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

Stavroula L Kastora, Georgios Kounidas, Valerie Speirs, Yazan A Masannat

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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.

Original languageEnglish
Article number3854
Number of pages18
Issue number16
Publication statusPublished - 9 Aug 2022

Bibliographical note

Funding: This research was funded by NHS Grampian Endowment Fund grant number NER11101
Acknowledgments: The authors would like to thank the NHS Grampian Breast Cancer Endowment Fund body for supporting the publication of the present manuscript and funding publication fees.

Data Availability Statement

Supplementary Materials: The following supporting information can be downloaded at, Figure S1: Identification of common proteins across BC secretome datasets: (A) tumors categorized as grade I and II and (B) tumors categorized as grade III. Figure S2: Blood levels of selected biomarkers (micrograms/Litre). DCIS to IDC progression biomarkers: TGFB1, DAG1, LGALS3BP, and LOXL2 (teal). IDC grade progression: HSPG2, ACTG1, and LAMA5 (plum). Pan-cancer biomarkers: ITGB1, FBN1, and THBS1 (cayenne). Table S1: Datasets included in the breast cancer secretome comparative analysis. Table S2: Datasets included in other cancer secretome comparative analysis. Table S3: Cell lines used in breast cancer and other malignancy integrative and comparative analysis. (accessed on 26 July 2022) Table S4: Human Protein Atlas prognosis and biological process of BC and comparative cancer patients for proteins identified in grade I and II BC vs. grade III BC clusters. Table S5. Blood levels of selected biomarkers. Table S6:
Abbreviation list.


  • IDC
  • bioinformatics
  • biomarkers
  • comparative analysis


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