can exert the ability of anti-tumor formation, tumor invasion and metastasis inhibition, and prognostic survival improvement in lung adenocarcinoma patients by regulating the stemness of lung cancer cells.
着色性干皮病C互补组（XPC）是一种参与核苷酸切除修复（NER）的蛋白质。XPC在肺癌发生中也起着重要作用，但其机制至今仍不清楚。研究表明，肺癌细胞干性增加与肺癌的复发和转移有关。本研究旨在研究和分析XPC与肺癌干细胞生物标志物表达及肺腺癌患者总生存期（OS）的相关性。将140例临床肺腺癌组织样本和48例配对的癌旁组织样本制成组织芯片。采用免疫组织化学（IHC）法检测癌组织和癌旁组织中XPC和CD133的表达。通过全景数字切片扫描仪进行半定量分析和统计。采用蛋白质免疫印迹法验证新鲜组织中XPC和CD133的表达。使用siXPC敲低肺癌细胞系中的XPC，以研究XPC对肺癌干细胞生物标志物表达和细胞侵袭能力的影响。使用shXPC敲低A549和H1650中的XPC，以研究XPC对肺癌干细胞生物标志物表达的影响。免疫组织化学和蛋白质免疫印迹结果显示，与癌旁组织相比，癌组织中XPC表达显著降低，而CD133表达显著增加（<0.0001，=0.0395）。癌组织中高水平的XPC与肺腺癌患者较好的预后相关（=0.0577）。肺癌细胞中XPC的下调显示癌干细胞生物标志物表达增加，细胞侵袭能力增强。提示XPC可通过调节肺癌细胞的干性发挥抗肿瘤形成、抑制肿瘤侵袭和转移以及改善肺腺癌患者预后生存的能力。
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