title: MicroRNA-Related Polymorphisms in PI3K/Akt/mTOR Pathway Genes Are Predictive of Limited-Disease Small Cell Lung Cancer Treatment Outcomes.
abstract: The phosphoinositide-3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway plays an important role in cancer progression and treatment, including that of small cell lung cancer (SCLC), a disease with traditionally poor prognosis. Given the regulatory role of microRNA (miRNA) in gene expression, we examined the association of single nucleotide polymorphisms (SNPs) at miRNA-binding sites of genes in the mTOR pathway with the prognosis of patients with limited-disease SCLC. A retrospective study was conducted of 146 patients with limited-disease SCLC treated with chemoradiotherapy. Nine SNPs of six mTOR pathway genes were genotyped using blood samples. Cox proportional hazard regression modeling and recursive partitioning analysis were performed to identify SNPs significantly associated with overall survival. Three SNPs,MTOR: rs2536 (T>C),PIK3R1: rs3756668 (A>G), andPIK3R1: rs12755 (A>C), were associated with longer overall survival. Recursive partitioning analysis based on unfavorable genotype combinations of the rs2536 and rs3756668 SNPs classified patients into three risk subgroups and was internally validated with 1000 bootstrap samples. These findings suggest that miRNA-related polymorphisms in the PI3K/Akt/mTOR pathway may be valuable biomarkers to complement clinicopathological variables in predicting prognosis of limited-disease SCLC and to facilitate selection of patients likely to benefit from chemoradiotherapy.
authors.affiliation: Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Shenzhen Center, Shenzhen 100021, China.
authors.forename: Wei
authors.identifier: 0000-0002-9079-0792
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Wenjue
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Lipin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Men
authors.affiliation: Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Zhouguang
authors.identifier: 0000-0002-7189-4692
authors.initials: Z
authors.lastname: Hui
authors.affiliation: Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Zongmei
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Nan
authors.identifier: 0000-0001-7201-2930
authors.initials: N
authors.lastname: Bi
authors.affiliation: Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Luhua
authors.identifier: 0000-0002-5272-1681
authors.initials: L
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015203:Reproducibility of Results; D015398:Signal Transduction; D055752:Small Cell Lung Carcinoma / Q000235:genetics*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt