Genetic Associations of Visfatin Polymorphisms with EGFR Status and Clinicopathologic Characteristics in Lung Adenocarcinoma

Int J Environ Res Public Health. 2022 Nov 17;19(22):15172. doi: 10.3390/ijerph192215172.

Abstract

Lung adenocarcinoma (LUAD) is the most common histologic type of lung cancer. Mutations of the epidermal growth factor receptor (EGFR) gene are among the most common genetic alterations in LUAD and are the targets of EGFR tyrosine kinase inhibitors. The enzyme visfatin is involved in the generation of the oxidized form of nicotinamide adenine dinucleotide (NAD+) and regulation of intracellular adenosine triphosphate (ATP), critical processes in cancer cell survival and growth. This study explored the relationship between visfatin single nucleotide polymorphisms (SNPs) with EGFR status and the clinicopathologic development of LUAD in a cohort of 277 Taiwanese men and women with LUAD. Allelic discrimination of four visfatin SNPs rs11977021, rs61330082, rs2110385 and rs4730153 was determined using a TaqMan Allelic Discrimination assay. We observed higher prevalence rates of advanced (T3/T4) tumors and distant metastases in EGFR wild-type patients carrying the rs11977021 CT + TT and rs61330082 GA + AA genotypes, respectively, compared with patients carrying the CC and GG genotypes. EGFR wild-type patients carrying the rs11977021 CT + TT genotypes were also more likely to develop severe (stage III/IV) malignancy compared with patients carrying the CC genotype. An analysis that included all patients found that the association persisted between the rs11977021 CT + TT and rs61330082 GA + AA genotypes and the development of T3/T4 tumors compared with patients carrying the rs11977021 CC and rs61330082 GG genotypes. In conclusion, these data indicate that visfatin SNPs may help to predict tumor staging in LUAD, especially in patients with EGFR wild-type status.

Keywords: nicotinamide phosphoribosyltransferase; non-small cell lung cancer; pre-B-cell colony-enhancing factor; single nucleotide polymorphism; visfatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Lung Neoplasms*
  • Male
  • Nicotinamide Phosphoribosyltransferase / genetics
  • Protein Kinase Inhibitors

Substances

  • EGFR protein, human
  • ErbB Receptors
  • Nicotinamide Phosphoribosyltransferase
  • Protein Kinase Inhibitors
  • nicotinamide phosphoribosyltransferase, human

Grants and funding

This work was supported by grant from the Ministry of Science and Technology of Taiwan (MOST-109-2320-B-341-002-; MOST 110-2320-B-039-022-MY3), National Science and Technology Council of Taiwan (NSTC 111-2320-B-468-006-), China Medical University (CMUBHR109-007; CMU102-S-04; CMU111-NSTC-03), China Medical University Hospital (DMR-112-146), and Asia University Hospital (10951002; 11051008).