Prognostic significance of soluble forms of immune checkpoint PD-1/PDL1 receptor and ligand in blood plasma of gastric cancer patients

2021 ◽  
Vol 66 (3) ◽  
pp. 139-146
Author(s):  
Nikolay Evgenievich Kushlinskii ◽  
E. S. Gershtein ◽  
V. L. Chang ◽  
E. A. Korotkova ◽  
A. A. Alferov ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Blood Plasma ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Prognostic Significance ◽  
Specific Treatment ◽  
Long Term Treatment ◽  
Gastric Cancer Patients ◽  
In Blood Plasma

Analysis of long-term treatment results of 101 primary gastric cancer patients at various stages of the tumor process followed during 1 - 41 months (median - 6,4 months) from the onset of specific treatment are presented depending on the levels of soluble forms (s) of PD-1 receptor and its ligand PD-L1 in blood plasma. 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 (≥ 35 pg/ml) sPD-L1 levels in blood plasma, the overall survival of patients with gastric cancer was statistically significantly lower than at the marker’s levels below 35 pg / ml (p <0.045): 1-year survival comprised 78 and 96%, 2-year - 52 and 78%; 3-year - 40 and 61% at high and low sPD-L1 respectively. Median survival of patients with high plasma sPD-L1 comprised 29 months, of those with low sPD-L1 was not achieved during the whole follow-up period. This trend was observed not only in the total group of stage I-IV gastric cancer patients, but also in patients at the early stages of the disease, though sPD-L1 did not show an independent prognostic value in multiparametric model. At the same time, the overall survival of patients with gastric cancer did not depend on the baseline levels sPD-1 in blood plasma. Thus, soluble ligand sPD-L1 can be considered as a potentially valuable factor for prognosis of gastric cancer patients’ survival, and, probably, of anti-PD-1/PD-L1 treatment efficiency, but further studies and patients’ monitoring are required to prove this statement.

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.

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.

SOLUBLE FORMS OF PD-1 AND PD-L1 IN BLOOD PLASMA OF GASTRIC CANCER PATIENTS AND THEIR ASSOCIATIONS WITH CLINICAL AND MORPHOLOGICAL CHARACTERISTICS OF THE DISEASE

2020 ◽  
Vol 65 (6) ◽  
pp. 347-352 ◽  
Author(s):  
E. S. Gershtein ◽  
N. A. Ognerubov ◽  
V. L. Chang ◽  
V. V. Delektorskaya ◽  
E. A. Korotkova ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Blood Plasma ◽  
Cancer Patients ◽  
Cell Cancer ◽  
Morphological Characteristics ◽  
Control Group ◽  
Tnm System ◽  
Healthy Donors ◽  
Gastric Cancer Patients ◽  
In Blood Plasma

Results of comparative ELISA investigation of pretreatment sPD-1 and sPD-L1 content in blood plasma of 100 gastric cancer patients at various disease stages aged 25 to 81 years are presented. Control group included 60 practically healthy donors aged 18 - 68 years. Plasma sPD-L1 concentrations did not differ between gastric cancer patients and control group, and sPD-1 levels were statistically significantly lower in patients than in healthy donors (p<0.0001). Positive correlation (R=0.38; p=0.003) was revealed between plasma sPD-1 and sPD-L1 levels in control group and negative (R= -0.26; p=0,009) - in gastric cancer patients. ROC curve revealed the best sPD-1 cut-off level (< 21 pg/ml) with 77% sensitivity and 63.3% specificity, which is not sufficient for its application as diagnostic marker. Statistically significant increase of plasma sPD-L1 from stage I to stage IIIC (R=0.50; p=0.000011) was found. Analysis of associations between the evaluated markers’ levels and indices of gastric cancer expansion according to TNM system revealed statistically significant positive associations of plasma sPD-L1 levels with T (tumor invasion depth) and N (number of affected lymph nodes) indices: R=0.33; p=0.00093, and R=0.27; p=0.0099 respectively. sPD-L1 level was significantly increased in patients with low differentiated adenocarcinoma and cricoid-cell cancer as compared to highly differentiated adenocarcinoma (p=0.02 and p=0.004 respectively); in patients with cricoid-cell cancer it was also higher than in those with moderately differentiated adenocarcinoma (p=0.043) and undifferentiated cancer (p=0.049). Plasma sPD-1 level did not depend on disease stage, TNM system indices and tumor histological structure. Thus, soluble ligand sPD-L1, but not its receptor sPD-1, plasma level is increased in patients with unfavorable clinical and morphological characteristics, may be regarded as potentially valuable prognostic factor for gastric cancer patients’ survival, and probably as a predictor of anti - PD-1/PD-L1 treatment efficiency.

