Single-nucleotide polymorphism rs41736 located in MET was significantly associated with prognosis of small cell lung cancer patients

Abstract

MET has been suggested to have an intimate relationship with small cell lung cancer (SCLC) and might be a promising therapeutic target. To date, relatively limited reports have been explored on MET mutational status in SCLC patients. To investigate the relationship between MET mutations and SCLC, 68 Chinese patients surgically treated for SCLC were enrolled. MET mutational analyses were performed in tumors, adjacent normal tissues as well as in lymph nodes with no metastasis nonadherent to tumor tissues using Sanger sequencing after PCR. The same mutation types were found in tumors, adjacent normal tissues as well as lymph nodes, including the only missense mutation N375S encoding semaphorin domain in exon 2 in 4 patients (5.9%), one single-nucleotide polymorphism (SNP) rs35775721: C>T also encoding semaphorin domain as heterozygous in 10 cases (14.7%) and another SNP rs41736: C>T encoding tyrosine kinase domain in exon 20 existing in 49 cases (72.1%). In survival analysis, the wild genotype CC-carriers of rs41736 conferred a significantly shorter progression-free survival (PFS) and overall survival (OS) compared to CT + TT-carriers (HR 0.455, 95% CI 0.229-0.904; HR 0.226, 95% CI 0.099-0.515, for PFS and OS, respectively) in limited-stage SCLC patients. We also found that the lymph node status was significantly associated with OS, and the shorter OS was present in positive group (HR 2.187, 95% CI 1.170-4.088). In this study, rs41736 polymorphism of MET was first found to be associated with prognosis of limited-stage SCLC patients and could be considered as a prognostic marker for limited-stage SCLC.

Association of PTEN Gene SNPs rs2299939 With PFS in Patients With Small Cell Lung Cancer Treated With Early Radiotherapy

“…Single-nucleotide polymorphism is the third generation of molecular markers of genetic variation, which is mainly used to study the differences in susceptibility of disease and sensitivity to different medication and treatment methods. To date, studies on relationship between lung cancer and SNPs mainly focused on NSCLC, and not much on SCLC (Knoefel et al, 2011;Gu et al, 2012;Szondy et al, 2012;Cao et al, 2014).…”

Association between miR-199a rs74723057 and MET rs1621 polymorphisms and the risk of hepatocellular carcinoma

“…Ueki et al found that HCC patients with high MET expression had a shorter 5-year survival than those with low MET expression [20]. Recently variants in MET have been reported to be associated with the prognosis of various human cancers, such as lung cancer and gastric cancer [30, 31]. Cao [30] et al found that compared with small cell lung cancer (SCLC) patients who carried the CT/TT genotypes of MET rs41736, those SCLC patients who carried the wild-genotype CC tended to have a shorter progression-free survival and overall survival.…”