Kaur Ishmeet, Kansal Heena, Singh Sidhartha, Singh Navneet, Sharma Siddharth
Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab, 147004, India.
Department of Biosciences and Bioengineering, D Y Patil International University, Akurdi, Pune, Maharashtra, India.
Clin Transl Oncol. 2025 Jun;27(6):2605-2619. doi: 10.1007/s12094-024-03800-1. Epub 2024 Nov 28.
Telomerase has been linked to aging and cancer. The MNS16A polymorphism in the hTERT gene plays a significant role in modulating telomerase activity and highlights the complexity of telomere-related genetics in cancer research.
We genotyped 401 lung-cancer samples treated with platinum-based chemotherapy to identify the MNS16A polymorphism. We assessed overall survival using the Kaplan-Meier method and Cox regression analysis for adjusted hazard ratios. Stratified analyses evaluated risks for subgroups based on clinicopathologic parameters, outcomes, and toxicity calculated.
Our findings show no significant link between MNS16A polymorphism and lung-cancer survival. However, in squamous cell carcinoma (SQCC) patients, the SS genotype was associated with poorer survival (p = 0.004). Patients with LS + SS genotypes responded better to gemcitabine in univariate (p = 0.003) and multivariate analyses (p = 0.014). The LS genotype was linked to a lower risk of progression to stage 4 (p = 0.011) and metastasis (p = 0.015) but an increased risk of T4 tumor size (p = 0.026). No significant correlations were found between MNS16A polymorphism and treatment-related toxicities.
The MNS16A polymorphism does not significantly impact overall lung-cancer survival but affects specific subgroups, influencing certain lung-cancer subtypes and treatment responses while having limited predictive value for overall outcomes or toxicity risks.
端粒酶与衰老和癌症相关。hTERT基因中的MNS16A多态性在调节端粒酶活性方面发挥着重要作用,并凸显了癌症研究中端粒相关遗传学的复杂性。
我们对401例接受铂类化疗的肺癌样本进行基因分型,以确定MNS16A多态性。我们使用Kaplan-Meier方法和Cox回归分析评估总生存期,以调整风险比。分层分析根据临床病理参数、结果和计算出的毒性评估亚组风险。
我们的研究结果表明,MNS16A多态性与肺癌生存率之间没有显著关联。然而,在鳞状细胞癌(SQCC)患者中,SS基因型与较差的生存率相关(p = 0.004)。在单变量(p = 0.003)和多变量分析(p = 0.014)中,LS + SS基因型的患者对吉西他滨反应更好。LS基因型与进展至4期(p = 0.011)和转移(p = 0.015)的风险较低相关,但与T4肿瘤大小增加的风险相关(p = 0.026)。未发现MNS16A多态性与治疗相关毒性之间存在显著相关性。
MNS16A多态性对肺癌总体生存率没有显著影响,但会影响特定亚组,影响某些肺癌亚型和治疗反应,而对总体结果或毒性风险的预测价值有限。