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

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.

Download Full-text

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

10.21203/rs.3.rs-362393/v1 ◽

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.

Download Full-text

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

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.2089 ◽

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.

Download Full-text

Pretherapeutic circulating endostatin levels in patients with gastric cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.10095 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 10095-10095

Author(s):

S. H. Hong ◽

I. S. Woo ◽

H. M. Jeon ◽

S. Y. Rho ◽

S. J. Koh ◽

...

Keyword(s):

Gastric Cancer ◽

Survival Time ◽

Cancer Patients ◽

Distant Metastasis ◽

Distant Metastases ◽

Metastatic Gastric Cancer ◽

Lymph Node Status ◽

Healthy Controls ◽

Endostatin Level ◽

Gastric Cancer Patients

10095 Background: Endostatin is an antiangiogenic fragment of collagen XVIII and is generated by tumor-derived proteases. The functional activity of circulating endostatin is currently unknown. This is the first report on serum endostatin in gastric cancer. Methods: A total of 111 patients with gastric cancer (52 metastatic patients and 59 patients undergoing gastrectomy without distant metastasis) were included in the study. Forty eight of 52 (92%) metastatic patients received systemic chemotherapy. Pretherapeutic serum levels of endostatin and VEGF were measured using an ELISA and compared with the levels in 30 healthy controls. Data were analyzed using Student’s t-test and one-way ANOVA to compare means between groups, and using Spearman rank correlation to assess correlations between clinicopathologic factors and serum endostatin and VEGF levels. Survival curves were analyzed and compared using the Kaplan-Meier method and log-rank test. Results: Mean serum endostatin and VEGF levels were higher in gastric cancer patients than in healthy controls (endostatin, 69.8 ± 16.3 vs. 52.8 ± 6.0 ng/ml [P <0.001]; VEGF, 55.2 ± 7.5 vs. 31.9 ± 2.5 ng/ml [P <0.001]). Endostatin and VEGF levels were significantly higher in sera from metastatic patients than in sera from patients without distant metastasis (endostatin, 79.5 ± 17.9 vs. 61.3 ± 8.2 ng/ml [P <0.001]; VEGF, 57.4 ± 7.3 vs. 53.2 ± 7.2 ng/ml [P = 0.003]). There was a significant association between endostatin levels and the presence of distant metastases (r= 0.674; P <0.001). A correlation was also observed between serum endostatin and VEGF levels (r= 0.718; P <0.001). There was no significant difference in serum endostatin according to depth of tumor invasion, Lauren’s classification, differentiation, or regional lymph node status. A serum endostatin level higher than the median (78.14 ng/ml) was associated with a poor prognosis in metastatic gastric cancer (last follow- up at 42 months, median survival time 9 vs. 20 months [P=0.02]). Conclusions: In gastric cancer patients, serum endostatin levels are elevated and correlate with circulating VEGF levels as well as the presence of distant metastases. The endostatin level at diagnosis of metastatic gastric cancer may be useful for predicting survival time. No significant financial relationships to disclose.

Download Full-text