scholarly journals ELISA study of matrix metalloproteinases 2, 7, 9 and their type 2 tissue inhibitor in the tumors of gastric cancer patients: clinical and pathologic correlations

2018 ◽  
Vol 46 (4) ◽  
pp. 323-329
Author(s):  
E. S. Gershtein ◽  
A. A. Ivannikov ◽  
V. L. Chang ◽  
N. A. Ognerubov ◽  
М. M. Davydov ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Matrix Metalloproteinases ◽  
Tumor Progression ◽  
Cancer Patients ◽  
Univariate Analysis ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Gastric Cancer Patients

Background: Over the last 10 years the incidence of gastric cancer has declined significantly. Nevertheless, it remains one of the most prevalent malignancies both in Russia and worldwide. Therefore, the problems of early diagnostics, prognosis and individualized treatment choice are still on the agenda. Much attention is paid to the evaluation of molecular biological characteristics of the tumor, as well as to the development of multiparametric prognostic systems for gastric cancer based on its identified characteristics. An important place among potential tumor biological markers belongs to matrix metalloproteinases (MMPs) involved into all the stages of tumor progression, first of all, into the regulation of invasion and metastasizing.Aim: Comparative quantitative evaluation of some MMP family members (MMP-2, 7, and 9) and one of the tissue MMP inhibitors (TIMP-2) levels in the tumors and adjacent histologically unchanged mucosa in gastric cancer patients, the analysis of their associations with the main clinical and pathological features of the disease and its prognosis.Materials and methods: Sixty six (66) primary gastric cancer patients (32 male and 34 female) aged 24 to 82 years (median, 61 year) were recruited into the study. Twenty two (22) patients were with stage I of the disease, 11 with stage II, 28 with stage III, and 5 with stage IV. The concentrations of the proteins studied were measured in the tumor and unchanged mucosa extracts by standard direct ELISA kits (Quantikine®, R&D Systems, USA).Results: Tumor MMP-2, 7 and 9 levels were significantly increased, compared to those in the adjacent histologically unchanged mucosa, in 80, 70 and 72% of gastric cancer patients, respectively, while the increase of TIMP-2 level found in 61% of the tumors was not statistically significant. Tumor MMP-2 and TIMP-2 content was increasing significantly with higher T index – size and advancement of the primary tumor (p < 0.01 and p < 0.05 respectively). Tumor MMP-2 level was also increasing in parallel with the N index (regional lymph node involvement; p < 0.01); it was significantly higher in the patients with distant metastases than in those without them (p < 0.05). Tumor MMP-9 and MMP-7 concentrations were not significantly associated with the indices of the tumor progression. The patients were followed up for 1 to 85 months (median, 18.3 months). According to the univariate analysis, high (> 32.6 ng/mg protein) MMP-2 and low MMP-7 (< 1.1 ng/mg protein) levels in the gastric cancer tissue represent statistically significant unfavorable prognostic factors for overall survival. Increased TIMP-2 level is associated with a non-significant decrease in the overall survival (p > 0.05), whereas the MMP-9 level was unrelated to the gastric cancer prognosis. Only T index (p = 0.0034) and tumor MMP-7 content (p = 0.026) remained independent prognostic factors in the multivariate regression analysis.Conclusion: The majority of gastric cancer patients demonstrate a significant increase in the expression of three MMP family members, i.e. gelatinases (MMP-2 and 9), and matrilysin (MMP-7), in the tumors, as compared to adjacent histologically unchanged mucosa. Only MMP-2 levels were associated with the disease progression, increasing with higher TNM system indices. High MMP-2 and low MMP-7 content in the gastric cancer tissue are significant unfavorable prognostic factors for the overall survival in the univariate analysis, but only MMP-7 has retained its independent prognostic value in the multivariate assessment.

The Clinicopathological Significance and Prognostic Value of Obg-Like Atpase 1 (OLA1) in Gastric Cancer

2021 ◽  
Author(s):  
Juan Wang ◽  
Zihan Zheng ◽  
Qinghua Cao ◽  
Xiufen Liu ◽  
Zhiqing Wang
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Biological Significance ◽  
High Expression ◽  
Cancer Tissue ◽  
Cox Regression Analysis ◽  
Gastric Cancer Patients ◽  
Cancer Tissues

