High expression of GNB4 predicts poor prognosis in patients with Helicobacter pylori-positive advanced gastric cancer

Background: Lysyl oxidase (LOX) is a key enzyme for the cross-linking of collagen and elastin in the extracellular matrix. This study evaluated the prognostic role of LOX in gastric cancer (GC) by analyzing the data of The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) dataset.Methods: The Wilcoxon rank-sum test was used to calculate the expression difference of LOX gene in gastric cancer and normal tissues. Western blot and immunohistochemical staining were used to evaluate the expression level of LOX protein in gastric cancer. Kaplan-Meier analysis was used to calculate the survival difference between the high expression group and the low expression group in gastric cancer. The relationship between statistical clinicopathological characteristics and LOX gene expression was analyzed by Wilcoxon or Kruskal-Wallis test and logistic regression. Univariate and multivariate Cox regression analysis was used to find independent risk factors affecting the prognosis of GC patients. Gene set enrichment analysis (GSEA) was used to screen the possible mechanisms of LOX and GC. The CIBERSORT calculation method was used to evaluate the distribution of tumor-infiltrating immune cell (TIC) abundance.Results: LOX is highly expressed in gastric cancer tissues and is significantly related to poor overall survival. Wilcoxon or Kruskal-Wallis test and Logistic regression analysis showed, LOX overexpression is significantly correlated with T-stage progression in gastric cancer. Multivariate Cox regression analysis on TCGA and GEO data found that LOX (all p < 0.05) is an independent factor for poor GC prognosis. GSEA showed that high LOX expression is related to ECM receptor interaction, cancer, Hedgehog, TGF-beta, JAK-STAT, MAPK, Wnt, and mTOR signaling pathways. The expression level of LOX affects the immune activity of the tumor microenvironment in gastric cancer.Conclusion: High expression of LOX is a potential molecular indicator for poor prognosis of gastric cancer.

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Improved survival by Helicobacter pylori-modulated immunity in gastric cancer patients with S-1 adjuvant chemotherapy

10.1101/2021.09.24.21263620 ◽

2021 ◽

Author(s):

Yuka Koizumi ◽

Sheny Ahmad ◽

Miyuki Ikeda ◽

Akiko Yashima-Abo ◽

Ginny Espina ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Advanced Gastric Cancer ◽

Cancer Patients ◽

Proportional Hazards ◽

Immune Escape ◽

Cox Proportional Hazards ◽

Prolonged Survival ◽

Host Immune System ◽

Gastric Cancer Patients

Background: Paradoxically, Helicobacter pylori-positive (HP+) advanced gastric cancer patients have a better prognosis than those who are HP-negative (HP-). Immunologic and statistical analyses can be used to verify whether systematic mechanisms modulated by HP are involved in this more favorable outcome. Methods: A total of 658 advanced gastric cancer patients who underwent gastrectomy were enrolled. HP infection, mismatch repair, programmed death-ligand 1 (PD-L1), and CD4/CD8 proteins, and microsatellite instability were analyzed. Overall survival (OS) and relapse free survival (RFS) rates were analyzed after stratifying clinicopathological factors. Cox proportional hazards regression analysis was performed to identify independent prognostic factors. Results: Among 491 cases that were analyzed, 175 (36%) and 316 (64%) cases were HP+ and HP⁻, respectively. Analysis of RFS indicated an interaction of HP status among the subgroups for S-1 Dose (P=0.0487) and PD-L1 (P=0.016). HP+ patients in the PD-L1- group had significantly higher five-year OS and RFS than HP- patients (81% vs. 68%; P=0.0011; HR 0.477; and 76% vs. 63%; P=0.0011; HR 0.508, respectively). The five-year OS and RFS was also significantly higher for HP⁺ compared to HP- patients in the PD-L1-/S-1-reduced group (86% vs. 46%; p=0.0014; HR 0.205; 83% vs. 34%; p=0.001; HR 0.190, respectively). Thus, HP status was identified as one of the most potentially important independent factors to predict prolonged survival. Conclusion: Modulation of host immune system function by HP may contribute to prolonged survival in the absence of immune escape mechanisms of gastric cancer.

