Polymorphism in ASCL1 target gene DDC is associated with clinical outcomes of small cell lung cancer patients

Abstract

BackgroundAchaete‐scute homolog 1 (ASCL1) is a basic helix‐loop‐helix transcription factor and is essential in the differentiation of neuroendocrine cells and neural tissues. ASCL1 is frequently overexpressed in small cell lung cancer (SCLC) and plays a crucial role in the pathogenesis of SCLC.MethodsThis study was conducted to identify the association between single nucleotide polymorphisms (SNPs) in ASCL1 target genes and clinical outcomes of patients with SCLC after chemotherapy. A total of 261 patients diagnosed with SCLC were enrolled in this study. The association between 103 SNPs in 58 ASCL1 target genes and the response to chemotherapy and survival of patients with SCLC were analyzed.ResultsAmong the 103 SNPs, 10 SNPs were significantly associated with the response to chemotherapy, and 19 SNPs were associated with OS in multivariate analyses. Among these, Dopa Decarboxylase (DDC) rs12666409A>T was significantly associated with both a worse response to chemotherapy and worse OS (adjusted odds ratio [aOR] = 0.40, 95% CI = 0.18–0.90, P = 0.03; adjusted hazard ratio [aHR] = 1.52, 95% CI = 1.10–2.10, P = 0.01, respectively, under a dominant model). In a stage‐stratified analysis, the association was significant only in the extensive disease subgroup (aOR = 0.19, 95% CI = 0.06–0.60, P = 0.01; aHR = 1.73, 95% CI = 1.16–2.56, P = 0.01, respectively, under a dominant model), but not in the limited disease subgroup.ConclusionThe results of our study suggest that DDC rs12666409A>T may be useful markers for predicting the clinical outcomes of patients with SCLC undergoing chemotherapy.

Multi-omics profiles refine L-dopa decarboxylase (DDC) as a reliable biomarker for prognosis and immune microenvironment of clear cell renal cell carcinoma

“…However, in prostate cancer, the higher expression of DDC was associated with advanced stages, higher Gleason scores, biochemical recurrence, and short disease-free survival (DFS) ( 22 ). Also, the role of DDC has been investigated in the development of colorectal cancer ( 23 ), small cell lung cancer ( 24 ), and gastric cancer ( 25 ). However, the prognostic value and underlying mechanism caused by aberrant L-dopa decarboxylase expression have not been systematically elucidated in ccRCC.…”

Genetic variants of NEUROD1 target genes are associated with clinical outcomes of small‐cell lung cancer patients

“…The study population has been described in our previous study. 19 Briefly, 261 patients diagnosed with SCLC between 1997 and 2017 at the Kyungpook National University Hospital (KNUH) who received at least two cycles of the EP regimen or the IP regimen chemotherapy as first line treatment were enrolled. Patients treated with concurrent chemoradiotherapy were excluded because radiotherapy may affect the evaluation of chemotherapy response.…”

MBD5 and MBD6 stabilize the BAP1 complex and promote BAP1-dependent cancer

“…4G, Additional file 2: Fig. S4G, H), which are all critical genes for SCLC development [17,33,34]. Finally, to determine the impact of MBD6 on SCLC tumor growth in vivo, we injected NCI-H510 human SCLC cell lines transduced with either non-targeting CRISPR-Cas9 or two distinct MBD6 sgRNAs into the right flank of nude mice.…”