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 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.

scholarly journals High Expression of Nucleobindin-2 Is Associated With Poor Prognosis in Gastric Cancer

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1021-A1021
Author(s):  
Junichi Okada ◽  
Eijiro Yamada ◽  
Tsugumichi Saito ◽  
Yasuyo Nakajima ◽  
Atsushi Ozawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Leucine Zipper ◽  
Independent Predictor ◽  
Clinical Stage ◽  
High Expression ◽  
Peripheral Tissues ◽  
Tumor Tissues ◽  
Gastric Cancer Patients ◽  
Cancer Tissues

Abstract Nucleobindin-2 (NUCB2) is a 396-amino acid protein, cleaved into the N-terminal nesfatin-11-82, nesfatin-285-163 and the C-terminal nesfatin-3166-396. NUCB2 contains a signal peptide, a leucine zipper structure, two Ca2+ binding EF-hand domains, and has a wide variety of basic cellular functions. NUCB2 is also a precursor protein of nesfatin-1, which was originally identified in hypothalamic nuclei, and which is a regulatory factor involved in the central control of food intake and energy balance. There are several reports indicating that NUCB2 is also expressed in various human peripheral tissues. Moreover, recent studies have reported that high levels of NUCB2 mRNA and protein are a potent prognostic factor for prostate cancer, endometrial carcinoma, and breast cancer. NUCB2 was also identified as a potential tumor antigen eliciting autoantibody responses in 5.4% of gastric cancer patients but not in the healthy individuals. However, theclinicopathological significance of NUCB2 expression in gastric cancer has still not been elucidated. Therefore, we examined NUCB2 expression in a large number of gastric cancer patients, using immunohistochemistry, to explore its clinicopathological significance. To explore this, we aimed to investigate the NUCB2 expression in gastric cancer tissues and adjacent non-tumor tissues and its potential relevance to clinicopathological factors and prognosis using immunohistochemistry analysis. In our study, NUCB2 level in gastric cancer tissues was higher than in non-tumor tissues. A high expression of NUCB2 is significantly associated with tumor depth, lymph node metastasis, lymphatic invasion, venous invasion and clinical stage. Furthermore, the expression level of NUCB2 protein was independent predictor of progression-free survival. In summary, NUCB2 might play a crucial role in gastric cancer development and could serve as an independent predictor of prognosis of gastric cancer patients.

scholarly journals TBL1XR1 Is Highly Expressed in Gastric Cancer and Predicts Poor Prognosis

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Fang Liu ◽  
Yuan He ◽  
Qinghua Cao ◽  
Ni Liu ◽  
Wenhui Zhang
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Cox Regression ◽  
Biological Significance ◽  
High Expression ◽  
Human Gastric Cancer ◽  
Mrna Levels ◽  
Poor Overall Survival ◽  
Cox Regression Analysis

Objective. To investigate the expression of transducin- (β-) like 1 X-linked receptor 1 (TBL1XR1) in human gastric cancer (GC) and its correlation with prognostic and biologic significance.Methods. TBL1XR1 mRNA expression was analyzed in gastric cancer using a microarray dataset (GSE2701) from the Gene Expression Omnibus (GEO). Immunohistochemistry (IHC) analysis of TBL1XR1 was performed on GC tissue microarray (TMA) to assess its prognostic and biological significance in 334 patients of GC.Results. Analysis of GSE2701 showed that the mRNA levels of TBL1XR1 were significantly elevated in primary gastric tumor and lymph node tissues than normal gastric tissues (P<0.05). The same results of TBL1XR1 protein level were observed by IHC staining in 334 GC tissues. 204 of 334 (60.1%) primary gastric cancer tissues showed high expression of TBL1XR1 protein. TBL1XR1 overexpression was significantly correlated with lymph node metastasis (P=0.000) and advanced TNM stage (P=0.001). Moreover, high levels of TBL1XR1 predicted worse overall survival (P=0.015). Multivariate Cox regression analysis indicated that high expression of TBL1XR1 was an independent prognostic factor for poor overall survival (HR, 0.525; 95% confidence interval, 0.367–0.752;P=0.005).Conclusion. This present study demonstrates that TBL1XR1 is overexpressed in gastric cancer and may be a potential predictor and therapeutic target for GC patients.

scholarly journals Up-regulation of DGAT1 in cancer tissues and tumor-infiltrating macrophages influenced survival of patients with gastric cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ping He ◽  
Shihuan Cheng ◽  
Feng Hu ◽  
Zhanchuan Ma ◽  
Yan Xia
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cell Line ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Potential Role ◽  
Gastric Cancer Treatment ◽  
Gastric Cancer Patients ◽  
And Function ◽  
Cancer Tissues

