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

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.

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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

Almanac of Clinical Medicine ◽

10.18786/2072-0505-2018-46-4-323-329 ◽

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.

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Survival analysis of treatment with S-1, alone or in combination with CDDP (SP), in elderly patients with advanced gastric cancer: A 10-year retrospective cohort study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15170 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15170-e15170

Author(s):

Akitaka Makiyama ◽

Tatsuhiro Kajitani ◽

Hisanobu Oda ◽

Chinatsu Fujimoto ◽

Taito Esaki

Keyword(s):

Gastric Cancer ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Clinical Practice ◽

Advanced Gastric Cancer ◽

Cancer Patients ◽

Patient Characteristics ◽

The Elderly ◽

Metastatic Site ◽

Gastric Cancer Patients

e15170 Background: In Japan, the elderly population is increasing, and steadily increase the number of deaths in the elderly gastric cancer patients. However, the standard treatment of elderly gastric cancer has not been established, either treatment of S-1 or SP is carried out in the clinical practice, while SP is considered as standard therapy in the young people. Now, we investigated the impact of S-1 and SP on survival time in clinical practice. Methods: Between 2003 and 2012, advanced gastric cancer patients over 70 years of age received S-1 or SP as first line therapy were retrospectively reviewed to investigate clinical outcomes. Patient characteristics analyzed included age, gender, performance status (PS), tumor histology, renal function and metastatic site. In addition, we have analyzed prognostic factors in multivariate analysis. Results: Among 93 patients (pts), 67 pts (72%) received S-1 and 26 pts (28%) received SP. Patient characteristics between the two groups showed no significant differences in gender, histology, metastatic site, or creatinine clearance level, but did show an imbalance in PS (tended with better at SP group) and age (tended with younger at SP group), significantly. Even though the background factors were favorable results in SP group, there were no significant differences in median progression-free survival (median 139 vs. 102 days; p = 0.96) and overall survival (median 330 vs. 263 days; p = 0.55) between S-1 and SP group, respectively. Grade 3-4 neutropenia (10 vs. 27%, p < 0.05) , fatigue (3 vs. 15%, p < 0.05) and Grade 1-2 creatinine increased (9 vs. 31%, p < 0.01) were more frequent in the SP group than in the S-1 group, respectively. According to the multivariate analysis, exposure to CDDP was not independently associated with a better prognosis. Conclusions: Despite the obvious limitations of this analysis, there does not appear to be a benefit for the addition of CDDP in the elderly gastric cancer patients due to the increase of toxicity. A randomized controlled trial in this age group is warranted. We will also report the results of clinically meaningful prognostic factors associated with the primary treatment at annual meeting.

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