scholarly journals Clinicopathological and prognostic significance of metastasis-associated in colon cancer-1 in gastric cancer: A meta-analysis

2019 ◽  
Vol 34 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Yan Jin ◽  
Kun Zhou ◽  
Wenjing Zhao ◽  
Rongbo Han ◽  
Xinying Huo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Colon Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Clinicopathological Features ◽  
Poor Overall Survival ◽  
Expression Levels ◽  
Gastric Cancer Patients

Background: The gene metastasis-associated in colon cancer-1 (MACC1) has been reported to be overexpressed in diverse human malignancies, and an increasing amount of evidence suggests that its overexpression is associated with the development and progression of many human tumors. However, the prognostic and clinicopathological value of MACC1 in gastric cancer remains inconclusive. Therefore, we conducted this meta-analysis to investigate the effect of positive MACC1 expression on clinicopathological features and survival outcomes in gastric cancer. Methods: Medline, Web of Science, and EMBASE databases were searched for relevant articles published up to 10 April 2018. The correlation of MACC1 expression levels with overall survival and clinicopathological features was analyzed. Results: In this meta-analysis, nine studies with a total of 2103 gastric cancer patients were included. Our results showed that high expression of MACC1 was significantly related to a poor overall survival. Moreover, our meta-analysis showed that MACC1 overexpression was significantly linked to distant metastasis and vascular invasion. There were no significant correlations between positive MACC1 expression and gender, localization, tumor-node-metastasis (TNM) stage, tumor extent (T stage) and lymph node involvement (N stage) Conclusions: MACC1 expression levels can serve as a novel prognostic factor in gastric cancer patients.

scholarly journals Relationship between the Expression of the Thymidylate Synthase and the Prognosis of Gastric Cancer Patients Treated with Combinational Chemotherapy Regimen Including Fluorouracil, Docetaxel and Cisplatin

2020 ◽  
Author(s):  
Mozaffar Aznab ◽  
Seyed Majid Ahmadi ◽  
Sedigheh Khazaei ◽  
Sedigheh Khazaei ◽  
Seyed Mojtaba Ahmadi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Thymidylate Synthase ◽  
Prognostic Significance ◽  
Clinicopathologic Characteristics ◽  
Survival Status ◽  
Average Survival ◽  
Significant Difference ◽  
Gastric Cancer Patients

Background: Thymidylate synthase is one of the target enzymes of 5-fluorouracil. However, the clinical and prognostic significance of TS expression in gastric cancer has remained controversial. In this study, the expression of thymidylate synthase was evaluated in gastric cancer patients treated with combinational chemotherapy; moreover, the association between TS expression and clinicopathologic characteristics and overall survival of the patients were also assessed. Materials and Methods: In this descriptive study, 89 pathological samples were gathered from patients at Kermanshah hospitals during 2008-2017. The survival status of patients was recorded and their overall survival was evaluated individually. Results: The average survival period for low and high thymidylate synthase groups was 54 and 50 months, respectively, meaning higher survival time in the lower thymidylate group. But this difference was not statistically significant (log Rank=0.88). In addition, sex, stage, recurrence, and survival had no significant difference between the low and high expression of thymidylate synthase groups (p=0.89). Conclusion: The results clearly indicated that the level of thymidylate synthase is not a significant modulator of 5- fluorouracil in gastric cancer patients. Nevertheless, evaluation of the level of the enzymes and markers as well as their effects are highly recommended for accurate selection of chemotherapeutical strategies.

