Novel genetic variants in genes of the Fc gamma receptor-mediated phagocytosis pathway predict non-small cell lung cancer survival.
Abstract
Background:Both antibody-dependent cellular cytotoxicity and phagocytosis activate
innate immunity, and the Fc gamma receptor (FCGR)-mediated phagocytosis is an integral
part of the process. We assessed associations between single-nucleotide polymorphisms
(SNPs) in FCGR-related genes and survival of patients with non-small cell lung cancer
(NSCLC). Methods:We evaluated associations between 24,734 (SNPs) in 97 FCGR-related
genes and survival of 1,185 patients with NSCLC using a published genome-wide association
study (GWAS) dataset from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer
Screening Trial and validated the results in another independent dataset of 894 NSCLC
patients. Results:In the single-locus analysis with Bayesian false discovery probability
(BFDP) for multiple testing correction, we found 1,084 SNPs to be significantly associated
overall survival (OS) (P<0.050 and BFDP ≤0.80), of which two independent SNPs (PLCG2
rs9673682 T>G and PLPP1 rs115613985 T>A) were further validated in another GWAS dataset
of 894 patients from the Harvard Lung Cancer Susceptibility (HLCS) Study, with combined
allelic hazards ratios for OS of 0.87 [95% confidence interval (CI): 0.81-0.94 and
P=5.90×10-4] and 1.18 (95% CI: 1.08-1.29 and 1.32×10-4, respectively). Expression
quantitative trait loci analysis showed that the rs9673682 G allele was significantly
correlated with increased mRNA expression levels of PLCG2 in 373 transformed lymphoblastoid
cell-lines (P=7.20×10-5). Additional evidence from differential expression analysis
further supported a tumor-suppressive effect of PLCG2 on OS of patients with lung
cancer, with lower mRNA expression levels in both lung squamous carcinoma and adenocarcinoma
than in adjacent normal tissues. Conclusions:Genetic variants in PLCG2 of the FCGR-mediated
phagocytosis pathway may be promising predictors of NSCLC survival, possibly through
modulating gene expression, but additional investigation of the molecular mechanisms
of PLPP1 rs115613985 is warranted.
Type
Journal articleSubject
Fc gamma receptor (FCGR)Non-small cell lung cancer (NSCLC)
genome-wide association study (GWAS)
single-nucleotide polymorphism (SNP)
survival
Permalink
https://hdl.handle.net/10161/21214Published Version (Please cite this version)
10.21037/tlcr-19-318Publication Info
Qian, Danwen; Liu, Hongliang; Zhao, Lingling; Wang, Xiaomeng; Luo, Sheng; Moorman,
Patricia G; ... Wei, Qingyi (2020). Novel genetic variants in genes of the Fc gamma receptor-mediated phagocytosis pathway
predict non-small cell lung cancer survival. Translational lung cancer research, 9(3). pp. 575-586. 10.21037/tlcr-19-318. Retrieved from https://hdl.handle.net/10161/21214.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
Collections
More Info
Show full item recordScholars@Duke
Sheng Luo
Professor of Biostatistics & Bioinformatics
Patricia Gripka Moorman
Professor Emeritus in Family Medicine and Community Health
Dr. Moorman's research focuses on the epidemiology of women's health issues. Her work
includes research on ovarian cancer, breast cancer and hysterectomy. Areas of particular
interest include disparities in cancer risk factors and outcomes and the effects of
hysterectomy on ovarian function. As part of the Duke Evidence Synthesis group, she
has also been involved in systematic reviews and meta-analyses related to ovarian
cancer, breast cancer and infertility.
Edward F. Patz Jr.
James and Alice Chen Distinguished Professor of Radiology
There are numerous ongoing clinical studies primarily focused on the early detection
of cancer.
The basic science investigations in our laboratory concentration on three fundamental
translational areas, 1) Development of molecular imaging probes - We have used several
different approaches to develop novel imaging probes that characterize and phenotype
tumors. 2) Discovery of novel lung cancer biomarkers - We ex
Qingyi Wei
Professor in Population Health Sciences
Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director
for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology
and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally
recognized epidemiologist focused on the molecular and genetic epidemiology of head
and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and
genetic determinants for the DNA repair deficient phenotype and
Alphabetical list of authors with Scholars@Duke profiles.

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info