Abstract Backgroud Obg-like ATPase 1 (OLA1) is a member of the Obg family of P-loop NTPases and has recently been detected in several human cancer cells. However, its expression type and clinical relevance in gastric cancer remains unclear. Methods In the present study, 2 datasets downloaded from the open Gene Expression Omnibus database were used to evaluate the mRNA level of OLA1 in gastric cancer. Quantitative Reverse Transcription PCR further validated the mRNA expression in gastric cancer tissues. Immunohistochemistry was performed on gastric cancer tissue microarray to assess OLA1 protein expression type, prognostic value, biological significance and its association with Snail in 334 patients of gastric cancer. The prognostic value of combination of OLA1 and Snail has been evaluated. Results The results showed that OLA1 mRNA and protein were elevated in gastric cancer tissues. High expression of OLA1 was significantly associated with aggressive features, such as tumor size, lymph node metastasis and TNM stage (P = 0.0146, P = 0.0037, P < 0.001, respectively). Moreover, high levels of OLA1 predicted worse overall survival. Multivariate Cox regression analysis indicated that high expression of OLA1 was an independent prognostic factor for poor overall survival (hazard ratio, 0.573; 95% confidence interval, 0.376–0.872; P = 0.009). Additionally, OLA1 expression was positively correlated with Snail, and combination of them revealed improved prognostic accuracy for gastric cancer patients. Conclusions Our results suggested that OLA1 high expression was considered as an independent factor for the prediction of unfavorable prognosis in gastric cancer patients, and we believe that OLA1 could serve as a biomarker of poor prognosis and a novel target in treating gastric cancers.

scholarly journals Prognostic Significance of Serum Uric Acid and Gamma-Glutamyltransferase in Patients with Advanced Gastric Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Shanshan Yang ◽  
Xinjia He ◽  
Ying Liu ◽  
Xiao Ding ◽  
Haiping Jiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Uric Acid ◽  
Prognostic Factors ◽  
Advanced Gastric Cancer ◽  
Cancer Patients ◽  
Serum Uric Acid ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Gamma Glutamyltransferase ◽  
Gastric Cancer Patients

Purpose. In this study, we aim to evaluate the prognostic role of serum uric acid and gamma-glutamyltransferase in advanced gastric cancer patients. Methods. A total of 180 patients pathologically diagnosed with advanced gastric cancer were included in this retrospective study. We used time-dependent receiver operating characteristic (ROC) curves to identify the optimal cut-off value of serum uric acid (UA) and gamma-glutamyltransferase (GGT). Survival analysis was performed using the Kaplan–Meier method and log-rank test, and multivariate Cox regression analyses were applied. A nomogram was formulated, and the calibration and discrimination of the nomogram were determined by calibration curve and concordance index (C-index). We validated the results using bootstrap resampling and a separate study on 60 patients collected from 2015 to 2017 using the same criteria in other medical center. Results. Both higher serum uric acid (>228 μmol/L) and higher gamma-glutamyltransferase (>14 U/L) had worse OS and PFS. Univariate analysis indicated that serum uric acid (UA) (p<0.001 and p<0.001) and gamma-glutamyltransferase (GGT) (p<0.001 and p=0.044) were significantly related to overall survival (OS) and progression-free survival (PFS), respectively. Multivariate analysis revealed serum uric acid (UA) and gamma-glutamyltransferase (GGT) were independent prognostic factors for OS (p=0.012, p=0.001). The optimal agreement between actual observation and nomogram prediction was shown by calibration curves. The C-indexes of the nomogram for predicting OS and PFS were 0.748 (95% CI: 0.70-0.79) and 0.728 (95% CI: 0.6741-0.7819), respectively. The results were confirmed in the validation cohort. Conclusion. We observed that both serum UA and GGT were poor prognostic factors in patients with advanced gastric cancer. And we also formulated and validated a nomogram which can predict individual survival for advanced gastric cancer patients.

Prognostic significance of VEGF signaling system components and matrix metalloproteinases in blood serum of gastric cancer patients

2021 ◽  
Vol 66 (11) ◽  
pp. 650-654
Author(s):  
Elena Sergeyevna Gershtein ◽  
E. A. Korotkova ◽  
A. P. Petrosyan ◽  
E. A. Suleymanov ◽  
I. S. Stilidi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Matrix Metalloproteinases ◽  
Blood Serum ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Vegf Signaling ◽  
Long Term Treatment ◽  
Gastric Cancer Patients ◽  
Vegf Level

