Integrative, In Silico and Comparative Analysis of Breast Cancer Secretome Highlights Invasive-Ductal-Carcinoma-Grade Progression Biomarkers

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 Aug 26

PMID 36010848

Authors

Stavroula L Kastora

Georgios Kounidas

Valerie Speirs

Yazan A Masannat

Affiliations

Soon will be listed here.

Abstract

Globally, BC is the most frequently diagnosed cancer in women. The aim of this study was to identify novel secreted biomarkers that may indicate progression to high-grade BC malignancies and therefore predict metastatic potential. A total of 33 studies of breast cancer and 78 of other malignancies were screened via a systematic review for eligibility, yielding 26 datasets, 8 breast cancer secretome datasets, and 18 of other cancers that were included in the comparative secretome analysis. Sequential bioinformatic analysis using online resources enabled the identification of enriched GO_terms, overlapping clusters, and pathway reconstruction. This study identified putative predictors of IDC grade progression and their association with breast cancer patient mortality outcomes, namely, HSPG2, ACTG1, and LAMA5 as biomarkers of in silico pathway prediction, offering a putative approach by which the abovementioned proteins may mediate their effects, enabling disease progression. This study also identified ITGB1, FBN1, and THBS1 as putative pan-cancer detection biomarkers. The present study highlights novel, putative secretome biomarkers that may provide insight into the tumor biology and could inform clinical decision making in the context of IDC management in a non-invasive manner.

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References

Yan G, Ding W, Xu S, Xu Z, Xiao C, Yin X . Characterization of phosphoproteins in gastric cancer secretome. OMICS. 2010; 15(1-2):83-90. DOI: 10.1089/omi.2010.0056. View

Cowan K, Storey K . Mitogen-activated protein kinases: new signaling pathways functioning in cellular responses to environmental stress. J Exp Biol. 2003; 206(Pt 7):1107-15. DOI: 10.1242/jeb.00220. View

Stuart-Harris R, Caldas C, Pinder S, Pharoah P . Proliferation markers and survival in early breast cancer: a systematic review and meta-analysis of 85 studies in 32,825 patients. Breast. 2008; 17(4):323-34. DOI: 10.1016/j.breast.2008.02.002. View

Yu H, Levesque M, Clark G, Diamandis E . Enhanced prediction of breast cancer prognosis by evaluating expression of p53 and prostate-specific antigen in combination. Br J Cancer. 1999; 81(3):490-5. PMC: 2362935. DOI: 10.1038/sj.bjc.6690720. View

Dudha N, Rana J, Rajasekharan S, Gabrani R, Gupta A, Chaudhary V . Host-pathogen interactome analysis of Chikungunya virus envelope proteins E1 and E2. Virus Genes. 2015; 50(2):200-9. DOI: 10.1007/s11262-014-1161-x. View

Zhang Q, Lu S, Li T, Yu L, Zhang Y, Zeng H . ACE2 inhibits breast cancer angiogenesis via suppressing the VEGFa/VEGFR2/ERK pathway. J Exp Clin Cancer Res. 2019; 38(1):173. PMC: 6482513. DOI: 10.1186/s13046-019-1156-5. View

Liu Y, Mi Y, Mueller T, Kreibich S, Williams E, van Drogen A . Multi-omic measurements of heterogeneity in HeLa cells across laboratories. Nat Biotechnol. 2019; 37(3):314-322. DOI: 10.1038/s41587-019-0037-y. View

Kalscheuer S, Khanna V, Kim H, Li S, Sachdev D, DeCarlo A . Discovery of HSPG2 (Perlecan) as a Therapeutic Target in Triple Negative Breast Cancer. Sci Rep. 2019; 9(1):12492. PMC: 6713791. DOI: 10.1038/s41598-019-48993-6. View

de Oliveira G, Paccielli Freire P, Cury S, de Moraes D, Oliveira J, Dal-Pai-Silva M . An Integrated Meta-Analysis of Secretome and Proteome Identify Potential Biomarkers of Pancreatic Ductal Adenocarcinoma. Cancers (Basel). 2020; 12(3). PMC: 7140071. DOI: 10.3390/cancers12030716. View

10.

Bartolini A, Cardaci S, Lamba S, Oddo D, Marchio C, Cassoni P . BCAM and LAMA5 Mediate the Recognition between Tumor Cells and the Endothelium in the Metastatic Spreading of KRAS-Mutant Colorectal Cancer. Clin Cancer Res. 2016; 22(19):4923-4933. DOI: 10.1158/1078-0432.CCR-15-2664. View

11.

Uhlen M, Fagerberg L, Hallstrom B, Lindskog C, Oksvold P, Mardinoglu A . Proteomics. Tissue-based map of the human proteome. Science. 2015; 347(6220):1260419. DOI: 10.1126/science.1260419. View

12.

Heimann R, Ferguson D, Hellman S . The relationship between nm23, angiogenesis, and the metastatic proclivity of node-negative breast cancer. Cancer Res. 1998; 58(13):2766-71. View

13.

Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A . ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009; 25(8):1091-3. PMC: 2666812. DOI: 10.1093/bioinformatics/btp101. View

14.

Tjalsma H, Antelmann H, Jongbloed J, Braun P, Darmon E, Dorenbos R . Proteomics of protein secretion by Bacillus subtilis: separating the "secrets" of the secretome. Microbiol Mol Biol Rev. 2004; 68(2):207-33. PMC: 419921. DOI: 10.1128/MMBR.68.2.207-233.2004. View

15.

Wang Z, Chen W, Zuo L, Xu M, Wu Y, Huang J . The Fibrillin-1/VEGFR2/STAT2 signaling axis promotes chemoresistance via modulating glycolysis and angiogenesis in ovarian cancer organoids and cells. Cancer Commun (Lond). 2022; 42(3):245-265. PMC: 8923131. DOI: 10.1002/cac2.12274. View

16.

Schaaij-Visser T, de Wit M, Lam S, Jimenez C . The cancer secretome, current status and opportunities in the lung, breast and colorectal cancer context. Biochim Biophys Acta. 2013; 1834(11):2242-58. DOI: 10.1016/j.bbapap.2013.01.029. View

17.

Zhang X, Ju S, Wang X, Cong H . Advances in liquid biopsy using circulating tumor cells and circulating cell-free tumor DNA for detection and monitoring of breast cancer. Clin Exp Med. 2019; 19(3):271-279. DOI: 10.1007/s10238-019-00563-w. View

18.

Ankney J, Xie L, Wrobel J, Wang L, Chen X . Novel secretome-to-transcriptome integrated or secreto-transcriptomic approach to reveal liquid biopsy biomarkers for predicting individualized prognosis of breast cancer patients. BMC Med Genomics. 2019; 12(1):78. PMC: 6543675. DOI: 10.1186/s12920-019-0530-7. View

19.

Weng T, Wang C, Hung Y, Chen W, Chen Y, Lai M . Differential Expression Pattern of THBS1 and THBS2 in Lung Cancer: Clinical Outcome and a Systematic-Analysis of Microarray Databases. PLoS One. 2016; 11(8):e0161007. PMC: 4981437. DOI: 10.1371/journal.pone.0161007. View

20.

Astudillo P, Larrain J . Wnt signaling and cell-matrix adhesion. Curr Mol Med. 2014; 14(2):209-20. DOI: 10.2174/1566524014666140128105352. View