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

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

10.21203/rs.3.rs-95106/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 ◽

External Validation ◽

University Hospital ◽

Tumour Tissue ◽

Tissue Samples ◽

Significant Difference ◽

Validation Set ◽

Gastric Cancer Patients

Abstract BackgroundWe 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. MethodA 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.ResultsIn 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. ConclusionsCKD5RAP3 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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Changes of weight and body composition after gastrectomy in the elderly gastric cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.89 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 89-89 ◽

Cited By ~ 1

Author(s):

Kenki Segami ◽

Toru Aoyama ◽

Yukio Maezawa ◽

Kazuki Kano ◽

Tsutomu Sato ◽

...

Keyword(s):

Gastric Cancer ◽

Body Composition ◽

Body Weight ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Lean Body Mass ◽

Body Mass ◽

The Elderly ◽

Significant Difference ◽

Gastric Cancer Patients

89 Background: Body weight, especially lean body mass, significantly reduces after gastrectomy for gastric cancer due to surgical invasion, reduced food intake, or decreased mobility, which could decrease quality of life and toxicity / compliance of adjuvant chemotherapy. These risks might be high especially in the elderly gastric cancer patients. However, it remains unclear whether changes of weight and body composition are different between the elderly and the non-elderly. Methods: This retrospective study examined patients who underwent curative surgery for gastric cancer between June 2010 and March 2014. Body weight and composition were evaluated by a bioelectrical impedance analyzer within 1 week before surgery (first measurement), at 1 week after surgery (second measurement), at 1 month after surgery (third measurement), and at 3 months after surgery (forth measurement). Patients were classified to the elderly (> 75 years) and the non-elderly ( < 75 years). Results: Four-hundred forty three patients (100 for the elderly and 343 for the non-elderly) were entered in the present study. Patients backgrounds, surgical factors, clinicopathological factors, surgical complications and adjuvant chemotherapy were not significantly different between the two groups. %Body weight loss until 1week, 1month, 3 months after surgery, defined as the proportion of the difference between 1st measurement and each measurement after surgery against 1st measurement, was 3.3%, 6.6%, and 9.7%, respectively in the elderly and 3.7%, 5.4%, and 8.2%, respectively in the non-elderly with significant difference (p = 0.05, 0.01, and 0.01, respectively). %Lean body mass loss until 1 week, 1 month, 3 months after surgery was 3.2%, 5.6%, and 6.1%, respectively in the elderly and 3.2%, 4.5%, and 4.2%, respectively in the non-elderly with p value of 0.36, 0.08, and 0.01, respectively. %Fat loss was not significantly different between the two groups at any time. Conclusions: Decreases in body weight and lean body mass after gastrectomy were more serious in the elderly patients as compared with the non-elderly. Surgical indication for the elderly must be carefully determined considering the risk and the benefit.

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Indications for adjuvant chemotherapy in patients with AJCC stage IIa T3N0M0 and T1N2M0 gastric cancer—an east and west multicenter study

BMC Gastroenterology ◽

10.1186/s12876-019-1096-8 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Ze-Ning Huang ◽

Jacopo Desiderio ◽

Qi-Yue Chen ◽

Chao-Hui Zheng ◽

Ping Li ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Multiple Regression ◽

Recursive Partitioning ◽

External Validation ◽

Seer Database ◽

Threshold Probability ◽

Significant Difference ◽

High Benefit ◽

Gastric Cancer Patients

Abstract Purpose To determine the indications for adjuvant chemotherapy (AC) in patients with stage IIa gastric cancer (T3N0M0 and T1N2M0) according to the 7th American Joint Committee on Cancer (AJCC). Methods A total of 1593 patients with T3N0M0 or T1N2M0 stage gastric cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database for the period 1988.1–2012.12. Cox multiple regression, nomogram and decision curve analyses were performed. External validation was performed using databases of the Fujian Medical University Union Hospital (FJUUH) (n = 241) and Italy IMIGASTRIC center (n = 45). Results Cox multiple regression analysis showed that the risk factors that affected OS in patients receiving AC were age > 65 years old, T1N2M0, LN dissection number ≤ 15, tumor size > 20 mm, and nonadenocarcinoma. A nomogram was constructed to predict 5-year OS, and the patients were divided into those predicted to receive a high benefit (points ≤ 188) or a low benefit from AC (points > 188) according to a recursive partitioning analysis. OS was significantly higher for the high-benefit patients in the SEER database and the FJUUH dataset than in the non-AC patients (Log-rank < 0.05), and there was no significant difference in OS between the low-benefit patients and non-AC patients in any of the three centers (Log-rank = 0.154, 0.470, and 0.434, respectively). The decision curve indicated that the best clinical effect can be obtained when the threshold probability is 0–92%. Conclusion Regarding the controversy over whether T3N0M0 and T1N2M0 gastric cancer patients should be treated with AC, this study presents a predictive model that provides concise and accurate indications. These data show that high-benefit patients should receive AC.

