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Published on: May 17, 2019
Association of MMP-2 and hematological parameters with breast cancer metastasis: a cross-sectional study in Central
Alyssa Imani1, Yan Wisnu Prajoko2, Rudi Nirwantono1,3
1Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
Background:
Breast cancer metastasis remains a major contributor to morbidity and mortality, partly due to the disease's marked biological heterogeneity. Identification of reliable biomarkers associated with metastatic progression is essential for improving risk stratification and clinical management. Matrix metalloproteinase-2 (MMP-2) and routine hematological and metabolic parameters have been implicated in cancer progression, but their roles in breast cancer metastasis remain inconsistent across populations.
Methods:
This cross-sectional study evaluated general, hematological and metabolic parameters in breast cancer patients from Dr. Kariadi General Hospital, the main referral hospital for Central Java, Indonesia. Associations with metastasis were assessed using univariate analyses, followed by least absolute shrinkage and selection operator (LASSO) logistic regression for variable selection. Multicollinearity was assessed using variance inflation factor (VIF), and selected variables were entered simultaneously into a multivariable binary logistic regression model. Associations between selected hematological parameters and estrogen receptor (ER) and progesterone receptor (PR) status were also examined. Associations between clinicopathological variables and histologic grade were analyzed using the Kruskal-Wallis test.
Results:
Histologic grade was the only general characteristic significantly associated with metastasis (P < 0.001). In univariate analysis, metastatic patients showed significantly higher MMP-2, WBC count, and SGOT levels, whereas lower MCV and uric acid levels were detected. Multivariable logistic regression identified MMP-2 (P = 0.015; OR = 1.124, 95% CI: 1.023-1.236) and platelet count (P = 0.047; OR = 0.973, 95% CI: 0.947-1.000) as independently associated with breast cancer metastasis. Platelet count was also significantly associated with ER status (P = 0.039), but not with PR status (P = 0.054). Kruskal-Wallis analysis demonstrated significant differences in MMP-2 and uric acid levels across histologic grades I-III.
Conclusion:
Elevated MMP-2 levels and reduced platelets were independently associated with breast cancer metastasis, while platelets were additionally associated with ER status. These findings suggest that MMP-2 and platelet count may serve as potential biomarkers associated with metastatic behavior and hormone receptor status in breast cancer.