Abstract 3789: Discovery of liquid biopsy-based novel protein biomarkers for early detection of breast cancer metastasis

Abstract

Abstract Introduction and Objectives: Despite recent advances in screening and therapeutic technology, breast cancer is still the first leading cause of cancer death among females. When detected early (i.e., SEER Stage Localized), the 5-yr survival rate is 99%. The 5-yr survival rate is still 86% when cancer cells have spread beyond the breast, but this spread is limited to nearby lymph nodes (SEER Stage Regional). However, when the disease is noted to be SEER Stage Distant or metastasis, the 5-yr survival rate is significantly reduced to 31%. The evidence suggests that breast cancer is manageable if distant metastasis could be prevented. Thus, the prevailing idea is that early detection of breast cancer metastasis in surveillance will likely be the best modality to address advanced breast cancer’s dismal outcomes. Thus, liquid biopsy may be suitable for “early detection” of pre- and/or micro-metastasis because of its ease of obtaining biological material. In this pilot study, we explored the potential biomarkers for the early detection of breast cancer metastasis using publicly available datasets. Methods: We obtained 2 publicly available datasets from GEO (GSE102484 and GSE234114) containing primary tumor samples taken from subjects with and without metastatic disease. Both datasets were generated by mRNA microarray (Affymetrix Human Genome U133 Plus 2.0 Array). With these datasets, we performed the differentially expressed gene (DEG) analysis using GEO2R based on GEOquery and limma (Linear Models for Microarray Analysis) with a threshold criterion of Log 2 fold change >0 and p-value <0.05 as the cut-off point. The significantly upregulated genes were further screened using VerSeDa (Vertebrate Secretome Database) to select secreted proteins. Results: In the GSE102484 (N = 683, 582 non-metastasis and 101 metastasis), DEG identified 1798 upregulated and 1472 downregulated genes. Venn diagram analysis between the upregulated genes and VerSeDa identified 337 upregulated genes coding secreted proteins. In the GSE234114 (N = 120, 60 non-metastasis and 60 metastasis), DEG identified 2873 upregulated and 931 downregulated genes. Venn diagram analysis between the upregulated genes and VerSeDa identified 563 upregulated genes coding secreted proteins. By integrating the genes from GSE102484 and GSE234114, 82 commonly upregulated genes that code secreted proteins were identified. Conclusions: In this study, we identified 82 candidate mRNA biomarkers that are upregulated in breast tumor with metastasis. The panel of biomarkers will be validated in blood-based liquid biopsy samples in the next study. Citation Format: Cynthia Jinno, Sunao Tanaka, Takeo Fujii, Hideki Furuya. Discovery of liquid biopsy-based novel protein biomarkers for early detection of breast cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3789.