ArticleJournal of translational medicine2019
Somatic mutation of DNAH genes implicated higher chemotherapy response rate in gastric adenocarcinoma patients.
Article in Journal of translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 51 citations in OpenAlex.
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- Identification of hub genes associated with head and neck squamous cell carcinoma by integrated bioinformatics approach and RNA-seq validation analysis.American journal of cancer research · 2023Article
- Cross-species identification of cancer resistance-associated genes that may mediate human cancer risk.Science advances · 2022Article
- Impact of neoadjuvant chemotherapy on somatic mutation status in high-grade serous ovarian carcinoma.Journal of ovarian research · 2022Article
- The regulatory landscape of retinoblastoma: a pathway analysis perspective.Royal Society open science · 2022Article
- Clinical detection, diagnosis and treatment of morphological abnormalities of sperm flagella: A review of literature.Frontiers in genetics · 2022Review
- Somatic Mutation of FAT Family Genes Implicated Superior Prognosis in Patients With Stomach Adenocarcinoma.Frontiers in medicine · 2022Article
- Whole genome sequencing identifies rare germline variants enriched in cancer related genes in first degree relatives of familial pancreatic cancer patients.Clinical genetics · 2021Article
- Changes in Protein Structural Motifs upon Post-Translational Modification in Kidney Cancer.Diagnostics (Basel, Switzerland) · 2021Article
- Machine Learning-Based Comparative Analysis of Pan-Cancer and Pan-Normal Tissues Identifies Pan-Cancer Tissue-Enriched circRNAs Related to Cancer Mutations as Potential Exosomal Biomarkers.Frontiers in oncology · 2021Article
- Immunological classification of gliomas based on immunogenomic profiling.Journal of neuroinflammation · 2020Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe dynein axonemal heavy chain (DNAH) family of genes encode the dynein axonemal heavy chain, which is involved in cell motility. Genomic variations of DNAH family members have been frequently reported in diverse kinds of malignant tumors. In this study, we analyzed the genomic database to evaluate the mutation status of DNAH genes in gastric adenocarcinoma and further identified the significance of mutant DNAH genes as effective molecular biomarkers for predicting chemotherapy response in gastric cancer patients.
methodsWe analyzed the clinical and genomic data of gastric cancer patients published in The Cancer Genome Atlas (TCGA) project. Data on chemotherapy response, overall survival (OS) and chemotherapy-free survival were retrieved. Then, we verified the results via targeted sequencing of gastric cancer patients with similar clinical characteristics but different chemotherapeutic outcomes.
resultsIn total, 132 gastric adenocarcinoma patients undergoing chemotherapy treatment from TCGA were included in our study. Somatic mutations in all 13 members of the DNAH family of genes were associated with different chemotherapy responses. Compared with patients with wild-type DNAH genes (n = 59), a significantly higher proportion of those with mutations in DNAH genes (n = 73) (55.9% vs 80.8%) responded to chemotherapy (P = 0.002). Moreover, DNAH mutations were correlated with significantly better OS (P = 0.027), chemotherapy-free survival (P = 0.027), fluoropyrimidine-free survival (P = 0.048) and platinum-free survival (P = 0.014). DNAH mutation status was an independent risk factor for OS (P = 0.015), chemotherapy-free survival (P = 0.015) and platinum-free survival (P = 0.011). We identified somatic mutations in 27 (42.2%) of the 64 stage III gastric adenocarcinoma patients receiving fluoropyrimidine-based chemotherapy by targeted exon sequencing with strict screening conditions. In our own cohort, a significantly higher proportion of patients (n = 32) with DNAH mutations than patients with wild-type DNAH genes (n = 32) had a good prognosis (OS > 48 months) (70.4% vs 35.1%) (P = 0.005).
conclusionsDynein axonemal heavy chain gene mutations contribute positively to chemotherapy sensitivity in gastric cancer patients.
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