Analysis of long-term treatment results of 77 primary gastric cancer patients at stage I-IV of the tumor process followed during 1 - 41 months (median - 6.4 months) from the onset of specific treatment are presented depending on the basal levels of VEGF, soluble forms of its receptors (sVEGFR1, sVEGFR2) and matrix metalloproteinases (MMP-2, 7, 9) in blood serum. Overall survival assessed by Kaplan-Meyer analysis and with the help of Cox multiparametric regression model was applied as the criterion of prognostic value. It was found that at high (≥ 420 pg/ml) serum VEGF, the overall survival of patients with gastric cancer was statistically significantly lower than at the marker’s levels below 420 pg/ml (p<0.011): 3-year’s survival comprised 46,3±12,5% and 88,2±7,8% respectively. Median survival of patients with high VEGF level comprised 21.7 months, of those with low VEGF was not achieved during the whole follow-up period. Serum sVEGFR1, sVEGFR2, MMP-2, 7 and 9 levels were not significantly associated with the overall survival of patients included in this study. Only index M of TNM system and serum VEGF level demonstrated an independent prognostic value in multiparametric model (p=0.036). Thus, it was confirmed that VEGF signaling pathway plays an important role in gastric cancer, and its components - in the first place, VEGF A - are substantial factors of disease prognosis, and can also be useful for monitoring of treatment efficiency.

scholarly journals Survival analysis of stage II gastric cancer patients after D2 gastrectomy: a Chinese people-based research

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zi-Jian Deng ◽  
Run-Cong Nie ◽  
Jun Lu ◽  
Xi-Jie Chen ◽  
Jun Xiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factors ◽  
Adjuvant Chemotherapy ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Cancer Patients ◽  
Univariate Analysis ◽  
Linitis Plastica ◽  
Stage Ii ◽  
Gastric Cancer Patients

Abstract Objective The benefit of adjuvant chemotherapy is still controversial for stage II gastric cancer patients. This study aims to identify prognostic factors to guide individualized treatment for stage II gastric cancer patients. Methods We retrospectively reviewed 1121 stage II gastric cancer patients who underwent D2 radical gastrectomy from 2007 to 2017 in the Sixth Affiliated Hospital of Sun Yat-sen University, FuJian Medical School Affiliated Union Hospital and Sun Yat-sen University Cancer Center. Propensity score matching was used to ensure that the baseline data were balanced between the adjuvant chemotherapy group and surgery-only group. Kaplan–Meier survival and multivariate Cox regression analyses were carried out to identify independent prognostic factors. Results In univariate analysis, after propensity score matching, age, tumor location, tumor size, CEA, T stage and N stage were associated with overall survival (OS). Multivariate analysis illustrated that age ≥ 60 years old, linitis plastica and T4 were independent risk factors for OS, but lower location and adjuvant chemotherapy were protective factors. Conclusion Stage II gastric cancer patients with adverse prognostic factors (age ≥ 60, linitis plastica and T4) have poor prognosis. Adjuvant chemotherapy may be more beneficial for these patients.

scholarly journals Norepinephrine Enhances Aerobic Glycolysis and May Act as a Predictive Factor for Immunotherapy in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yangyang Wang ◽  
Shuchang Wang ◽  
Qin Yang ◽  
Jun Li ◽  
Fengrong Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Normal Tissue ◽  
Aerobic Glycolysis ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Degrading Enzymes ◽  
Pet Ct ◽  
Gastric Cancer Patients ◽  
Low Expression

Objective/Background and Aims. The gastrointestinal tract is rich in neurotransmitters, which play an essential role in the occurrence and development of gastrointestinal tumors. We aimed to explore the function of neurotransmitters in gastric cancer and identify a suitable target to treat gastric cancer patients in the future. Methods. Monoamine neurotransmitters were detected in gastric cancer tissue and paired normal tissue, and The Cancer Genome Atlas was used to identify differentially expressed norepinephrine-degrading and synthetic enzymes. Quantitative real-time PCR and the Seahorse assay were used to determine the effect of norepinephrine on gastric cancer cell glycolysis. MAOA expression in cancer tissues was analyzed by immunohistochemistry and was compared with the patient SUVmax value of PET-CT and other clinicopathological characteristics. Results. The norepinephrine levels were markedly high in gastric cancer tissue, while the norepinephrine-degrading enzymes MAOA and MAOB showed low expression. High norepinephrine levels were associated with activated glycolysis. The MAOA or MAOB expression levels in tumor tissue were closely correlated with the patient SUV max values of PET-CT and immunotherapy evaluation indices, such as PD-L1 and the microsatellite status. Conclusions. Norepinephrine shows relatively higher expression in gastric cancer tissue than in normal tissue, and its expression level is associated with the glycolysis levels in patients. The norepinephrine-degrading enzymes MAOA and MAOB have significant expression differences in cancer and normal tissue, and their missing or low expression may predict immune therapy outcomes for gastric cancer patients. High norepinephrine levels with metabolic abnormalities may be more suitable for metabolic targeted therapy or immunotherapy.

