目的: 探究跨膜蛋白206(TMEM206)在甲状腺癌(TC)中的表达及预后价值。方法: 采用标准化平均差结合随机效应模型分析多中心样本TC与非癌甲状腺组织中TMEM206的表达差异,并运用卡普兰-迈耶法评估其预后价值。结果: TMEM206 mRNA在TC组织相较于非癌甲状腺组织表达升高(SMD=0.42, 95%CI:0.08-0.77),Egger和Begg检验未发现明显偏倚(P＞0.05),通过受试者工作特征曲线评估TMEM206 mRNA的表达特征,其灵敏度为0.57(95%CI:0.39-0.74),特异度为0.84(95%CI:0.58-0.95)。阳性似然比为3.57(95%CI:1.36-9.38),阴性似然比为0.51(95%CI:0.36-0.72)。在蛋白水平上,TC组织的TMEM206表达量较非癌组织显著增加(P＜0.05)。TMEM206是TC患者的危险因素无统计学意义(P＞0.05)。结论: TMEM206在TC中呈现显著高表达,提示其可能参与TC的病理进程,未来需通过功能实验明确其分子机制。
Objective: To investigate the expression and prognostic value of transmembrane protein 206 (TMEM206) in thyroid cancer (TC). Methods: Standardized mean difference combined with random effect model was used to analyze the difference of TMEM206 expression between TC and non-cancerous thyroid tissues in multi-center samples, and Kaplan-Meier method was used to evaluate its prognostic value. Results: The expression of TMEM206 mrna in TC tissues was higher than that in non-cancerous thyroid tissues (SMD=0.42, 95%CI: 0.08-0.77), and Egger and Begg tests showed no significant bias (P＞0.05). The expression characteristics of TMEM206 mrna were evaluated by receiver operating characteristic curve, with a sensitivity of 0.57 (95%CI: 0.39-0.74) and a specificity of 0.84 (95%CI: 0.58-0.95), the positive likelihood ratio was 3.57 (95%CI: 1.36-9.38), and the negative likelihood ratio was 0.51 (95%CI: 0.36-0.72). At the protein level, the expression of TMEM206 in TC tissues was significantly higher than that in non-cancerous tissues (P＜0.05). Conclusion: TMEM206 is highly expressed in TC, suggesting that it may be involved in the pathological process of TC, and its molecular mechanism needs to be clarified through functional experiments in the future.
[1] Bhattacharya S, Mahato RK, Singh S, et al. Advances and challenges in thyroid cancer: The interplay of genetic modulators, targeted therapies, and AI-driven approaches[J]. Life Sci, 2023, 1(332):122110.
[2] Boucai L, Zafereo M, Cabanillas ME. Thyroid Cancer: A Review[J]. Jama, 2024, 331(5): 425-435.
[3] Chen DW, Lang BHH, Mcleod DSA, et al. Thyroid cancer[J]. Lancet, 2023, 401(10387): 1531-1544.
[4] Richmond BK, Gallimore J. Genetic Considerations in the Tumorigenesis, Diagnosis, and Treatment of Differentiated Thyroid Cancer: Current State of the Science[J]. Am Surg, 2023, 89(11): 4853-4859.
[5] Mihaljeviĉ L, Ruan Z, Osei-Owusu J, et al. Inhibition of the proton-activated chloride channel PAC by PIP2[J]. Elife, 2023, 12: e83935.
[6] Deng Z, Zhao Y, Feng J, et al. Cryo-EM structure of a proton-activated chloride channel TMEM206[J]. Sci Adv, 2021, 7(9): eabe5983.
[7] Kostritskaia Y, Klüssendorf M, Pan YE, et al. Physiological Functions of the Volume-Regulated Anion Channel VRAC/LRRC8 and the Proton-Activated Chloride Channel ASOR/TMEM206[J]. Handb Exp Pharmacol, 2024, 283:181-218.
[8] Osei-Owusu J, Yang J, Del Carmen Vitery M, et al. PAC proton-activated chloride channel contributes to acid-induced cell death in primary rat cortical neurons[J]. Channels (Austin), 2020, 14(1): 53-58.
[9] Zhang L, Liu SY, Yang X, et al. TMEM206 is a potential prognostic marker of hepatocellular carcinoma[J]. Oncol Lett, 2020, 20(5): 174.
[10] Peng F, Li H, Li J, et al. Downregulation of the proton-activated Cl-channel TMEM206 inhibits malignant properties of human osteosarcoma cells[J]. Oxid Med Cell Longev, 2021, 2021(1): 3672112.
[11] Zhang W, Li GS, Gan XY, et al. MMP12 serves as an immune cell-related marker of disease status and prognosis in lung squamous cell carcinoma[J]. Peer J, 2023, 11: e15598.
[12] Li SH, Zhai GQ, He RQ, et al. Down-regulation and clinical significance of Sorbin and SH3 domain-containing protein 1 in bladder cancer tissues[J]. IET Syst Biol, 2023, 17(2): 70-82.
[13] Liu Z, Gu S, Lu T, et al. IFI6 depletion inhibits esophageal squamous cell carcinoma progression through reactive oxygen species accumulation via mitochondrial dysfunction and endoplasmic reticulum stress[J]. J Exp Clin Cancer Res, 2020, 39(1): 144.
[14] Kannan S. Molecular Markers in the Diagnosis of Thyroid Cancer in Indeterminate Thyroid Nodules[J]. Indian J Surg Oncol, 2022, 13(1): 11-16.
[15] Yang J, Chen J, Del Carmen Vitery M, et al. PAC, an evolutionarily conserved membrane protein, is a proton-activated chloride channel[J]. Science, 2019, 364(6438): 395-399.
[16] Wang ZH, Peng WB, Zhang P, et al. Lactate in the tumour microenvironment: From immune modulation to therapy[J]. EBioMedicine, 2021, 73: 103627.
[17] Zhang L, Liu SY, Yang X, et al. TMEM206 is a potential prognostic marker of hepatocellular carcinoma[J]. Oncol Lett, 2020, 20(5): 174.
[18] Griffiths JR. Are cancer cells acidic[J]. Br J Cancer, 1991, 64(3): 425-427.
[19] Peng F, Li H, Li J, et al. Downregulation of the Proton-Activated Cl- Channel TMEM206 Inhibits Malignant Properties of Human Osteosarcoma Cells[J]. Oxid Med Cell Longev, 2021, 2021: 3672112.
[20] Pissas KP, Gründer S, Tian Y. Functional expression of the proton sensors ASIC1a, TMEM206, and OGR1 together with BK(Ca) channels is associated with cell volume changes and cell death under strongly acidic conditions in DAOY medulloblastoma cells[J]. Pflugers Arch, 2024, 476(6): 923-937.
[21] Zhao J, Zhu D, Zhang X, et al. TMEM206 promotes the malignancy of colorectal cancer cells by interacting with AKT and extracellular signal-regulated kinase signaling pathways[J]. J Cell Physiol, 2019, 234(7): 10888-10898.
