Sharma Parul, Singh Navneet, Sharma Siddharth
Department of Biotechnology, Thapar Institute of Engineering & Technology, Patiala, India.
Department of Pulmonary Medicine, Post Graduate Institute of Medical Education & Research, Chandigarh, India.
J Gene Med. 2023 Jan;25(1):e3460. doi: 10.1002/jgm.3460. Epub 2022 Nov 14.
ABC transporters are membrane proteins expressed in the lungs and are crucial for efflux of various chemotherapeutic agents. Polymorphisms of ABC transporters have a certain impact on the transporter activity because their expression levels may influence the extent and longevity of chemotherapeutic drug outflow, affecting patient outcomes. The present study aimed to assess the impact of ABCB1, ABCC1/2, and ABCG2 gene variants in predicting prognosis and clinical outcomes in lung carcinoma patients.
In total, 502 lung cancer patients undergoing platinum-based chemotherapy were recruited in this prospective study. Genotyping of ABCB1 (C T, C T, and G T/A), ABCC1 (G A and G A), ABCC2 (G A), and ABCG2 (C A) polymorphisms in Northern Indian lung carcinoma patients were evaluated using polymerase chain reaction-restriction fragment length polymorphism analysis.
Poor survival outcomes were noted in patients carrying a heterozygous genotype (CT) for the ABCB1 C T polymorphism compared to the wild-type genotype (CC) (p = 0.04). The mutant genotype (AA) for ABCC1 G A exhibited a lower median survival time compared to the reference genotype (GG) (p = 0.009). Lower survival was observed in individuals carrying a heterozygous genotype (GA) for ABCC2 G A polymorphism compared to the wild-type genotype (GG) (p = 0.017). Small cell lung cancer patients with the ABCB1 G A polymorphism having a heterozygous genotype (GA) showed poor survival compared to the wild-type genotype (GG) (p = 0.03). For ABCC1 G A, adenocarcinoma patients having a mutant genotype (AA) had reduced survival compared to the wild-type (GG) genotype (p = 0.03). For ABCB1 C T, individuals carrying a heterozygous (CT) (p = 0.018) and mutant (TT) genotype (p = 0.007) had poor survival compared to the wild-type (CC) genotype in patients treated with pemetrexed and cisplatin. The patients administered cisplatin and irinotecan and having mutant alleles (AA) for the ABCB1 G A polymorphism showed a lower survival compared to the individuals carrying wild-type alleles (GG) (p = 0.009).
Our findings suggest that ABCB1 C T, ABCB1 C T, ABCB1 G A, ABCC1 G A, and ABCC2 G A are involved in predicting prognosis. Genotyping of the ABC polymorphism is essential for predicting prognosis in lung carcinoma patients.
ABC转运蛋白是在肺部表达的膜蛋白，对多种化疗药物的外排至关重要。ABC转运蛋白的多态性对转运蛋白活性有一定影响，因为它们的表达水平可能会影响化疗药物流出的程度和持续时间，从而影响患者的预后。本研究旨在评估ABCB1、ABCC1/2和ABCG2基因变异对预测肺癌患者预后和临床结局的影响。
本项前瞻性研究共纳入502例接受铂类化疗的肺癌患者。采用聚合酶链反应-限制性片段长度多态性分析评估印度北部肺癌患者中ABCB1（C>T、C>T和G>T/A）、ABCC1（G>A和G>A）、ABCC2（G>A）和ABCG2（C>A）多态性的基因分型。
与野生型基因型（CC）相比，携带ABCB1 C>T多态性杂合基因型（CT）的患者生存结局较差（p = 0.04）。ABCC1 G>A的突变基因型（AA）与参考基因型（GG）相比，中位生存时间较低（p = 0.009）。与野生型基因型（GG）相比，携带ABCC2 G>A多态性杂合基因型（GA）的个体生存率较低（p = 0.017）。具有ABCB1 G>A多态性杂合基因型（GA）的小细胞肺癌患者与野生型基因型（GG）相比生存较差（p = 0.03）。对于ABCC1 G>A，腺癌患者中具有突变基因型（AA）的患者与野生型（GG）基因型相比生存率降低（p = 0.03）。对于ABCB1 C>T，在接受培美曲塞和顺铂治疗的患者中，携带杂合子（CT）（p = 0.018）和突变（TT）基因型（p = 0.007）的个体与野生型（CC）基因型相比生存较差。接受顺铂和伊立替康治疗且具有ABCB1 G>A多态性突变等位基因（AA）的患者与携带野生型等位基因（GG）的个体相比生存率较低（p = 0.009）。
我们的研究结果表明，ABCB1 C>T、ABCB1 C>T、ABCB1 G>A、ABCC1 G>A和ABCC2 G>A参与预测预后。ABC多态性的基因分型对于预测肺癌患者的预后至关重要。