scholarly journals Efficacy and Outcomes of Intraoperative Extensive Lavage Plus Surgery Versus Surgery Alone in Patients with Advanced Gastric Cancer: A Multicenter Randomized Controlled Trial

2021 ◽  
Author(s):  
Li-xiang Zhang ◽  
Chuan-hong Li ◽  
Jun Ma ◽  
Lei Chen ◽  
Zhi-jian Wei ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Advanced Gastric Cancer ◽  
Cancer Patients ◽  
Survival Curve ◽  
Recurrence Free Survival ◽  
Abdominal Abscess ◽  
Free Survival ◽  
Gastric Cancer Patients

Abstract Objective: This randomized study aims to evaluate the efficacy and long-term outcome of advanced gastric cancer patients with extensive intraoperative peritoneal lavage (EIPL). Methods: A total of 150 patients with advanced gastric cancer were enrolled in this study, the patients were randomly allocated to 2 groups: the group of surgery alone (non-EIPL group), the group of surgery plus EIPL (EIPL group). The surviving rate analysis was compared by the Kaplan–Meier method. The prognostic factors were carried out using the Cox appropriate hazard pattern. Results: Symptom of ileus and abdominal abscess appeared more frequently in the non-EIPL group(p<0.05). The overall survival (OS) curve and the recurrence free survival (RFS) curve of the EIPL group was better than the non-EIPL group (p<0.05). The EIPL, tumor size, vascular invasion, N stage and T stage were independent prognostic factors of overall survival. The independent risk factors of recurrence free survival (RFS) include EIPL and tumor size. Conclusions: The present study revealed that EIPL can reduce the possibility of perioperative complications including ileus and abdominal abscess. Besides, the overall survival curve and recurrence free survival curve are better in the EIPL group. This technique is easy and not-expensive, therefore EIPL can benefit advanced gastric cancer patients a lot and would be a promising therapeutic strategy in the future.Trial Registration: Clinical Trials.gov, identifier: NCT02745509, Registered 28 March2016,https://clinicaltrials.gov/ct2/show/NCT02745509?cond=NCT02745509&draw=2&rank=1.

CD40 signal expression in gastric cancer tissue and its correlation with prognosis of gastric cancer patients

2012 ◽  
Vol 39 (9) ◽  
pp. 8741-8747 ◽  
Author(s):  
Rui Li ◽  
Wei-Chang Chen ◽  
Xue-Qin Pang ◽  
Wen-Yan Tian ◽  
Wei-Peng Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Gastric Cancer Tissue ◽  
Cancer Tissue ◽  
Gastric Cancer Patients

scholarly journals Palliative Gastrectomy Prolongs Survival of Metastatic Gastric Cancer Patients with Normal Preoperative CEA or CA19-9 Values: A Retrospective Cohort Study

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Chang-Fang Chiu ◽  
Horng-Ren Yang ◽  
Mei-Due Yang ◽  
Long-Bin Jeng ◽  
Tse-Yen Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Cancer Patients ◽  
Performance Status ◽  
Metastatic Gastric Cancer ◽  
Palliative Gastrectomy ◽  
Cast Doubt ◽  
Gastric Cancer Patients ◽  
Univariate Analyses

Background. Palliative gastrectomy has been suggested to improve survival of patients with metastatic gastric cancer, but limitations in study design and availability of robust prognostic factors have cast doubt on the overall merit of this procedure. Methods. The characteristics and clinical outcomes of 173 patients diagnosed between 2008 and 2012 were analyzed to determine the value of palliative gastrectomy and to identify potential prognostic factors. Results. Median overall patient survival was 6.5 months. To attenuate potential selection bias, patients with adequate performance and survival time of ≥ 2 months since diagnosis were included for risk factor analysis (n=137). The median overall survival was longer for patients who were younger than 60 years, had better performance status (8.7 versus 6.4 months, P=0.015), received systemic chemotherapy, or had palliative gastrectomy in univariate analyses. Gastrectomy (P=0.002) remained statistically significant in multivariate analyses. Subgroup analysis showed that patients aged < 60 years, CEA < 5 ng/mL or CA19-9 < 35 U/mL, obtained a survival advantage from palliative gastrectomy. In fact, palliative gastrectomy doubled overall survival for patients who had normal CEA and/or normal CA19-9. Conclusions. Palliative gastrectomy prolongs the survival of metastatic gastric cancer patients with normal CEA and/or CA19-9 level at the time of diagnosis.

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