C3orf21 ablation promotes the proliferation of lung adenocarcinoma, and its mutation at the rs2131877 locus may serve as a susceptibility marker.

In this study, we investigated the role of C3orf21 gene polymorphism at the rs2131877 locus and its contribution to lung adenocarcinoma pathogenesis. Normal lung and tumor tissue sections were collected from fifteen patients with lung adenocarcinoma for chromosome 3 open reading frame 21 (C3orf21) genotype analysis. In addition, a retrospective analysis was performed to assess the association between C3orf21 genotype and tumor markers from patient samples used in our previously published study. In parallel, we also manipulated C3orf21 gene expression either by overexpressing or ablating it in a MSTO-211H human lung cancer cell line to further understand its contribution to cell proliferation, apoptosis and migration. Our results indicated that the patients with smoking history had a significantly increased mutation (rs2131877 T/C+C/C genotype) rate (p = 0.025), in addition to higher values for the CYF211 and NSE tumor markers (p = 0.014 and p = 0.031, respectively). The retrospective analysis also confirmed that the NSE marker value was higher in patients with a C3orf21 rs2131877 T/C+C/C genotype. Furthermore, our in vitro data indicated that C3orf21 ablation promoted lung cancer cell proliferation, inhibited apoptosis and accelerated cell migration. Overall, our study concluded that C30rf21 rs 2131877 T/C+C/C genotype patients may experience increased nicotine addiction and that C30rf21 can likely serve as a susceptibility marker for lung adenocarcinoma with a higher degree of malignancy.