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Indications for adjuvant chemotherapy in patients with AJCC stage IIa T3N0M0 and T1N2M0 gastric cancer—an east and west multicenter study

10.21203/rs.2.11486/v3 ◽

2019 ◽

Author(s):

Ze-Ning Huang ◽

Jacopo Desiderio ◽

Qi-Yue Chen ◽

Chao-Hui Zheng ◽

Ping Li ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Multiple Regression ◽

Recursive Partitioning ◽

External Validation ◽

Seer Database ◽

Threshold Probability ◽

Significant Difference ◽

High Benefit ◽

Gastric Cancer Patients

Abstract Abstract Purpose To determine the indications for adjuvant chemotherapy (AC) in patients with stage IIa gastric cancer (T3N0M0 and T1N2M0) according to the 7 th American Joint Committee on Cancer (AJCC) Methods A total of 1593 patients with T3N0M0 or T1N2M0 stage gastric cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database for the period 1988.1-2012.12. Cox multiple regression, nomogram and decision curve analyses were performed. External validation was performed using databases of the Fujian Medical University Union Hospital (FJUUH) (n = 241) and Italy IMIGASTRIC center (n = 45). Results Cox multiple regression analysis showed that the risk factors that affected OS in patients receiving AC were age > 65 years old, T1N2M0, LN dissection number ≤ 15, tumor size > 20 mm, and nonadenocarcinoma. A nomogram was constructed to predict 5-year OS, and the patients were divided into those predicted to receive a high benefit (points ≤ 188) or a low benefit from AC (points > 188) according to a recursive partitioning analysis. OS was significantly higher for the high-benefit patients in the SEER database and the FJUUH dataset than in the non-AC patients (Log-rank < 0.05), and there was no significant difference in OS between the low-benefit patients and non-AC patients in any of the three centers (Log-rank = 0.154, 0.470, and 0.434, respectively). The decision curve indicated that the best clinical effect can be obtained when the threshold probability is 0-92%. Conclusion Regarding the controversy over whether T3N0M0 and T1N2M0 gastric cancer patients should be treated with AC, this study presents a predictive model that provides concise and accurate indications. These data show that high-benefit patients should receive AC.

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Indications for adjuvant chemotherapy in patients with AJCC (7th ed.) stage IIa T3N0M0 and T1N2M0 gastric cancer – an east and west, multicenter study

10.21203/rs.2.11486/v1 ◽

2019 ◽

Author(s):

Ze-Ning Huang ◽

Jacopo Desiderio ◽

Qi-Yue Chen ◽

Chao-Hui Zheng ◽

Ping Li ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Multiple Regression ◽

Recursive Partitioning ◽

Seer Database ◽

Threshold Probability ◽

Significant Difference ◽

High Benefit ◽

Gastric Cancer Patients

Abstract Purpose To determine the ideal indications of adjuvant chemotherapy(AC) in patients with stage IIa gastric cancer (T3N0M0 and T1N2M0) according to the 7th American Joint Committee on Cancer (AJCC) . Method 1593 gastric cancer patients with T3N0M0 or T1N2M0 stage were identified from Surveillance, Epidemiology,and End Results(SEER) database in 1988.1-2012.12. Cox multiple regression, nomogram and decision curve was used.External validation was performed using database from Fujian Medical University Union Hospital(FJUUH)(n = 241) and Italy IMIGASTRIC center(n = 45). Results Cox multiple regression analysis showed that the risk factors that affected OS in Patients with AC were age > 65 years old, T1N2M0, LN dissection number ≤ 15, tumor size > 20 mm, and non-adenocarcinoma. Then a nomogram was constructed to predict 5-year OS and divided patients into a high-benefit from AC (points ≤ 188) or a low-benefit (points > 188) according to a recursive partitioning analysis.OS was significantly higher for the high-benefit patients in the SEER database and the FJUUH dataset than in the non-AC patients (Log-rank < 0.05), and there was no significant difference in OS between low-benefit patients and non-AC patients among the three centers (Log-rank = 0.154, 0.470, and 0.434, respectively). The decision curve indicated that the best clinical effect can be obtained when the threshold probability is 0-92%. Conclusion Regarding the controversy over whether T3N0M0 and T1N2M0 gastric cancer patients should be treated with AC, this study presents a predictive model that provides concise and accurate indications. These data show that high-benefit patients should receive AC.

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Indications for adjuvant chemotherapy in patients with AJCC stage IIa T3N0M0 and T1N2M0 gastric cancer—an east and west multicenter study

10.21203/rs.2.11486/v2 ◽

2019 ◽

Author(s):

Ze-Ning Huang ◽

Jacopo Desiderio ◽

Qi-Yue Chen ◽

Chao-Hui Zheng ◽

Ping Li ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Multiple Regression ◽

