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Abstract

Several studies have shown breast cancer BC metastasis is the second leading cause of cancer-related deaths among women. To prevent cancer metastasis, it is crucial to understand how the metastasis process unfolds and to pinpoint suitable targets for effective treatments. This study focuses on COL1A1 (Collagen I) and COL12A1 (Collagen XII) which are major players of tumor microenvironment and how their expression levels can serve as an early metastatic marker to save the lives of BC patients. Rationale of the study is to analyze the gene expression of COL1A1, COL12A1, Lnc SNHG5, TWIST1 and LOXL2 in blood samples of BC patients, to identify their relation to the pre-metastatic niche formation and metastatic potential of tumors. This research uses primary data. A total of 32 blood samples collected from BC patients as well as 15 healthy donors as control. We performed RNA extraction from the tumor samples by using Trizol and quantification of RNA was done by Nanodrop and gel electrophoresis. The cDNA was synthesized from 1 µg of total RNA which was diluted at 1:4. RT-qPCR analysis was utilized to quantify the expression of COL1A1, COL12A1, Lnc SNHG5, TWIST1 and LOXL2 and to measure the mRNA level of these genes. The results revealed that the expression of COL1A1, Lnc SNHG5, TWIST1 and LOXL2 were upregulated in BC patients whereases mRNA level of COL12A1 is decreased in patient sample. Kaplan Meier analysis showed that increase in COL1A1 is associated with decreased distant metastatic free survival of the patients which is vice versa in the case of COL12A1. Further it is observed that high expression of COL1A1 is particularly found in patients with high grade tumor/ metastasis. Since COL1A1 and COL12A1 are a significant contributor in development of metastatic niche leading to metastasis therefore breast cancer patients with high tumor grade are exhibiting higher expression of these genes. Levels of COL1A1, and COL12A1 can be utilized as an early diagnostic marker for breast cancer metastasis, and with enhanced analysis methods, a rapid blood-based test can be designed for early diagnosis. Studies have also revealed that the development of pre-metastatic niches (PMNs) in BC plays a vital role in cancer metastasis, leading to high mortality rates. Targeting and understanding the multifaceted mechanisms of the COL1A1, COL12A1, Lnc SNHG5, TWIST1 and LOXL2 that contribute to PMN formation offer new opportunities for potential diagnostic and therapeutic strategies, aiming to prevent cancer metastasis at an early stage and improve outcomes for breast cancer patients.