The role of lncRNA and miRNA in early diagnosis, treatment, prognosis and axillary metastasis in breast cancer

Breast cancer is the most common type of cancer in women worldwide. It also ranks first in cancer mortality in women. According to the World Health Organization (WHO) GLOBOCAN 2020 data, it is the most common cancer type among all cancers with approximately 2.3 million new cases and 11.7% rate (1). The presence of axillary metastases is an important criterion in the diagnosis, treatment and prognosis of breast cancer. Sentinel Lymph Node Biopsy (SLNB) is the gold standard in the investigation of axillary metastases in breast cancers. However, SLNB is an invasive method that prolongs the operation time. In recent years, alternative axillary metastasis detection methods have been investigated (2). Nowadays; lncRNA and miRNA studies in cancer patients have started to gain popularity and significant results have been obtained in these studies. It has also been demonstrated that various miRNAs have a vital effect on the pathogenesis of breast cancer. Long ncRNAs play a crucial role in various types of cancer, including breast cancer. Abnormal expression of lncRNAs contributes significantly to cancer initiation and progression in breast cancer (3, 4). In this study, in patients with early stage breast cancer treated in Pamukkale University General Surgery Clinic in the last 2 years; we studied serum miR150-5p and miR503-5p, lncRNA BLACAT1, a chemokine receptor protein Ccr2 and an apoptosis regulator Bcl-2 in preoperative blood samples. Thus, in this study; we investigated whether it is possible to detect the presence of axillary metastases in breast cancer not only from tissue samples but also from serum samples. We performed SLNB frozen study to confirm axillary metastases in breast cancer during the operation. In addition, we checked the presence of axillary metastases in the pathology samples with paraffin after the operation. Our study included 57 patients with a mean age of 53,15±12,82 years. According to the results of our study; When expression analyzes performed with the correlation of frozen sentinel lymph node results of the patients, only miR-503-5p expression showed 2,33-fold expression in patients with at least one malignant sentinel lymph node compared to patients with all benign sentinel lymph nodes. We found no significant difference in other markers. We also evaluated expression analyzes according to criteria important for treatment. When we analyzed according to their molecular classification, lncRNA BLACAT 1 expression was found to be significant with a 3,04-fold increase in Luminal B tumors and a 26,65-fold increase in HER2 tumors compared to other molecular subtypes. miR -150-5p was found to be significant by being expressed 2,93 times higher in Luminal B tumors compared to the others. We evaluated these markers correlation with age (which is important for prognosis), We observed that BLACAT1 was expressed 2,48 times downstream in patients over 50 years of age compared to patients under 50 years of age. We observed that mir-150-5p was expressed in the direction of a 2,50-fold increase in patients over 50 years of age compared to patients under 50 years of age, and it was evaluated as significant. When the correlation with family history, which is important for early diagnosis evaluated. We observed that BLACAT1 was significantly expressed 5,37 times downstream in patients with a family history of breast cancer compared to patients without a family history of breast cancer. We observed that miR-503-5p was significantly expressed 6,41 times upstream in patients with a family history of breast cancer compared to patients without a family history of breast cancer. We observed that mir-150-5p was significantly expressed 2,29 times upstream in patients with a family history of breast cancer compared to patients without a family history of breast cancer. Considering the correlation with Ki-67, which is important in diagnosis, treatment and prognosis; we found the expression of mir-503-5p to be significant in patients with Ki-67 synthesized more than 20%, showing an increase of 3,52 times compared to patients with Ki-67 expression less than 20%. In the expression of mir-150-5p, we evaluated as significant by showing an increase of 3,54 in patients with Ki-67 expressed more than 20% compared to the patients with Ki-67 expression less than 20%. As a result, in our study; We investigated the expression levels of breast cancer-associated miRNAs (miR-503-5p, miR150-5p) lncRNA BLACAT1, bcl2, ccr2 in preoperative serum samples in patients diagnosed with early stage breast cancer, without any additional cancer, and not received neoadjuvant chemotherapy. The changes of these parameters in preoperative serum samples are shown. According to our study, we thought that serum mir 503-5p expression could be used as a less invasive additional method compared to SLNB used for axillary metastasis detection. When evaluated with factors that are important for early diagnosis, treatment and prognosis, we thought that lncRNA BLACAT1, miR 503-5p and miR150-5p could provide an idea in terms of diagnosis, treatment and prognosis by looking at the serum samples of patients with early stage breast cancer who did not receive neoadjuvant chemotherapy. Keywords: miR150-5p, miR503-5p, BLACAT1, molecular classification, sentinel lymph nod