Recursive Partitioning ◽

External Validation ◽

Seer Database ◽

Threshold Probability ◽

Significant Difference ◽

High Benefit ◽

Gastric Cancer Patients

Abstract Abstract Purpose To determine the indications for adjuvant chemotherapy (AC) in patients with stage IIa gastric cancer (T3N0M0 and T1N2M0) according to the 7th American Joint Committee on Cancer (AJCC) Methods A total of 1593 patients with T3N0M0 or T1N2M0 stage gastric cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database for the period 1988.1-2012.12. Cox multiple regression, nomogram and decision curve analyses were performed. External validation was performed using databases of the Fujian Medical University Union Hospital (FJUUH) (n = 241) and Italy IMIGASTRIC center (n = 45). Results Cox multiple regression analysis showed that the risk factors that affected OS in patients receiving AC were age > 65 years old, T1N2M0, LN dissection number ≤ 15, tumor size > 20 mm, and nonadenocarcinoma. A nomogram was constructed to predict 5-year OS, and the patients were divided into those predicted to receive a high benefit (points ≤ 188) or a low benefit from AC (points > 188) according to a recursive partitioning analysis. OS was significantly higher for the high-benefit patients in the SEER database and the FJUUH dataset than in the non-AC patients (Log-rank < 0.05), and there was no significant difference in OS between the low-benefit patients and non-AC patients in any of the three centers (Log-rank = 0.154, 0.470, and 0.434, respectively). The decision curve indicated that the best clinical effect can be obtained when the threshold probability is 0-92%. Conclusion Regarding the controversy over whether T3N0M0 and T1N2M0 gastric cancer patients should be treated with AC, this study presents a predictive model that provides concise and accurate indications. These data show that high-benefit patients should receive AC.

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CLINICAL SIGNIFICANCE OF SERUM CAVEOLIN-1 LEVELS IN GASTRIC CANCER PATIENTS

Experimental Oncology ◽

10.31768/2312-8852.2018.40(4):323-327 ◽

2018 ◽

Vol 40 (4) ◽

pp. 323-327 ◽

Cited By ~ 2

Author(s):

F Tas ◽

S Karabulut ◽

K Erturk ◽

D Duranyildiz

Keyword(s):

Gastric Cancer ◽

Cancer Patients ◽

Histological Grade ◽

Clinical Importance ◽

Disease Stage ◽

Control Group ◽

Tissue Samples ◽

Caveolin 1 ◽

Study Results ◽

Gastric Cancer Patients

Aim: Caveolin-1 plays a significant role in the pathogenesis of various carcinomas and its expression affects the survival of cancer patients. However, the molecular function of caveolin-1 and its possible clinical importance has remained uncertain in gastric cancer. No clinical trial has examined serum caveolin-1 levels in gastric cancer patients so far, instead all available results were provided from studies conducted on tissue samples. In the current study, we analyzed the soluble serum caveolin-1 levels in gastric cancer patients, and specified its associations with the clinical factors and prognosis. Material and Methods: Sixty-three patients with pathologically confirmed gastric cancer were enrolled into the trial. Serum caveolin-1 concentrations were detected by ELISA method. Thirty healthy subjects were also included in the study. Results: The median age of patients was 62 years, ranging from 28 to 82 years. The serum caveolin-1 levels in gastric cancer patients were significantly higher than those in control group (p < 0.001). The common clinical parameters including patient age, sex, lesion localization, histopathology, histological grade, disease stage, and various serum tumor markers (e.g. LDH, CEA, and CA 19.9) were not found to be associated with serum caveolin-1 levels (p > 0.05). Similarly, no correlation existed between serum caveolin-1 concentration and chemotherapy responsiveness (p = 0.93). Furthermore, serum caveolin-1 level was not found to have a prognostic role (p = 0.16). Conclusion: Even though it is neither predictive nor prognostic, serum caveolin-1 level may be a valuable diagnostic indicator in patients with gastric cancer. Key

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A PILOT STUDY OF HER-2/NEU GENE AMPLIFICATION ASSESSED BY FLUORESCENCE IN SITU HYBRIDIZATION (FISH) IN GASTRIC CANCER

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2014.3.2 ◽

2014 ◽

pp. 15-20

Author(s):

Van Huy Tran ◽

Thi Minh Thi Ha ◽

Trung Nghia Van ◽

Viet Nhan Nguyen ◽

Phan Tuong Quynh Le ◽

...

Keyword(s):

Gastric Cancer ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Cancer Patients ◽

Gene Amplification ◽

Cancer Tissue ◽

Tissue Samples ◽

Her 2 ◽

Gastric Cancer Patients

Background: HER-2/neu is a predictive biomarker for treatment of gastric cancer using trastuzumab in combination with chemotherapy. This study aimed to evaluate the status of HER-2/neu gene amplification using fluorescence in situ hybridization (FISH) in gastric cancer. Patients and methods: thirty six gastric cancer patients were assessed HER-2/neu gene amplification by FISH using PathVysionTM HER-2 DNA Probe kit (including HER-2/neu probe and CEP-17 probe) with biopsy and surgical specimens. Results: The HER-2/neu gene amplification was observed in three cases (8.3%), the HER-2/neu gene amplification rate in Lauren’s intestinal-type and diffuse-type were 11.8% and 5.2%, respectively. Conclusion: We applied successfully FISH technique with gastric cancer tissue samples. This technique could be performed as routine test in gastric cancer in order to select patients that benefit from trastuzumab in combination with chemotherapy.

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