Delay in initiation of postoperative adjuvant chemotherapy with S-1 monotherapy and prognosis for gastric cancer patients: analysis of a multi-institutional dataset

Abstract Purpose The enzymes gamma-glutamyl hydrolase (GGH) and folylpolyglutamate synthetase (FPGS) regulate intracellular folate concentrations needed for cell proliferation, DNA synthesis, and repair. High GGH expression affects 5-FU thymidylate synthase (TS) inhibition and is a risk factor for various malignancies. Here, the clinical significance of GGH and FPGS expression was investigated in Stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1. Methods Surgical specimens of cancer tissue and adjacent normal mucosa, obtained from 253 patients with previously untreated gastric cancer, were examined. GGH and FPGS mRNA expression was measured by qPCR to evaluate their clinicopathological significance in gastric cancer patients after curative resection. Results While FPGS expression showed no significant differences between the cancerous and normal samples, GGH expression was higher in cancer tissue than in adjacent normal mucosa. High GGH expression was correlated with age, histological type, and vascular invasion. Overall survival (OS) of patients with high GGH mRNA expression was significantly poorer than of patients with low GGH expression. Multivariate analysis showed that high GGH expression was an independent prognostic factor of OS (HR: 2.58, 95% CI 1.29–5.16). Patients who received S-1 adjuvant treatment showed a significantly poor OS between high GGH/low FPGS and low GGH/high FPGS. Patients without adjuvant treatment showed no significant difference. Conclusion GGH expression was significantly higher in gastric cancer tissue than in adjacent normal mucosa. High GGH and low FPGS expression is a useful independent predictor of poor outcomes in stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1.

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ERCC1 expression is a predictor of survival in gastric cancer patients treated with surgery and adjuvant chemotherapy

The Chinese-German Journal of Clinical Oncology ◽

10.1007/s10330-011-0739-1 ◽

2011 ◽

Vol 10 (2) ◽

pp. 92-95 ◽

Cited By ~ 1

Author(s):

Qiang Li ◽

Chengxue Dang ◽

Zhigang Liu ◽

Ruifang Sun

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Ercc1 Expression ◽

Gastric Cancer Patients

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Which is better for gastric cancer patients, perioperative or adjuvant chemotherapy: a meta-analysis

BMC Cancer ◽

10.1186/s12885-016-2667-5 ◽

2016 ◽

Vol 16 (1) ◽

Cited By ~ 12

Author(s):

Jun-hua Zhao ◽

Peng Gao ◽

Yong-xi Song ◽

Jing-xu Sun ◽

Xiao-wan Chen ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Meta Analysis ◽

Gastric Cancer Patients

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Prognostic Indicators in Stage IV Surgically Treated Gastric Cancer Patients: A Retrospective Multi-Institutional Study

Digestive Surgery ◽

10.1159/000488775 ◽

2018 ◽

Vol 36 (4) ◽

pp. 331-339

Author(s):

Alberto Biondi ◽

Domenico D’Ugo ◽

Ferdinando Cananzi ◽

Stefano Rausei ◽

Federico Sicoli ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Residual Disease ◽

Stage Iv ◽

Long Term Results ◽

Stage Iv Gastric Cancer ◽

Short And Long Term ◽

Gastric Cancer Patients

Introduction: The role of gastric resection in treating metastatic gastric adenocarcinoma is controversial. In the present study, we reviewed the short- and long-term outcomes of stage IV patients undergoing surgery. Methods: A retrospective review was conducted that assessed patients undergoing elective surgery for incurable gastric carcinoma. Short- and long-term results were evaluated. Results: A total of 122 stage IV gastric cancer patients were assessed. Postoperative mortality was 5.7%, and the overall rate of complications was 35.2%. The overall survival rate at 1 and 3 years was 58 and 19% respectively; the median survival was 14 months. Improved survival was observed for the factors age less than 60 years (p = 0.015), site of metastases (p = 0.022), extended lymph node dissection (p = 0.044), absence of residual disease after surgery (p = 0.001), and administration of adjuvant chemotherapy (p = 0.016). Multivariate analysis showed that residual disease and adjuvant chemotherapy were independent prognostic factors. Conclusions: The results of this study suggest that surgery combined with systemic chemotherapy in selected patients with stage IV gastric cancer can improve survival.

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CDK5RAP3 as a Novel Biomarker Signature Predicting Survival and Adjuvant Chemotherapeutic benefit in Gastric Cancer

10.21203/rs.3.rs-130268/v1 ◽

2020 ◽

Author(s):

Jia-Bin Wang ◽

You-Xin Gao ◽

Ning-Zi Lian ◽

Yu-Bin Ma ◽

Ping Li ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Cox Model ◽

External Validation ◽

Tumour Tissue ◽

Tissue Samples ◽

Significant Difference ◽

Validation Set ◽

Gastric Cancer Patients

Abstract Background: We previously demonstrated that CDK5RAP3 acts as a tumour suppressor in gastric cancer through negative regulation of the Wnt/β-catenin signalling pathway, but its function in chemotherapeutic responsiveness of gastric cancer has not been investigated. In this study, we aimed to examine the clinical significance of CDK5RAP3 to predict chemotherapeutic responsiveness in gastric cancer.Methods: A collection of 188 pairs of tumour tissue microarray specimens from Fujian Medical University were employed for the discovery set, and 310 tumour tissue samples of gastric cancer patients were employed for the internal validation set. Eight-five tumour tissue samples from Qinghai University Hospital were used as the external validation set 1. Transcriptomic and clinical data of 299 gastric cancer patients from TCGA were used as the external validation set 2. CDK5RAP3 expression, microsatellite instability (MSI) status, and tumour-infiltrating lymphocytes (TIL) were examined with immunohistochemistry. Clinical outcomes of patients were compared with Kaplan-Meier curves and the Cox model.Results: In a multi-centre evaluation, increased CDK5RAP3 indication of better prognosis depends mainly on MSI-L/MSS status or TILhigh. High CDK5RAP3 expression predicts sensitive therapeutic responsiveness to postoperative adjuvant chemotherapy in gastric cancer. In a stratification analysis based on CDK5RAP3 combined with TIL or MSI status, patients with CKD5RAP3low TILlow showed no significant difference in prognosis after receiving chemotherapy, whereas patients with CKD5RAP3low TILhigh, CKD5RAP3high TILlow, and CKD5RAP3high TILhigh had better responsiveness to chemotherapy. In addition, patients with CKD5RAP3high MSI-L/MSS status benefitted the most from adjuvant chemotherapy among all patients evaluated. Conclusions: CKD5RAP3 can be used as an effective marker to evaluate individualized chemotherapy regimens in gastric cancer patients dependent on their TIL and MSI status.

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