Li Hongxia, Yang Qiwei, Huo Sibo, Du Zhenwu, Wu Fei, Zhao Haiyue, Chen Shifan, Yang Longfei, Ma Zhiming, Sui Yujie
Department of Dermatology, First Hospital of Jilin University, Changchun, China.
Key Laboratory for Molecular and Chemical Genetics of Critical Human Diseases of Jilin Province, Second Hospital of Jilin University, Changchun, China.
Front Oncol. 2021 Mar 19;11:652262. doi: 10.3389/fonc.2021.652262. eCollection 2021.
TMEM16A is a recently identified calcium-activated chloride channel (CaCC) and its overexpression contributes to tumorigenesis and progression in several human malignancies. However, little is known about expression of TMEM16A and its clinical significance in colorectal cancer (CRC). TMEM16A mRNA expression was determined by quantitative real time-PCR (qRT-PCR) in 67 CRC tissues and 24 para-carcinoma tissues. TMEM16A protein expression was performed by immunohistochemistry in 80 CRC tissues. The correlation between TMEM16A expression and clinicopathological parameters, and known genes and proteins involved in CRC was analyzed. The results showed that TMEM16A mRNA expression was frequently detected in 51 CRC tissues (76%), whereas TMEM16A protein expression was determined at a relatively lower frequency (26%). TMEM16A mRNA expression in tumor tissues was higher than its expression in normal para-carcinoma tissues ( < 0.05). TMEM16A mRNA expression was significantly correlated with TNM stage ( = 0.039) and status of lymph node metastasis ( = 0.047). In addition, there was a strong positive correlation between TMEM16A mRNA expression and MSH2 protein. More importantly, TMEM16A protein expression was positively associated with KRAS mutation, and negatively correlated with mutant p53 protein. Logistic regression analysis demonstrated that TMEM16A mRNA expression was an important independent predictive factor of lymph node metastasis (OR = 16.38, CI: 1.91-140.27, = 0.01). TMEM16A mRNA and protein expression was not significantly related with patient survival. Our findings provide original evidence demonstrating TMEM16A mRNA expression can be a novel predictive marker of lymph node metastasis and TMEM16A protein expression may be an important regulator of tumor proliferation and metastasis in CRC.
跨膜蛋白16A（TMEM16A）是一种最近鉴定出的钙激活氯离子通道（CaCC），其过表达促进了多种人类恶性肿瘤的发生和进展。然而，关于TMEM16A在结直肠癌（CRC）中的表达及其临床意义知之甚少。采用定量实时聚合酶链反应（qRT-PCR）检测67例CRC组织和24例癌旁组织中TMEM16A mRNA的表达。采用免疫组织化学法检测80例CRC组织中TMEM16A蛋白的表达。分析TMEM16A表达与临床病理参数以及CRC中已知基因和蛋白之间的相关性。结果显示，51例CRC组织（76%）中频繁检测到TMEM16A mRNA表达，而TMEM16A蛋白表达的检测频率相对较低（26%）。肿瘤组织中TMEM16A mRNA表达高于正常癌旁组织（<0.05）。TMEM16A mRNA表达与TNM分期（=0.039）和淋巴结转移状态（=0.047）显著相关。此外，TMEM16A mRNA表达与错配修复蛋白2（MSH2）呈强正相关。更重要的是，TMEM16A蛋白表达与KRAS突变呈正相关，与突变型p53蛋白呈负相关。逻辑回归分析表明，TMEM16A mRNA表达是淋巴结转移的重要独立预测因素（比值比=16.38，可信区间：1.91-140.27，=0.01）。TMEM16A mRNA和蛋白表达与患者生存率无显著相关性。我们的研究结果提供了原始证据，证明TMEM16A mRNA表达可能是淋巴结转移的一种新型预测标志物，而TMEM16A蛋白表达可能在CRC肿瘤增殖和转移中起重要调节作用。
