New drug developments in metastatic gastric cancer

Tan, Aaron C.; Chan, David; Faisal, Wasek; Pavlakis, Nick

doi:10.1177/1756284818808072

Cited by 20 publications

(13 citation statements)

References 95 publications

(104 reference statements)

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“…Over the last decades, great efforts have been made to provide novel understanding involving the early diagnosis, targeted therapy, and prognostic evaluation of GC 10,11. However, the overall survival time of GC patients remains unfavorable, particularly in some developing countries 12,13.…”

Section: Discussionmentioning

confidence: 99%

<p>A panel of collagen genes are associated with prognosis of patients with gastric cancer and regulated by microRNA-29c-3p: an integrated bioinformatics analysis and experimental validation</p>

Zhang¹,

Zhu²,

Xia³

et al. 2019

CMAR

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Background: The systematic expression characteristics and functions of collagen genes in gastric cancer (GC) have not been reported. Through public data integration, combined with bioinformatics analysis, we identified a panel of collagen genes overexpressed in GC. The functions of these genes were analyzed and validated in a GC-related cohort. microRNAs that may potentially target such genes were investigated in vitro. Methods: Four GC-related datasets retrieved from the Gene Expression Omnibus (GEO) were used to extract differentially expressed genes (DEGs) in GC. Functional annotation was performed to identify the potential roles of the identified DEGs. The association of candidate genes involved in the prognosis of GC patients (n=876) was determined using data provided by the Kaplan-Meier-plotter database, The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) repository, and a GC-related dataset (GSE15459). The expression characteristics of candidate genes and their associations with clinical parameters were validated in our in-house cohort (n=58). MicroRNAs able to target the identified candidate genes were predicted and confirmed using qRT-PCR, Western blotting, and dual-luciferase reporter assays in vitro. Results: After the integration of four GEO datasets, 76 DEGs were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that these DEGs were significantly enriched in ECM-related functions and pathways. A group of collagen genes was significantly upregulated in the GC tissues and constituted a proteinprotein interaction network as important nodes. Some of these collagen genes were closely associated with poor prognosis in GC patients. Overexpression of COL1A1 and COL4A1 was confirmed in our in-house cohort, and this was related to prognosis and certain clinicopathological parameters. We found that microRNA-29c-3p could directly target COL1A1 and COL4A1 in BGC-823 cells. Conclusions: Collagen genes identified in this study were associated with patient prognosis in GC and may represent diagnostic markers or potential therapeutic targets. Aberrant expression of such candidate genes may be induced by microRNA-29c-3p.

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Section: Discussionmentioning

confidence: 99%

<p>A panel of collagen genes are associated with prognosis of patients with gastric cancer and regulated by microRNA-29c-3p: an integrated bioinformatics analysis and experimental validation</p>

Zhang¹,

Zhu²,

Xia³

et al. 2019

CMAR

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“…Although a decreasing incidence of GC was observed in many countries due to the changes in eating habits and environment, GC remains prevalent in East Asia, especially in China, Japan and Korea [2]. Despite some advances in the diagnosis and treatment, the GC patients’ clinical outcome has not improved significantly at present [3]. In most countries, the 5-year overall survival rate for GC patients remains below 20% [4].…”

Section: Introductionmentioning

confidence: 99%

BCYRN1 is correlated with progression and prognosis in gastric cancer

Zhai

2019

Bioscience Reports

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Long non-coding RNA brain cytoplasmic RNA 1 (BCYRN1) has been found to play an important role in tumorigenesis of a variety of tumors including gastric cancer (GC). However, the prognostic significance and molecular mechanism of BCYRN1 was still unknown in GC. In the present study, we found BCYRN1 expression was dramatically elevated in GC tissues and cell lines, and positively associated with tumor depth, lymph node metastasis and clinical stage in patients with GC. Moreover, univariate and multivariate Cox regression analyses demonstrated that high BCYRN1 expression was independent prognostic factor for overall survival in GC patients. In lncRNA-microRNA interactome database, we found that there were putative binding sites between BCYRN1 and miR-204-5p. Furthermore, we confirmed that down-regulation of BCYRN1 inhibited GC cell proliferation, migration and invasion through directly up-regulated miR-204-5p expression. In conclusion, BCYRN1 acts as a promising prognostic predictor in GC patients and regulated GC cell proliferation, cell cycle, migration and invasion through targeting miR-204-5p.

