Dataset Information

Somatic mutation of DNAH genes implicated higher chemotherapy response rate in gastric adenocarcinoma patients.

ABSTRACT:

Background

The 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.

Methods

We 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.

Results

In 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).

Conclusions

Dynein axonemal heavy chain gene mutations contribute positively to chemotherapy sensitivity in gastric cancer patients.

SUBMITTER: Zhu C

PROVIDER: S-EPMC6448266 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

Somatic mutation of DNAH genes implicated higher chemotherapy response rate in gastric adenocarcinoma patients.

Zhu Chunchao C Yang Qin Q Xu Jia J Zhao Wenyi W Zhang Zizhen Z Xu Danhua D Zhang Yeqian Y Zhao Enhao E Zhao Gang G

Journal of translational medicine 20190403 1

<h4>Background</h4>The 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 chemothera ...[more]

PMID: 30944005

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Project description:BackgroundTo investigate the association of axillary pathologic complete response (pCR) rate among breast cancer patients with pCR after neoadjuvant chemotherapy (NCT).MethodsThe retrospective clinical data of 1,903 patients who were treated with NCT between March, 2010 and December, 2018, were collected from one Chinese database and analyzed. The correlations between clinicopathological characteristics and breast pCR with axillary pCR were calculated by χ2 test. Binary logistic regression analysis was used for multivariate analysis. The relative risk of positive axillary nodes after NCT in patients with and without breast pCR was analyzed using a Cochran-Mantel-Haenszel (CMH) test stratified by initial N stage and tumor subtype.ResultsThe rate of axillary pCR was increased in the cases with initial cN0, Ki67 high expression, HR+HER2+/HR-HER2+/TN subtypes, and breast pCR. After NCT, the relative risk of nodal disease burden was 4.81 in patients without breast pCR compared with patients with breast pCR. The relative risk of positive nodal status in patients with cN0, cN1, cN2, and cN3 disease without vs. with breast pCR was 6.45, 4.88, 5.69 and 6.24, respectively. The relative risk of positive nodal status in patients with HR+HER2-, HR+HER2+, HR-HER2+, and TN disease was 4.02, 4.50, 3.82 and 4.18, respectively. Of cN0 patients with breast pCR, only 4 out of 44 (9%) with HER2-positive disease had 1 or 2 axillary lymph node metastases at final surgical pathology compared to 30 out of 98 (31%) of those without breast pCR. There was no evidence of positive nodal residue among all 21 patients (100%) with TN disease compared to 65% (36 of 55) of patients without breast pCR.ConclusionsNodal status is strongly correlated with breast pCR after NCT. Patients with initial cN0/1 TN/HER2 positive disease who achieve breast pCR at surgery have a low risk of nodal metastasis. These results suggest that the failure rate of missing positive lymph nodes among those patients was very low and that it is safe for such patients to undergo sentinel lymph node biopsy (SLNB) after NCT. This study also provides a theoretical basis for clinical trials focused on the avoidance of axillary surgery in selected patients.

Dataset Information

Somatic mutation of DNAH genes implicated higher chemotherapy response rate in gastric adenocarcinoma patients.

Background

Methods

Results

Conclusions

Publications

Somatic mutation of DNAH genes implicated higher chemotherapy response rate in gastric adenocarcinoma patients.

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