Mining the role of angiopoietin‐like protein family in gastric cancer and seeking potential therapeutic targets by integrative bioinformatics analysis

Abstract Background The indistinctive effects of antiangiogenesis agents in gastric cancer (GC) can be attributed to multifaceted gene dysregulation associated with angiogenesis. Angiopoietin‐like (ANGPTL) proteins are secreted proteins regulating angiogenesis. They are also involved in inflammation...

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Main Authors: Cheng Tang, Erbao Chen, Ke Peng, Haiwei Wang, Xi Cheng, Yan Wang, Shan Yu, Yiyi Yu, Yuehong Cui, Tianshu Liu
Format: Article
Language:English
Published: Wiley 2020-07-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.3100
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author Cheng Tang
Erbao Chen
Ke Peng
Haiwei Wang
Xi Cheng
Yan Wang
Shan Yu
Yiyi Yu
Yuehong Cui
Tianshu Liu
author_facet Cheng Tang
Erbao Chen
Ke Peng
Haiwei Wang
Xi Cheng
Yan Wang
Shan Yu
Yiyi Yu
Yuehong Cui
Tianshu Liu
author_sort Cheng Tang
collection DOAJ
description Abstract Background The indistinctive effects of antiangiogenesis agents in gastric cancer (GC) can be attributed to multifaceted gene dysregulation associated with angiogenesis. Angiopoietin‐like (ANGPTL) proteins are secreted proteins regulating angiogenesis. They are also involved in inflammation and metabolism. Emerging evidences have revealed their various roles in carcinogenesis and metastasis development. However, the mRNA expression profiles, prognostic values, and biological functions of ANGPTL proteins in GC are still elucidated. Methods We compared the transcriptional expression levels of ANGPTL proteins between GC and normal gastric tissues using ONCOMINE and TCGA‐STAD. The prognostic values were evaluated by LinkedOmics and Kaplan–Meier Plotter, while the association of expression levels with clinicopathological features was generated through cBioPortal. We conducted the functional enrichment analysis with Metascape. Results The expression of ANGPTL1/3/6 was lower in GC tissues than in normal gastric tissues. High expression of ANGPTL1/2/4 was correlated with short overall survival and post‐progression survival in GC patients. Upregulated ANGPTL1/2 was correlated with higher histological grade, non‐intestinal Lauren classification, and advanced T stage, while ANGPTL4 exhibited high expression in early T stage, M1 stage, and non‐intestinal Lauren classification. Conclusions Integrative bioinformatics analysis suggests that ANGPTL1/2/4 may be potential therapeutic targets in GC patients. Among them, ANGPTL2 acts as a GC promoter, while ANGPTL1/4’s role in GC is still uncertain.
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spelling doaj-art-b7f2d22a5b4848d0afc18edb1567c29d2025-08-20T02:34:49ZengWileyCancer Medicine2045-76342020-07-019134850486310.1002/cam4.3100Mining the role of angiopoietin‐like protein family in gastric cancer and seeking potential therapeutic targets by integrative bioinformatics analysisCheng Tang0Erbao Chen1Ke Peng2Haiwei Wang3Xi Cheng4Yan Wang5Shan Yu6Yiyi Yu7Yuehong Cui8Tianshu Liu9Department of Medical Oncology Zhongshan Hospital Affiliated to Fudan University Shanghai PR ChinaDepartment of Medical Oncology Zhongshan Hospital Affiliated to Fudan University Shanghai PR ChinaDepartment of Medical Oncology Zhongshan Hospital Affiliated to Fudan University Shanghai PR ChinaDepartment of Medical Oncology Zhongshan Hospital Affiliated to Fudan University Shanghai PR ChinaDepartment of Medical Oncology Zhongshan Hospital Affiliated to Fudan University Shanghai PR ChinaDepartment of Medical Oncology Zhongshan Hospital Affiliated to Fudan University Shanghai PR ChinaDepartment of Medical Oncology Zhongshan Hospital Affiliated to Fudan University Shanghai PR ChinaDepartment of Medical Oncology Zhongshan Hospital Affiliated to Fudan University Shanghai PR ChinaDepartment of Medical Oncology Zhongshan Hospital Affiliated to Fudan University Shanghai PR ChinaDepartment of Medical Oncology Zhongshan Hospital Affiliated to Fudan University Shanghai PR ChinaAbstract Background The indistinctive effects of antiangiogenesis agents in gastric cancer (GC) can be attributed to multifaceted gene dysregulation associated with angiogenesis. Angiopoietin‐like (ANGPTL) proteins are secreted proteins regulating angiogenesis. They are also involved in inflammation and metabolism. Emerging evidences have revealed their various roles in carcinogenesis and metastasis development. However, the mRNA expression profiles, prognostic values, and biological functions of ANGPTL proteins in GC are still elucidated. Methods We compared the transcriptional expression levels of ANGPTL proteins between GC and normal gastric tissues using ONCOMINE and TCGA‐STAD. The prognostic values were evaluated by LinkedOmics and Kaplan–Meier Plotter, while the association of expression levels with clinicopathological features was generated through cBioPortal. We conducted the functional enrichment analysis with Metascape. Results The expression of ANGPTL1/3/6 was lower in GC tissues than in normal gastric tissues. High expression of ANGPTL1/2/4 was correlated with short overall survival and post‐progression survival in GC patients. Upregulated ANGPTL1/2 was correlated with higher histological grade, non‐intestinal Lauren classification, and advanced T stage, while ANGPTL4 exhibited high expression in early T stage, M1 stage, and non‐intestinal Lauren classification. Conclusions Integrative bioinformatics analysis suggests that ANGPTL1/2/4 may be potential therapeutic targets in GC patients. Among them, ANGPTL2 acts as a GC promoter, while ANGPTL1/4’s role in GC is still uncertain.https://doi.org/10.1002/cam4.3100angiopoietin‐like proteinsfunctional enrichmentgastric cancerprognostic valuetranscriptional expression level
spellingShingle Cheng Tang
Erbao Chen
Ke Peng
Haiwei Wang
Xi Cheng
Yan Wang
Shan Yu
Yiyi Yu
Yuehong Cui
Tianshu Liu
Mining the role of angiopoietin‐like protein family in gastric cancer and seeking potential therapeutic targets by integrative bioinformatics analysis
Cancer Medicine
angiopoietin‐like proteins
functional enrichment
gastric cancer
prognostic value
transcriptional expression level
title Mining the role of angiopoietin‐like protein family in gastric cancer and seeking potential therapeutic targets by integrative bioinformatics analysis
title_full Mining the role of angiopoietin‐like protein family in gastric cancer and seeking potential therapeutic targets by integrative bioinformatics analysis
title_fullStr Mining the role of angiopoietin‐like protein family in gastric cancer and seeking potential therapeutic targets by integrative bioinformatics analysis
title_full_unstemmed Mining the role of angiopoietin‐like protein family in gastric cancer and seeking potential therapeutic targets by integrative bioinformatics analysis
title_short Mining the role of angiopoietin‐like protein family in gastric cancer and seeking potential therapeutic targets by integrative bioinformatics analysis
title_sort mining the role of angiopoietin like protein family in gastric cancer and seeking potential therapeutic targets by integrative bioinformatics analysis
topic angiopoietin‐like proteins
functional enrichment
gastric cancer
prognostic value
transcriptional expression level
url https://doi.org/10.1002/cam4.3100
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