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“…GC is a common upper gastrointestinal tumor type ( 27 ). Given the atypicality of clinical symptoms, numerous patients are already in the stage of advanced metastasis at the time of clear diagnosis and metastatic GC is closely related to poor prognosis ( 28 ). An effective treatment plan for GC is necessary.…”

Section: Discussionmentioning

confidence: 99%

“…At present, with the emergence of various biomarkers for GC, such as VEGFR2( 29 ), VEGF ( 30 , 31 ), EGFR ( 32 ), MET ( 33 ), PIK3CA ( 34 ) and mTOR ( 35 ), the corresponding targeted drugs have brought new hope regarding the OS of patients. Successful biomarkers require to be cost-effective and reproducible, but to date, challenges in identifying suitable predictive biomarkers have hampered the success of numerous targeted therapies for GC ( 28 ). Therefore, it is necessary to discover novel biomarkers that may accurately predict patient outcomes and allow for better treatment and follow-up decisions.…”

Section: Discussionmentioning

confidence: 99%

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High expression of PIG11 correlates with poor prognosis in gastric cancer

Zhang

et al. 2021

Exp Ther Med

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P53-induced gene 11 (PIG11) is an early transcription-related target of p53 that is involved in cell apoptosis and tumor development. However, its biological function in gastric cancer (GC) tissues and relationship with the prognosis of patients with GC have remained elusive. In the present retrospective study, 60 fresh and 790 paraffin-embedded samples of GC were obtained from the Affiliated Hospital of Nantong University (Nantong, China) with complete clinical data from all patients. Reverse transcription-quantitative PCR and tissue microarray-immunohistochemical analysis were used to determine the expression of PIG11 in the respective GC tissues. A receiver operating characteristic (ROC) curve was plotted to determine the diagnostic utility of PIG11 expression in GC. Furthermore, three online databases, including Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine and Kaplan-Meier plotter, were used for bioinformatics analysis of PIG11. PIG11 expression in GC tissues was high, which was positively correlated with invasive depth (P<0.001), lymph node metastasis (P<0.001), distant metastasis (P=0.019), TNM staging (P<0.001) and carcinoembryonic antigen in serum (P<0.001), and negatively associated with the overall survival of patients with GC. The ROC curve analysis suggested that based on PIG11 expression, it was possible to distinguish GC tissues from adjacent normal tissues (P<0.0001) with a sensitivity and specificity of 81.67 and 76.67%, respectively. In addition, Cox logistic regression analysis demonstrated that high PIG11 expression is a novel biomarker for unfavorable prognosis of patients with GC. Furthermore, the results obtained from the GEPIA database indicated that PIG11 expression is correlated with TNF, carcinoembryonic antigen related cell adhesion molecule 5, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha, VEGFA and kinase insert domain receptor. Therefore, PIG11 expression may be associated with the malignancy of GC and may serve as a potential diagnostic and prognostic biomarker for GC.

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New drug developments in metastatic gastric cancer

Cited by 20 publications

References 95 publications

<p>A panel of collagen genes are associated with prognosis of patients with gastric cancer and regulated by microRNA-29c-3p: an integrated bioinformatics analysis and experimental validation</p>

<p>A panel of collagen genes are associated with prognosis of patients with gastric cancer and regulated by microRNA-29c-3p: an integrated bioinformatics analysis and experimental validation</p>

BCYRN1 is correlated with progression and prognosis in gastric cancer

High expression of PIG11 correlates with poor prognosis in gastric cancer

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