Prognostic value of epidermal growth factor receptors (EGFR) on overall survival of gastric cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14599-e14599 ◽  
Author(s):  
Alexandre A. A. Jácome ◽  
Durval R. Wohnrath ◽  
Cristovam Scapulatempo Neto ◽  
Estela C. Carneseca ◽  
Joao Soares Nunes ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Regression Model ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Membrane Expression ◽  
Egfr Family ◽  
Gastric Cancer Patients ◽  
Long Term Survivors

e14599 Background: The human EGFR family is involved in the pathogenesis and progression of several solid tumors. However, there is no consensus about the prognostic role of HER2 expression and of other members of EGFR family in gastric cancer patients. The aim of this study was to evaluate the prognostic value of members of the EGFR family in gastric cancer. Methods: Retrospective study with 201 patients with gastric and esophagogastric junction (EGJ) adenocarcinoma stages 0 to IV (AJCC 6th edition) who underwent primary tumor resection between January 2006 and December 2008 at Barretos Cancer Hospital, Barretos, São Paulo, Brazil. Tissue from primary tumors were analyzed by tissue microarray technology. IHC scores 0 and 1+ were classified as negative and scores 2+ and 3+ as positive, both for membrane and cytoplasmic expression of HER1, HER2, HER3 and HER4. The HER2 scoring system for gastric cancer was used for classification. Correlations between receptor expression and clinicopathological characteristics were performed according to the chi-square test. Survival analysis was calculated according to a parametric Weibull model with a mixture model incorporating long-term survivors. Multivariate analysis of prognostic factors was performed by a regression model incorporating long-term survivors with the Weibull distribution. Results: Membrane expression of HER1, HER2 and HER4 were 9%, 17% and 15%, respectively. No membrane expression of HER3 was observed. Cytoplasmic expression of HER1, HER3 and HER4 were 45%, 62% and 24%, respectively. Expression of HER2 and HER3 correlated with intestinal-type histology (p: 0.001 and p < 0.001, respectively) and advanced age (p: 0.011 and p: 0.008, respectively). According to a regression model adjusted for age, surgical radicality, surgical modality, Laurén histology, adjuvant therapy, TNM stage and receptors expressions, only TNM stage showed prognostic influence. Conclusions: Expression of HER2 and other members of EGFR family did not have influence on the overall survival in the gastric cancer population studied. The elaboration of a systematic review with meta-analysis or a prospective study could help elucidate this controversial issue.

scholarly journals Prognostic Role of the Circulating Tumor Cells Detected by Cytological Methods in Gastric Cancer: A Meta-Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Kun Zou ◽  
Shuailong Yang ◽  
Liang Zheng ◽  
Shuyi Wang ◽  
Bin Xiong
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
High Status ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Gastric Cancer Patients

Objective. We performed a meta-analysis of available studies to assess the prognostic value of circulating tumor cells detected by cytological methods for patients with gastric cancer. Methods. Two authors systematically searched the studies independently with key words in PubMed, MEDLINE, EMBASE, Science Citation Index Expanded, and Cochrane Library (from inception to April 2016). The estimated hazard ratio, risk ratio, odds ratio, and their 95% confidence intervals were set as effect measures. All analyses were performed by STATA 12.0. Results. Sixteen studies were included in this meta-analysis. CTCs-high status was significantly associated with poor overall survival (HR=2.23, 95% CI: 1.86–2.66) and progression-free survival (HR=2.02, 95% CI: 1.36–2.99). CTCs-high status was also associated with depth of infiltration (OR = 2.07, 95% CI: 1.16–3.70), regional lymph nodes metastasis (OR = 1.85, 95% CI: 1.26–2.71), and distant metastasis (OR = 2.83, 95% CI: 1.77–4.52). For unresectable gastric cancer patients, CTCs-high status was significantly associated with poor overall survival, progression-free survival, and disease control rate before and during chemotherapy group. Conclusions. Our meta-analysis has evidenced the significant prognostic value of CTCs detected for both PFS and OS in gastric cancer patients. For patients treated with chemotherapy alone, we proved that CTCs detected by cytological method showed a significant prognostic value and poor response to chemotherapy.

