Saluja Sundeep S, Sharma Abhay K, Nekarakanti Phani K, Kumar Arun, Ahmad Ejaj, Husain Syed A
Central Molecular Lab, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India.
Department of Biosciences, Jamia Millia Islamia, New Delhi, India.
J Clin Exp Hepatol. 2024 Sep-Oct;14(5):101410. doi: 10.1016/j.jceh.2024.101410. Epub 2024 Apr 12.
Gallbladder cancer (GBC) is a biologically aggressive malignancy requiring appropriate biomarkers to improve its outcome. Role of ABC transporters (ABCB1 and ABCG2) has been linked to cancer aggressiveness, tumorigenesis and multidrug resistance. Herein, we studied the prognostic implication of ABCB1 and ABCG2 in GBC.
Fresh tissue (tumour & normal) samples collected from 54 patients who underwent R0 resection, were analysed for mRNA and protein expression of ABCB1 and ABCG2 by quantitative Real-Time PCR and western blotting, respectively, in this prospective study. The molecular findings were correlated with clinical-pathological parameters using χ2 and fisher exact test. The molecular changes in ABCB1 and ABCG2 were analysed for predicting overall survival (OS), disease-free survival (DFS) and response to chemotherapy using Kaplan-Meier log-rank test and Cox regression multivariate analysis.
The mean age of the cohort was 50 ± 13.2 with 26 (48.1%) in patients having early stage gallbladder cancer (GBC). Over-expression of ABCB1 and ABCG2 was noted in 32/54 (59%) and 40/54 (74%) cases, respectively. The protein expression of ABCB1(P-glycoprotein) and ABCG2 (BCRP) was higher in 27/54 (50%) and 37/54 (59%) cases, respectively. The mean OS and DFS was 20.7 ± 11.5 and 19.3 ± 12.2 months at median follow-up of 24 months. The TNM stage, lymph node metastasis, and presence of gallstone were significant factors for predicting OS and DFS on multivariate analysis. Both ABCB1 and ABCG2 did not show any significant correlation with OS and DFS with similar incidences of late death and recurrence among over-expression and down-expression. Sub-group comparison suggests that change in expression pattern of ABCB1 and ABCG2 may not affect response to chemotherapy in GBC.
Altered expression of ABCB1 and ABCG2 may not be a useful prognostic marker for survival or response to chemotherapy in GBC. Presently, histo-pathological characteristics and associated gallstones are the important predictors for survival and recurrence in GBC.
胆囊癌（GBC）是一种具有生物学侵袭性的恶性肿瘤，需要合适的生物标志物来改善其治疗结果。ABC转运蛋白（ABCB1和ABCG2）的作用与癌症侵袭性、肿瘤发生和多药耐药性有关。在此，我们研究了ABCB1和ABCG2在胆囊癌中的预后意义。
在这项前瞻性研究中，分别通过定量实时PCR和蛋白质印迹法分析了从54例行R0切除的患者中收集的新鲜组织（肿瘤和正常）样本中ABCB1和ABCG2的mRNA和蛋白质表达。使用χ2检验和Fisher精确检验将分子学结果与临床病理参数进行相关性分析。使用Kaplan-Meier对数秩检验和Cox回归多变量分析，分析ABCB1和ABCG2的分子变化对总生存期（OS）、无病生存期（DFS）和化疗反应的预测作用。
该队列的平均年龄为50±13.2岁，其中26例（48.1%）为早期胆囊癌患者。ABCB1和ABCG2的过表达分别在32/54例（59%）和40/54例（74%）中被观察到。ABCB1（P-糖蛋白）和ABCG2（乳腺癌耐药蛋白）的蛋白质表达分别在27/54例（50%）和37/54例（59%）中更高。在中位随访24个月时，平均总生存期和无病生存期分别为20.7±11.5个月和19.3±12.2个月。多变量分析显示，TNM分期、淋巴结转移和胆结石的存在是预测总生存期和无病生存期的重要因素。ABCB1和ABCG2均与总生存期和无病生存期无显著相关性，过表达和低表达组的晚期死亡和复发发生率相似。亚组比较表明，ABCB1和ABCG2表达模式的改变可能不会影响胆囊癌的化疗反应。
ABCB1和ABCG2表达的改变可能不是胆囊癌生存或化疗反应的有用预后标志物。目前，组织病理学特征和相关胆结石是胆囊癌生存和复发的重要预测指标。
