El-Hamamsy Manal, Ghali Ramy R, Saad Amr S, Shaheen Sara M, Salem Ahmed M
Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Department of Clinical Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Onco Targets Ther. 2016 Nov 7;9:6857-6863. doi: 10.2147/OTT.S115631. eCollection 2016.
FAS-670 A>G (rs1800682) and FASL-844 C>T (rs763110) polymorphisms have been previously correlated with clinical outcome of non-small cell lung cancer (NSCLC) and breast and bladder cancers. We investigated the influence of these polymorphisms on clinical outcome of malignant pleural mesothelioma (MPM) patients.
In this cohort study (NCT02269878), 68 epithelioid MPM Egyptian patients treated with first-line platinum-based chemotherapy were recruited in the period between April 2014 and May 2015. The genotype analysis was performed using TaqMan single-nucleotide polymorphism genotyping assay. The association between the selected polymorphisms and response rate, progression-free survival (PFS) and overall survival (OS) at 18 months was evaluated.
The median age of patients was 55 years and 45.6% of them received platinum in combination with pemetrexed, while 54.4% received platinum in combination with gemcitabine. FASL-844 CC genotype was more common than expected in early-stage tumor (=0.042). It was found that there was no association between the investigated polymorphisms and response rate or 18-month OS. However, the PFS rate at 18 months for FASL-844 CC genotype carriers was 45% versus 10.6% for FASL-844 CT/TT genotypes carriers (log-rank: 6.2; =0.013). Also, the number of platinum-based cycles and tumor stage were found to be significant variables for PFS by univariate analysis (≤0.001 and =0.006, respectively). Stratified Cox regression showed that the carriers of FASL-844 CT/TT genotypes were still more susceptible to disease progression than carriers of FASL-844 CC genotype (adjusted HR =3.77, 95% CI: 1.34-10.62, =0.012).
The results of this study suggest that FASL-844 C/T polymorphism could predict PFS in MPM patients receiving platinum-based chemotherapy; therefore, this should be further evaluated as a potential marker for the prediction of clinical outcome in patients with MPM.
FAS-670 A>G（rs1800682）和FASL-844 C>T（rs763110）多态性先前已与非小细胞肺癌（NSCLC）、乳腺癌和膀胱癌的临床结局相关。我们研究了这些多态性对恶性胸膜间皮瘤（MPM）患者临床结局的影响。
在这项队列研究（NCT02269878）中，2014年4月至2015年5月期间招募了68例接受一线铂类化疗的埃及上皮样MPM患者。使用TaqMan单核苷酸多态性基因分型检测进行基因分型分析。评估所选多态性与缓解率、无进展生存期（PFS）和18个月总生存期（OS）之间的关联。
患者的中位年龄为55岁，其中45.6%接受铂类与培美曲塞联合治疗，54.4%接受铂类与吉西他滨联合治疗。FASL-844 CC基因型在早期肿瘤中比预期更常见（P=0.042）。发现所研究的多态性与缓解率或18个月OS之间无关联。然而，FASL-844 CC基因型携带者18个月时的PFS率为45%，而FASL-844 CT/TT基因型携带者为10.6%（对数秩检验：6.2；P=0.013）。此外，单因素分析发现铂类化疗周期数和肿瘤分期是PFS的显著变量（分别为P≤0.001和P=0.006）。分层Cox回归显示，FASL-844 CT/TT基因型携带者仍比FASL-844 CC基因型携带者更易发生疾病进展（调整后HR=3.77，95%CI：1.34-10.62，P=0.012）。
本研究结果表明，FASL-844 C/T多态性可预测接受铂类化疗的MPM患者的PFS；因此，应进一步评估其作为MPM患者临床结局预测潜在标志物的价值。