scholarly journals A preliminary evaluation of oxidative stress in patients with gastric cancer before chemotherapy

2021 ◽  
Author(s):  
Jarosław Jakubik ◽  
Joanna Kołodziejczyk-Czepas ◽  
Magdalena Kędzierska ◽  
Michał Kaczmarek ◽  
Paweł Nowak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gastric Cancer ◽  
Blood Plasma ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Control Group ◽  
Lipid Hydroperoxides ◽  
Thiol Groups ◽  
Gastric Cancer Patients ◽  
In Blood Plasma

IntroductionBackground: Due to an imbalanced redox status, cancer cells generate intrinsically higher levels of reactive oxygen species (ROS), compared to normal cells. Targeting ROS is an important therapeutic strategy for cancer as exemplified by cancer drugs, which induce ROS-dependent synergistic cytotoxicity in gastric cancer cells. The present study was designed to assess the level of selected oxidative stress biomarkers in blood plasma, derived from gastric cancer patients.Material and methodsThe study included the assessment of the oxidative/nitrative biomarkers in blood plasma isolated form 51gastric (adenocarcinoma) cancer patients, compared to a control group of 32 healthy volunteers. Oxidative stress was evaluated using a panel of biomarkers such as plasma protein thiol groups and 3-nitrotyrosine levels as well as indicators of plasma lipid peroxidation, i.e. lipid hydroperoxides (LOOH) and thiobarbituric acid-reactive substances (TBARS). Additionally, the total antioxidant capacity of blood plasma (non-enzymatic capacity of blood plasma, NEAC) was also estimated.ResultsOur results showed that patients with gastric cancer had changed levels of thiol groups (a decrease, p<0.001) and 3-nitrotyrosine (an increase, p<0.0001), LOOH (an increase, p<0.05), TBARS (an increase, p<0.05), NEAC (a decrease, p<0.0001), compared to the control group.ConclusionsThe presented study indicates on a considerable oxidative/nitrative stress in gastric cancer patients. Our pilot study shows that not a single marker, but a biomarkers panel may be a more reliable representation of oxidative stress in patients with gastric cancer.

Clinical significance and prognostic value of C-reactive protein/albumin ratio in gastric cancer

2020 ◽  
Author(s):  
Yan-jun Fu ◽  
Ke-zhi Li ◽  
Xin-qiang Liang ◽  
Zhi-qing Liang ◽  
Bai jihong
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Clinical Significance ◽  
Prognostic Value ◽  
Tnm Stage ◽  
C Reactive Protein ◽  
Albumin Ratio ◽  
Reactive Protein ◽  
Gastric Cancer Patients

Abstract Background C-reactive protein/albumin ratio (CAR) is a novel prognostic biomarker in several malignancies. This study was aimed to evaluate the clinical significance and prognostic value of CAR in patients with gastric cancer. Methods The data of 205 gastric cancer patients who underwent surgery was retrospectively reviewed. The association with the clinical features and prognostic value of CAR in gastric cancer was analyzed. The data of this study was combined with previous studies to further determine the prognostic value of CAR in patients with gastric cancer. Results Cox analysis revealed that preoperative CAR was an independent prognosis indicator in patients with gastric cancer. High expression of CAR indicated a shorter survival time than those with lower expression. CAR has a higher prognostic value in the 1-, 3-, 5-years of overall survival in patients with gastric cancer. However, CAR has no significant difference regarding the gastric cancer patients’ age, gender and TNM stage. The discriminated value of CAR in TNM stage of gastric cancer was moderate. A meta-analysis by combining previous data and our data showed that preoperative CAR was significantly associated with the overall survival of patients with gastric cancer. Conclusions This study demonstrated that preoperative CAR was an independent prognostic indicator in the patients with gastric cancer who underwent surgery.

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