title: 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.
authors.affiliation: Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai, 200433, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Cao
authors.forename: Xuan
authors.initials: X
authors.lastname: Hong
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Jia
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D006579:Heterozygote; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000601:surgery; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D017434:Protein Structure, Tertiary; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000601:surgery
chemical_list: D000970:Antineoplastic Agents; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met