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Prognostic value of biglycan in gastric cancer

10.21203/rs.3.rs-103093/v1 ◽

2020 ◽

Author(s):

Sizhe Hu ◽

Peipei Li ◽

Chenying Wang ◽

Xiyong Liu

Keyword(s):

Gastric Cancer ◽

Transcription Factors ◽

Poor Prognosis ◽

Prognostic Significance ◽

Bioinformatic Analysis ◽

Gene Set Enrichment Analysis ◽

High Expression ◽

Mrna Levels ◽

Gene Signatures ◽

Kaplan Meier

Abstract Background: BGN (biglycan) is a family member of small leucine-rich repeat proteoglycans. High expression of BGN might enhance the invasion and metastasis in some types of tumors. Here, the prognostic significance of BGN was evaluated in gastric cancer.Material and Methods: Two independent Gene Expression Omnibus (GEO) gastric cancer microarray datasets( n= 64, n=432) were collected for this study. Kaplan-Meier analysis was applied to evaluate if BGN impacts the outcomes of gastric cancer. The gene set enrichment analysis (GSEA) was used to explore BGN and cancer-related gene signatures. Bioinformatic analysis predicted the putative transcription factors of BGN.Results: For gastric cancer, the mRNA expression level of BGN in tumor tissues was significantly higher than that in normal tissues. Kaplan-Meier analysis showed that higher expression of BGN mRNA was significantly associated with more reduced recurrence-free survival (RFS). GSEA results suggested that BGN significantly enriched metastasis and poor prognosis gene signatures, revealing that BGN might be associated with cell proliferation, poor differentiation, high invasiveness of gastric cancer. Meanwhile, the putative transcription factors, including AR, E2F1, and TCF4, weres predicted by bioinformatic analysis and also significantly correlated with expression of BGN in mRNA levels. Conclusion: High expression of BGN mRNA was significantly related to poor prognosis, which suggested BGN was a potential prognostic biomarker and therapeutic target of gastric cancer.

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The Aberrant Expression of MicroRNA-125a-5p/IGF2BP3 Axis in Advanced Gastric Cancer and Its Clinical Relevance

Technology in Cancer Research & Treatment ◽

10.1177/1533033820917332 ◽

2020 ◽

Vol 19 ◽

pp. 153303382091733

Author(s):

Jing Zhang ◽

Fanghui Ding ◽

Dan Jiao ◽

Qiaozhi Li ◽

Hong Ma

Keyword(s):

Gastric Cancer ◽

Growth Factor ◽

Advanced Gastric Cancer ◽

Messenger Rna ◽

Poor Prognosis ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Advanced Stage ◽

