Comprehensive Analysis of Potential Prognostic Values of ANGPTLs in Colorectal Cancer

Yang Zhang; Xuyang Yang; Sicheng Liu; Zixuan Zhuang; Mingtian Wei; Xiangbing Deng; Ziqiang Wang

doi:10.3390/genes13122215

journal article Open Access Nov 25, 2022

Comprehensive Analysis of Potential Prognostic Values of ANGPTLs in Colorectal Cancer

Yang Zhang

Xuyang Yang Sicheng Liu Zixuan Zhuang Mingtian Wei Xiangbing Deng Ziqiang Wang

Genes Vol. 13 No. 12 pp. 2215 · MDPI AG

View at Publisher Save 10.3390/genes13122215

Abstract

Colorectal cancer (CRC) is one of the most common malignant tumors in the world. CRC recurrence and metastasis cause poor prognosis. ANGPTLs (angiopoietin-like proteins) are a family of proteins that are widely involved in metabolic disease and tumorigenesis. The roles of ANGPTLs in CRC are still controversial and deserve further research. In this study, several databases were employed to explore the expression profiles, prognostic values, genetic alterations, potential biological function, and immune infiltration correlation of ANGPTLs in CRC. The expression of ANGPTL4 was significantly positively correlated with the stage of CRC. Therefore, cell and molecular experiments were further performed to explore the roles of ANGPTL4. Our results showed that the transcriptions of ANGPTLs in colon cancer and rectal cancer tissues were lower than those in normal tissues, but the protein expression varied among different ANGPTLs. In addition, the high expression of ANGPTLs led to a relatively poor oncological outcome. Specifically, the expression of ANGPTL4 is significantly positively correlated with the stage of CRC. Further investigation revealed that ANGPTLs are mainly involved in signal transduction and the regulation of transcription, while KEGG pathway analyses demonstrated pathways in cancer. Additionally, we also observed that ANGPTL4 could promote the proliferation and migration of CRC cells, and four specific small molecule compounds had potential ANGPTL4-binding capabilities, suggesting the clinical application of these small molecule compounds on CRC treatment. Our findings imply the prognostic values and potential therapeutic targets of ANGPTLs in CRC.

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References

59

[1]

Sung "Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries" CA Cancer J. Clin. (2021) 10.3322/caac.21660

[2]

Heald "Recurrence and survival after total mesorectal excision for rectal cancer" Lancet (1986) 10.1016/s0140-6736(86)91510-2

[3]

Cedermark "Improved survival with preoperative radiotherapy in resectable rectal cancer" N. Engl. J. Med. (1997) 10.1056/nejm199704033361402

[4]

Hohenberger "Standardized surgery for colonic cancer: Complete mesocolic excision and central ligation--technical notes and outcome" Color. Dis. (2009) 10.1111/j.1463-1318.2008.01735.x

[5]

Heald "The mesorectum in rectal cancer surgery—The clue to pelvic recurrence?" Br. J. Surg. (1982) 10.1002/bjs.1800691019

[6]

Wolpin "Adjuvant treatment of colorectal cancer" CA Cancer J. Clin. (2007) 10.3322/canjclin.57.3.168

[7]

Tol "Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer" N. Engl. J. Med. (2009) 10.1056/nejmoa0808268

[8]

Campbell "Survival following recurrence in stage II and III colon cancer: Findings from the ACCENT data set" J. Clin. Oncol. (2008) 10.1200/jco.2007.15.8261

[9]

Geiger "Metastasis mechanisms" Biochim. Et Biophys. Acta (2009)

[10]

Joyce "Microenvironmental regulation of metastasis" Nat. Rev. Cancer (2009) 10.1038/nrc2618

[11]

Oike "Angiopoietin-related/angiopoietin-like proteins regulate angiogenesis" Int. J. Hematol. (2004) 10.1532/ijh97.04034

[12]

Kim "Molecular cloning, expression, and characterization of angiopoietin-related protein. angiopoietin-related protein induces endothelial cell sprouting" J. Biol. Chem. (1999) 10.1074/jbc.274.37.26523

[13]

Bai "The Role of ANGPTL Gene Family Members in Hepatocellular Carcinoma" Dis. Mrk. (2022)

[14]

Tang "Mining the role of angiopoietin-like protein family in gastric cancer and seeking potential therapeutic targets by integrative bioinformatics analysis" Cancer Med. (2020) 10.1002/cam4.3100

[15]

Zajkowska, M., and Mroczko, B. (2021). Angiopoietin-like Proteins in Colorectal Cancer-A Literature Review. Int. J. Mol. Sci., 22. 10.3390/ijms22168439

[16]

Xiao "ANGPTL4 regulate glutamine metabolism and fatty acid oxidation in nonsmall cell lung cancer cells" J. Cell. Mol. Med. (2022) 10.1111/jcmm.16879

[17]

Morelli "Angiopoietin-like proteins as therapeutic targets for cardiovascular disease: Focus on lipid disorders" Expert Opin. Ther. Targets (2020) 10.1080/14728222.2020.1707806

[18]

Toiyama "Elevated serum angiopoietin-like protein 2 correlates with the metastatic properties of colorectal cancer: A serum biomarker for early diagnosis and recurrence" Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. (2014) 10.1158/1078-0432.ccr-14-0007

[19]

Soster "A complex of α6 integrin and E-cadherin drives liver metastasis of colorectal cancer cells through hepatic angiopoietin-like 6" EMBO Mol. Med. (2012) 10.1002/emmm.201101164

[20]

