Association of well-characterized lung cancer lncRNA polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response

Tumour Biol. 2016 Jun;37(6):8349-58. doi: 10.1007/s13277-015-4497-5. Epub 2016 Jan 5.

Abstract

Long non-coding RNAs (lncRNAs) play important roles in carcinogenesis and drug efficacy. Platinum-based chemotherapy is first-line treatment for lung cancer chemotherapy. In this study, we aimed to investigate the association of well-characterized lung cancer lncRNA genetic polymorphisms with the lung cancer susceptibility and platinum-based chemotherapy response. A total of 498 lung cancer patients and 213 healthy controls were recruited in the study. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Thirteen polymorphisms in HOXA distal transcript antisense RNA (HOTTIP), HOX transcript antisense intergenic RNA (HOTAIR), H19, CDKN2B antisense RNA 1 (ANRIL), colon cancer-associated transcript 2 (CCAT2), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and maternally expressed gene 3 (MEG3) genes were genotyped by allele-specific MALDI-TOF mass spectrometry. We found that patients with HOTTIP rs5883064 C allele or rs1859168 A allele had increased lung cancer risk (P = 0.01, P = 0.01, respectively). CCAT2 rs6983267 (P = 0.02, adenocarcinoma) and H19 rs2107425 (P = 0.02, age under 50 years) showed strong relationship with lung cancer susceptibility. CCAT2 rs6983267, H19 rs2839698, MALAT1 rs619586, and HOTAIR rs7958904 were associated with platinum-based chemotherapy response in dominant model ((P = 0.02, P = 0.04, P = 0.04, P = 0.01, respectively). ANRIL rs10120688 (P = 0.02, adenocarcinoma) and rs1333049 (P = 0.04, small-cell lung cancer), H19 rs2107425 (P = 0.02, small-cell lung cancer) and HOTAIR rs1899663 (P = 0.03, male; P = 0.03, smoker) were associated with response to platinum-based chemotherapy. HOTTIP, CCAT2, H19, HOTAIR, MALATI, ANRIL genetic polymorphisms were significantly associated with lung cancer susceptibility or platinum-based chemotherapy response. They may be potential clinical biomarkers to predict lung cancer risk and platinum-based chemotherapy response.

Keywords: Long non-coding RNA; Lung cancer; Platinum-based chemotherapy response; Polymorphism; Susceptibility.

MeSH terms

  • Alleles
  • Antineoplastic Agents / therapeutic use*
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Organoplatinum Compounds / therapeutic use*
  • Polymorphism, Single Nucleotide*
  • RNA, Long Noncoding / genetics*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Antineoplastic Agents
  • CDKN2B antisense RNA, human
  • H19 long non-coding RNA
  • HOTAIR long untranslated RNA, human
  • MALAT1 long non-coding RNA, human
  • Organoplatinum Compounds
  • RNA, Long Noncoding
  • long non-coding RNA CCAT2, human
  • long noncoding RNA HOTTIP, human