Insulin Like Growth Factor

RNA-binding proteins have been associated with cancer development. The overexpression of a well-known RNA-binding protein, insulin-like growth factor 2 messenger RNA–binding protein 3, has been identified as an indicator of poor prognosis in patients with various types of cancer. Although gastric cancer is a relatively frequent and potentially fatal malignancy, the mechanism by which insulin-like growth factor 2 messenger RNA–binding protein 3 regulates the development of this cancer remains unclear. This study aimed to investigate the role and regulatory mechanism of insulin-like growth factor 2 messenger RNA–binding protein 3 in gastric cancer. An analysis of IGF2BP3 expression patterns reported in 4 public gastric cancer–related microarray data sets from the Gene Expression Omnibus and The Cancer Genome Atlas-Stomach Adenocarcinoma revealed strong expression of this gene in gastric cancer tissues. Insulin-like growth factor 2 messenger RNA–binding protein 3 expression in gastric cancer was further confirmed via quantitative reverse transcription polymerase chain reaction and immunohistochemistry, respectively, in an in-house gastric cancer cohort (n = 30), and the association of insulin-like growth factor 2 messenger RNA–binding protein 3 expression with clinical parameters and prognosis was analyzed. Notably, stronger IGF2BP3 expression significantly correlated with poor prognosis, and significant changes in insulin-like growth factor 2 messenger RNA–binding protein 3 expression were only confirmed in patients with advanced-stage gastric cancer in an independent cohort. The effects of insulin-like growth factor 2 messenger RNA–binding protein 3 on cell proliferation were confirmed through in vitro experiments involving the HGC-27 gastric cancer cell line. MicroR-125a-5p, a candidate microRNA that target on insulin-like growth factor 2 messenger RNA–binding protein 3, decreased in advanced-stage gastric cancer. Upregulation of microR-125a-5p inhibited insulin-like growth factor 2 messenger RNA–binding protein 3, and dual-luciferase report assay indicated that microR-125a-5p inhibited the translation of IGF2BP3 by directly targeting the 3′ untranslated region. These results indicate that the microR-125a-5p/insulin-like growth factor 2 messenger RNA–binding protein 3 axis contributes to the oncogenesis of advanced gastric cancer.

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FARP1 boosts CDC42 activity from integrin αvβ5 signaling and correlates with poor prognosis of advanced gastric cancer

Oncogenesis ◽

10.1038/s41389-020-0190-7 ◽

2020 ◽

Vol 9 (2) ◽

Author(s):

Takuro Hirano ◽

Yoshinari Shinsato ◽

Kan Tanabe ◽

Nayuta Higa ◽

Muhammad Kamil ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Poor Prognosis

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Hyperprogressive disease during nivolumab or irinotecan treatment in patients with advanced gastric cancer

ESMO Open ◽

10.1136/esmoopen-2019-000488 ◽

2019 ◽

Vol 4 (3) ◽

pp. e000488 ◽

Cited By ~ 11

Author(s):

Masahiko Aoki ◽

Hirokazu Shoji ◽

Kengo Nagashima ◽

Hiroshi Imazeki ◽

Takahiro Miyamoto ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Advanced Gastric Cancer ◽

Survival Benefit ◽

Poor Prognosis ◽

Tumour Growth ◽

Progression Free Survival ◽

Free Survival ◽

Prior Therapy ◽

Hyperprogressive Disease

BackgroundNivolumab showed a survival benefit for advanced gastric cancer (AGC). However, an acceleration of tumour growth during immunotherapy, (hyperprogressive disease, HPD) has been reported in various cancers. This study reviewed the HPD in patients with AGC treated with nivolumab or irinotecan.MethodsThe subjects of this retrospective study were patients with AGC with measurable lesions, and their tumour growth rates (TGR) during nivolumab or irinotecan were compared with those during prior therapy. HPD was defined as an increase in TGR more than twofold.Results34 and 66 patients received nivolumab and irinotecan in third or later line between June 2009 and September 2018 at our hospital; 22 patients receiving nivolumab had prior treatment with irinotecan, and one patient received irinotecan after nivolumab. Nivolumab and irinotecan showed no differences in disease control rates (38.2% and 34.8%) and in progression-free survival (PFS) (HR 1.1, 95% CI 0.7 to 1.6, p=0.802). The incidence of HPD was slightly higher after nivolumab (29.4%) than after irinotecan (13.5%) (p=0.0656), showing no differences in background between the patients with and without HPD. Compared between HPD and PD other than HPD after nivolumab, the HRs for PFS and overall survival (OS) were 1.1 (95% CI 0.5 to 2.7; p=0.756), and 2.1 (95% CI 0.7 to 5.8; p=0.168), but such clear difference in OS was not observed after irinotecan.ConclusionsHPD was observed more frequently after nivolumab compared with irinotecan, which was associated with a poor prognosis after nivolumab but not so clearly after irinotecan.

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