Chang "ANGPTL1 attenuates cancer migration, invasion, and stemness through regulating FOXO3a-mediated SOX2 expression in colorectal cancer" Clin. Sci. (2022) 10.1042/cs20220043

[21]

Jiang "Exosomal ANGPTL1 attenuates colorectal cancer liver metastasis by regulating Kupffer cell secretion pattern and impeding MMP9 induced vascular leakiness" J. Exp. Clin. Cancer Res. CR (2021) 10.1186/s13046-020-01816-3

[22]

Lim "Cd11b(+) myeloid cells support hepatic metastasis through down-regulation of angiopoietin-like 7 in cancer cells" Hepatology (2015) 10.1002/hep.27838

[23]

Kim "ANGPTL4 induction by prostaglandin E2 under hypoxic conditions promotes colorectal cancer progression" Cancer Res. (2011) 10.1158/0008-5472.can-11-1262

[24]

Shen "Oleic acid-induced NOX4 is dependent on ANGPTL4 expression to promote human colorectal cancer metastasis" Theranostics (2020) 10.7150/thno.44744

[25]

Huang "Mechanisms involved in biological behavior changes associated with Angptl4 expression in colon cancer cell lines" Oncol. Rep. (2012)

[26]

Nakayama "Expression of angiopoietin-like 4 (ANGPTL4) in human colorectal cancer: ANGPTL4 promotes venous invasion and distant metastasis" Oncol. Rep. (2011) 10.3892/or.2011.1176

[27]

Zhang "DNA methylation mediated down-regulation of ANGPTL4 promotes colorectal cancer metastasis by activating the ERK pathway" J. Cancer (2021) 10.7150/jca.52338

[28]

Santulli "Angiopoietin-like proteins: A comprehensive look" Front. Endocrinol. (2014) 10.3389/fendo.2014.00004

[29]

Tang "GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis" Nucleic Acids Res. (2019) 10.1093/nar/gkz430

[30]

Tissue-based map of the human proteome

Mathias Uhlén, Linn Fagerberg, Björn M. Hallström et al.

Science 2015 10.1126/science.1260419

[31]

Cerami "The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data" Cancer Discov. (2012) 10.1158/2159-8290.cd-12-0095

[32]

The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets

Damian Szklarczyk, Annika L Gable, Katerina C Nastou et al.

Nucleic Acids Research 2021 10.1093/nar/gkaa1074

[33]

Doncheva "Cytoscape StringApp: Network Analysis and Visualization of Proteomics Data" J. Proteome Res. (2019) 10.1021/acs.jproteome.8b00702

[34]

Sherman "DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update)" Nucleic Acids Res. (2022) 10.1093/nar/gkac194

[35]

Li "TIMER2.0 for analysis of tumor-infiltrating immune cells" Nucleic Acids Res. (2020) 10.1093/nar/gkaa407

[36]

Burley "RCSB Protein Data Bank: Powerful new tools for exploring 3D structures of biological macromolecules for basic and applied research and education in fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences" Nucleic Acids Res. (2021) 10.1093/nar/gkaa1038

[37]

Biterova "Structures of Angptl3 and Angptl4, modulators of triglyceride levels and coronary artery disease" Sci. Rep. (2018) 10.1038/s41598-018-25237-7

[38]

Diedrich "ProteinsPlus: Interactive analysis of protein-ligand binding interfaces" Nucleic Acids Res. (2020) 10.1093/nar/gkaa235

[39]

Analyzing the Topology of Active Sites: On the Prediction of Pockets and Subpockets

Andrea Volkamer, Axel Griewel, Thomas Grombacher et al.

Journal of Chemical Information and Modeling 2010 10.1021/ci100241y

[40]

Wei "Claudin-2 promotes colorectal cancer growth and metastasis by suppressing NDRG1 transcription" Clin. Transl. Med. (2021) 10.1002/ctm2.667

[41]

Meng, Y., Hu, X., Li, S., Zeng, X., Qiu, L., Wei, M., Wang, Z., and Han, J. (2020). miR-203 inhibits cell proliferation and ERK pathway in prostate cancer by targeting IRS-1. BMC Cancer, 20. 10.1186/s12885-020-07472-2

[42]

Mao "Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: New findings and future perspectives" Mol. Cancer (2021) 10.1186/s12943-021-01428-1

[43]

Benson "Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology" J. Natl. Compr. Cancer Netw. (2021) 10.6004/jnccn.2021.0012

[44]

Benson "NCCN Guidelines Insights: Rectal Cancer, Version 6.2020" J. Natl. Compr. Cancer Netw. (2020) 10.6004/jnccn.2020.0032

[45]

Hurwitz "Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer" N. Engl. J. Med. (2004) 10.1056/nejmoa032691

[46]

Saltz "Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: A randomized phase III study" J. Clin. Oncol. (2008) 10.1200/jco.2007.14.9930

[47]

Liu "Identification of Hub Genes Related to Liver Metastasis of Colorectal Cancer by Integrative Analysis" Front. Oncol. (2021) 10.3389/fonc.2021.714866

[48]

Fagiani "Angiopoietins in angiogenesis" Cancer Lett. (2013) 10.1016/j.canlet.2012.08.018

[49]

Zheng "Inhibitory receptors bind ANGPTLs and support blood stem cells and leukaemia development" Nature (2012) 10.1038/nature11095

[50]

Ito "Inhibition of angiogenesis and vascular leakiness by angiopoietin-related protein 4" Cancer Res. (2003)

Showing 50 of 59 references

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Published: Nov 25, 2022
Vol/Issue: 13(12)
Pages: 2215
License: View

Authors

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Yang Zhang