Baqer A. Altimmime, Farah A. Rashid, Yaala Saady Raof, Omran Mansour

CXCL12, CA15-3, and Liver function Tests as Predictors of Liver Metastasis in Breast Cancer

Introduction

Cxcl12, ca15-3, and liver function tests as predictors of liver metastasis in breast cancer. Discover which markers predict breast cancer liver metastasis. This study assesses CXCL12, CA15-3, and liver function tests, finding ALP, AST, and albumin are better predictors.

Abstract

Breast cancer liver metastasis (BCLM) is a multi- step process that characterized by the spread of breast cancer cells to the liver. The majority of breast cancer-related deaths are due to metastatic rather than primary breast tumors. CXCL12 is one of the chemokines, small proteins capable of migrating various types of immune cells to the site of inflammation. CXCL12 can affect several cell biological activities, such as migration and proliferation, when it binds to its receptors. The aim of this study is to investigate the predictive value of plasma CXCL12, CA15-3, and some liver-related parameter levels in breast cancer patients with liver metastasis. This study involves 94 women, 25 healthy controls and 69 patients with breast cancer, divided into three subgroups: 26 newly diagnosed women with primary breast cancer, 28 women with non-metastatic breast cancer undergoing chemotherapy, and 15 women with liver metastatic breast cancer. Plasma levels of CXCL12, CA15-3, albumin, ALP, ALT, and AST were measured using absorbance photometry and ELISA assays. The results of the study reveals that the level distributions of CXCL12 (p‎>0.9999) and CA15-3 (p‎>0.9999) showed no significant difference between breast cancer patients with and without liver metastasis. Albumin levels were significantly lower (‎‎p=0.0089) in women with liver metastatic breast cancer compared to those without metastasis. Levels of ALP‎ (p=‎0.0006‎), ALT (‎p=0.0015), and AST (p‎‎<0.0001) were significantly elevated in breast cancer liver metastatic patients compared to patients without metastasis. CXCL12 ‎(AUC, ‎0.5840‎, p=‎0.3788‎)‎ and CA15-3 ‎(AUC, ‎0.5787‎, p=‎0.4099‎)‎ could not serve as reliable discriminatory parameters for liver metastasis. Albumin ‎(AUC, ‎0.7267‎, p=‎0.0176‎) showed a moderate ability to distinguish between BC patients with and without BCLM‎. ALP (AUC, 0.8693, p=0.0001) and AST (AUC, 0.9453, p<0.0001) exhibited the highest diagnostic accuracies for liver metastasis. Together, none of the study parameters was identified as an independent risk factor for liver metastasis in breast cancer patients.

Review

This study addresses the critical clinical challenge of breast cancer liver metastasis (BCLM), a major cause of mortality in breast cancer patients. The authors aimed to evaluate the predictive utility of plasma CXCL12, CA15-3, and several liver function test parameters (albumin, ALP, ALT, AST) in identifying BCLM. Given the importance of early and accurate detection of metastasis for guiding treatment strategies, investigating novel and established biomarkers, alongside routine clinical tests, is a highly relevant endeavor in oncology. The rationale for including CXCL12 as a chemokine involved in cell migration and proliferation, alongside the established tumor marker CA15-3 and standard liver health indicators, provides a comprehensive approach to biomarker assessment for BCLM. The study employed a cross-sectional design involving 94 women, categorized into healthy controls, newly diagnosed primary breast cancer, non-metastatic breast cancer undergoing chemotherapy, and liver metastatic breast cancer. Plasma levels of the selected markers were measured using standard assays. Intriguingly, the results revealed that neither CXCL12 nor CA15-3 showed significant differences between breast cancer patients with and without liver metastasis, also demonstrating poor discriminatory power with low AUC values. In contrast, routine liver function tests proved more insightful: albumin levels were significantly lower in patients with BCLM, exhibiting moderate discriminatory ability (AUC 0.7267). More strikingly, ALP, ALT, and AST were significantly elevated in the BCLM group, with ALP (AUC 0.8693) and AST (AUC 0.9453) demonstrating high diagnostic accuracy for distinguishing patients with liver metastasis. Despite these strong individual discriminatory performances, the abstract concludes that none of the parameters were identified as an "independent risk factor" for liver metastasis. Overall, this abstract highlights that while novel chemokine CXCL12 and the common tumor marker CA15-3 may not serve as effective predictors or discriminators for BCLM, routine and readily available liver function tests, particularly ALP and AST, hold significant value in identifying patients with liver involvement. The high AUC values for ALP and AST strongly suggest their utility as diagnostic indicators for BCLM. The concluding statement regarding the lack of "independent risk factors" among the studied parameters warrants further clarification in the full manuscript, as it appears to contrast with the robust diagnostic accuracy observed for ALP and AST. Future research could benefit from exploring these markers within a multivariate predictive model, incorporating clinical and pathological features, and validating findings in larger, prospective cohorts to establish their true predictive and prognostic potential.

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