锌指蛋白37A（ZNF37A）表达下调促进肿瘤坏死因子受体超家族成员6B（TNFRSF6B）表达，并导致直肠癌患者对同步放化疗产生治疗抵抗。
ZNF37A downregulation promotes TNFRSF6B expression and leads to therapeutic resistance to concurrent chemoradiotherapy in rectal cancer patients.
作者信息
Huang Ying, Jin Jing, Ren Ningxin, Chen Hongxia, Qiao Yan, Zou Shuangmei, Wang Xin, Zheng Linlin, Li Ye-Xiong, Tan Wen, Lin Dongxin
机构信息
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, PR China; Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou 510120, PR China.
Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, PR China; Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, 518100, PR China.
出版信息
Transl Oncol. 2025 Jan;51:102203. doi: 10.1016/j.tranon.2024.102203. Epub 2024 Nov 20.
The identification a signature comprising a group of genes as markers of cancer response to chemoradiotherapy would be more appropriate and effective for predicting chemoradiotherapy efficacy. This study investigated the differentially expressed genes (DEGs) related to chemoradiotherapy resistance and established a multigene expression model for predicting the sensitivity of rectal cancer to chemoradiotherapy in rectal cancer patients, elucidated the mechanism of resistance to synchronized chemoradiotherapy. The genome-wide expression profiling microarray were performed in the tissues of 81 rectal cancer patients before neoadjuvant therapy to analyze and discover DEGs related to chemoradiotherapy resistance, and the results were verified in 45 rectal cancer patients, and finally a 20-gene signature was proposed to be a predictor of chemoradiotherapy response. Molecular biology experiments revealed that zinc finger protein 37A (ZNF37A) downregulation leads to therapeutic resistance. This study identified a 20-gene signature with group of genes can help predict the response to chemoradiotherapy of rectal cancer patients. ZNF37A demonstrated a statistically significant correlation with sensitivity to chemoradiotherapy and survival in patients with LARC who underwent chemoradiotherapy. The findings revealed that ZNF37A bound to the tumor necrosis factor receptor superfamily member 6B (TNFRSF6B) promoter region, thereby suppressing its transcriptional activity. Reduced expression of ZNF37A induces chemoradiation resistance by inhibiting apoptosis in colorectal cancer (CRC) cells. TNFRSF6B Knockdown restored the sensitivity of CRC to chemoradiotherapy. ZNF37A is an effective modulator of chemoradiotherapy response in rectal cancer. These findings elucidate the molecular mechanism underlying chemoradiotherapy resistance and provide potential applications for individualized clinical therapy.
鉴定一组基因组成的特征性标志物以预测癌症对放化疗的反应，对于预测放化疗疗效而言更为合适且有效。本研究调查了与放化疗耐药相关的差异表达基因（DEGs），并建立了一个多基因表达模型，用于预测直肠癌患者对放化疗的敏感性，阐明了同步放化疗耐药的机制。对81例直肠癌患者新辅助治疗前的组织进行全基因组表达谱微阵列分析，以分析并发现与放化疗耐药相关的DEGs，并在45例直肠癌患者中对结果进行验证，最终提出一个由20个基因组成的特征性标志物作为放化疗反应的预测指标。分子生物学实验表明，锌指蛋白37A（ZNF37A）表达下调导致治疗耐药。本研究鉴定出一个由20个基因组成的特征性标志物，有助于预测直肠癌患者对放化疗的反应。ZNF37A与接受放化疗的局部晚期直肠癌（LARC）患者的放化疗敏感性及生存具有统计学显著相关性。研究结果显示，ZNF37A与肿瘤坏死因子受体超家族成员6B（TNFRSF6B）启动子区域结合，从而抑制其转录活性。ZNF37A表达降低通过抑制结直肠癌（CRC）细胞凋亡诱导放化疗耐药。敲低TNFRSF6B可恢复CRC对放化疗的敏感性。ZNF37A是直肠癌放化疗反应的有效调节因子。这些发现阐明了放化疗耐药的分子机制，并为个体化临床治疗提供了潜在应用。
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