DCBLD1 is associated with the integrin signaling pathway and has prognostic value in non-small cell lung and invasive breast carcinoma

Guillaume B Cardin,Francis Rodier,Monique Bernard,Apostolos Christopoulos

doi:10.1038/s41598-021-92090-6

Guillaume B Cardin, Francis Rodier + Show 2 more

Open Access

https://doi.org/10.1038/s41598-021-92090-6

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Abstract

Germline single nucleotide polymorphisms in the promoter region of the DCBLD1 gene are associated with non-smoking cases of both non-small cell lung carcinoma (NSCLC) and human papillomavirus-negative head and neck cancer. However the clinical relevance and function of DCBLD1 remain unclear. This multicenter retrospective study was designed to evaluate the prognostic value and function of DCBLD1 in the four main solid cancers: NSCLC, invasive breast carcinoma, colorectal adenocarcinoma and prostate adenocarcinoma. We included the following cohorts: GSE81089 NSCLC, METABRIC invasive breast carcinoma, GSE14333 colorectal adenocarcinoma, GSE70770 prostate adenocarcinoma and The Cancer Genome Atlas (TCGA) Firehose Legacy cohorts of all four cancers. DCBLD1 gene expression was associated with a worse overall survival in multivariate analyses for both NSCLC cohorts (TCGA: P = 0.03 and GSE81089: P = 0.04) and both invasive breast carcinoma cohorts (TCGA: P = 0.02 and METABRIC: P < 0.001). Patients with high DCBLD1 expression showed an upregulation of the integrin signaling pathway in comparison to those with low DCBLD1 expression in the TCGA NSCLC cohort (FDR = 5.16 × 10–14) and TCGA invasive breast carcinoma cohort (FDR = 1.94 × 10–05).

Highlights

Germline single nucleotide polymorphisms in the promoter region of the DCBLD1 gene are associated with non-smoking cases of both non-small cell lung carcinoma (NSCLC) and human papillomavirusnegative head and neck cancer
Studies have reported an association between single nucleotide polymorphisms (SNPs) in the DCBLD1 promoter region and higher risks of never-smoking cancers for human papillomavirus-negative head and neck squamous cell carcinoma (HNSCC), lung cancer, and female lung adenocarcinoma (LUAD)[2,3,4]
NSCLC, invasive breast carcinoma, colorectal adenocarcinoma and prostate adenocarcinoma were each represented by two cohorts for the analysis of DCBLD1 gene expression and cancer outcome

Summary

Introduction

Germline single nucleotide polymorphisms in the promoter region of the DCBLD1 gene are associated with non-smoking cases of both non-small cell lung carcinoma (NSCLC) and human papillomavirusnegative head and neck cancer. The clinical relevance and function of DCBLD1 remain unclear This multicenter retrospective study was designed to evaluate the prognostic value and function of DCBLD1 in the four main solid cancers: NSCLC, invasive breast carcinoma, colorectal adenocarcinoma and prostate adenocarcinoma. Patients with high DCBLD1 expression showed an upregulation of the integrin signaling pathway in comparison to those with low DCBLD1 expression in the TCGA NSCLC cohort (FDR = 5.16 × 1 0–14) and TCGA invasive breast carcinoma cohort (FDR = 1.94 × 1 0–05). SNPs in this locus were associated with higher DCBLD1 expression in HNSCC and lung c ancer[2,5], and with overall survival in two other studies, one on female non-smoking patients with lung cancer, and another in non-small cell lung carcinoma (NSCLC)[4,6]. The FLAG immunoprecipitate revealed that the majority of DCBLD1 interactors were adaptor proteins and proteins associated with actin dynamics[15]

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