Abstract Background Diacylglycerol-acyltransferase 1 (DGAT1) plays an important role in the energy storage and is involved in cancer progression. A growing number of evidences showed that elevated expression of DGAT1 in cancer tissue indicated a poor outcome in cancer patients. However, the relationship between DGAT1 and gastric cancer is still unclear. Thus, Transcriptomic analysis and in vitro experiments were performed to investigate the role of DGAT1 in gastric cancer, as well as the potential therapy target in gastric cancer treatment. Methods We screened the public cancer datasets to identify the expression and function of DGAT1 in gastric cancer and tumor infiltrating lymphocytes. Then we testified the DGAT1 expression and function after sodium oleate treatment in AGS and MKN45 cell line. Finally, we analyzed ration of apoptosis, necrosis in gastric cancer cells by using flow cytometry after administration of DGAT1 inhibitor. Results Our results showed a highly expression of DGAT1 in gastric cancer tissues (n = 5, p = 0.0004), and tumor-infiltrating macrophages with elevated DGAT1 expression is associated with poor overall survival in gastric cancer patients. In addition, gastric cell lines AGS (n = 3, p < 0.05) and MKN45 (n = 3, p < 0.01) expressed higher level of DGAT1 than human gastric mucosal epithelial cell line GES-1. Administration of DGAT1 inhibitor effectively suppressed functional factors expression and induced cell death in MKN45. Conclusion The findings of this research provide an in-depth insight into the potential role and influences involved in DGAT1 in the gastric cancer patients. And higher expression of DGAT1 leads to lower overall survival (OS) rate in patients with poorly differentiated gastric cancer. Our findings suggest a potential role for DGAT1 in the gastric cancer progression and inhibiting DGAT1 might be a promising strategy in gastric cancer treatment.

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 Mannose Receptor as a Potential Biomarker for Gastric Cancer: A Pilot Study

2017 ◽  
Vol 32 (3) ◽  
pp. 278-283 ◽  
Author(s):  
Deng-Rui Liu ◽  
Quan-Lin Guan ◽  
Ming-Tai Gao ◽  
Lei Jiang ◽  
Hong-Xia Kang
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Mannose Receptor ◽  
Receptor Expression ◽  
High Expression ◽  
Cox Regression Analysis ◽  
Potential Biomarker ◽  
High Mannose ◽  
Gastric Cancer Patients

Background The mannose receptor is an immune adhesion molecule mainly expressed on the surface of antigen-presenting cells such as nonmature dendritic cells and macrophages. This study aimed to investigate mannose receptor expression and its predictive role in papillary gastric cancer patients. Methods The expression of the mannose receptor was measured in 120 samples of gastric cancer tissues and corresponding paracarcinoma tissues, by immunohistochemical and quantitative real-time PCR analysis. The relationships between mannose receptor expression and clinicopathological features of gastric cancer patients were analyzed. Results The expression rate of the mannose receptor in gastric cancer cells was 45.8% (54/120), significantly higher than that in the paracarcinoma tissue (20.0%, 36/120) (χ2 = 6.286, p = 0.012). High expression of the mannose receptor was closely related to tumor size, T stage, N stage and Union for International Cancer Control (UICC) stage of gastric cancer (p<0.05). A Kaplan-Meier survival model indicated that the survival of patients in the high-expression mannose receptor group was significantly shorter than in the low-expression mannose receptor group (p<0.05). Cox regression analysis showed that high mannose receptor expression was an independent predictor for the prognosis of patients with gastric cancer. Conclusions High mannose receptor expression indicates poor prognosis for gastric cancer patients. The mannose receptor may be an important molecular marker for gastric cancer prognosis.

scholarly journals Low Expression of PDHX is Associated with Poor Prognosis and Immune Infiltration in Gastric Cancer

2021 ◽  
Author(s):  
Biao Sun ◽  
Bao Li ◽  
Ziyang Long ◽  
Cangyuan Zhang ◽  
Qiannan Sun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Lymph Node ◽  
Survival Time ◽  
Cancer Patients ◽  
Distant Metastasis ◽  
Pyruvate Dehydrogenase ◽  
High Expression ◽  
Immune Infiltration ◽  
Gastric Cancer Patients ◽  
Cancer Tissues

Abstract Background: Pyruvate dehydrogenase protein X (PDHX) is a non-catalytic subunit of the pyruvate dehydrogenase (PDH) complex. It is located in the center of mitochondrial energy metabolism and is an essential component to maintain the biological activity of PDH complex. The purpose of this study was to explore its expression level in gastric cancer and its relationship with immune infiltration. Methods: Through immunohistochemical analysis of 80 pairs of gastric cancer tissue samples and open database analys such as Kaplan-Meier Plotter, TIMER2.0,GEPIA,String and DAVID database.Results: We found that the expression of PDHX in paracancerous tissues was significantly higher than that in gastric cancer tissues. Database analysis showed that the expression of PDHX was low in gastric cancer tissues, and the total survival time (OS) of relatively high expression in gastric cancer patients was higher. In N1~N3 and M stages, the P values of OS and PFS with high expression of PDHX were less than 0.05. It is suggested that the overexpression of PDHX may affect the prognosis of gastric cancer patients with lymph node and distant metastasis. Conclusions: Therefore, we concluded that the expression of PDHX is suppressed in gastric cancer and has a longer overall survival time of 5 years in patients with relatively high expression, and that the increased expression of PDHX may improve the prognosis of patients with lymph node and distant metastasis of gastric cancer.

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.

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.

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