Jonnathan Guadalupe Santillán-Benítez1, Hugo Mendieta-Zerón2, Leobardo Manuel Gómez-Oliván3, Angel Ordóñez Quiroz4, Juan Jueventino Torres-Juárez5, Juan Manuel González-Bañales6. 1. Molecular Biology Laboratory, Medical Research Center (CICMED), Autonomous University of the State of Mexico (UAEMex), Toluca, México C.P. 50130, Mexico; Toxicology Laboratory, Pharmacy Department, Faculty of Chemistry, UAEMex, Toluca, México C.P. 50120, Mexico. Electronic address: jonnathangsb@yahoo.com.mx. 2. Molecular Biology Laboratory, Medical Research Center (CICMED), Autonomous University of the State of Mexico (UAEMex), Toluca, México C.P. 50130, Mexico. Electronic address: mezh_74@yahoo.com. 3. Toxicology Laboratory, Pharmacy Department, Faculty of Chemistry, UAEMex, Toluca, México C.P. 50120, Mexico. Electronic address: lmgomezo@uaemex.mx. 4. Toxicology Laboratory, Pharmacy Department, Faculty of Chemistry, UAEMex, Toluca, México C.P. 50120, Mexico. Electronic address: aoq_27@yahoo.com.mx. 5. Maternal-Perinatal Hospital "Mónica Pretelini" (HMPMP), Toluca, México, C.P. 50130, Mexico. Electronic address: juantorresmd@yahoo.com.mx. 6. Maternal-Perinatal Hospital "Mónica Pretelini" (HMPMP), Toluca, México, C.P. 50130, Mexico. Electronic address: zagi_jm@hotmail.com.
Abstract
INTRODUCTION: Breast cancer is a disease that arises from the accumulation of alterations in the genome of cells that make up the mammary gland. The Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway has been reported to participate in the development of breast cancer and is activated by adipocytokines such as leptin, which are elevated in obesity. In contrast, alterations in suppressor of cytokine signaling 3 (SOCS3) gene expression have been found in patients with decreased breast cancer metastasis. OBJECTIVE: The current study sought to identify whether JAK2, STAT3 and SOCS3 gene expression is associated with body mass index (BMI) and breast cancer. METHODS: This was a cross-sectional prospective study. JAK2, STAT3 and SOCS3 gene expression levels were determined using RT-qPCR from the biopsies of 26 patients with breast cancer and 43 patients with benign breast lesions. We compared the expression of these genes, relative to the housekeeping genes, ACTB and GAPDH, against BMI, clinical stage and immunohistochemistry. RESULTS: STAT3 gene expression was increased in breast cancer patients (p≤0.001; AUC=0.65; AUC 95% CI: 0.5-0.8), and SOCS3 expression was decreased in obese patients with benign breast lesions (p≤0.001; AUC=0.51; AUC 95% CI: 0.36-0.65). With regard to the clinical stage, there were significant differences in STAT3 gene expression between stage II and III (p≤0.011) and stage II and IV (p≤0.033) breast cancers. Among all women, there was a positive correlation between JAK2 and STAT3 expression (R=0.493, p=0.000). In addition, breast cancers that were negative for HER2 were associated with JAK2 and SOCS3 (R=0.645, p=0.003). CONCLUSION: High levels of STAT3 expression were associated with early stages of breast cancer development and patients in the control group with obesity showed higher expression of SOCS3 regarding overweight.
INTRODUCTION:Breast cancer is a disease that arises from the accumulation of alterations in the genome of cells that make up the mammary gland. The Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway has been reported to participate in the development of breast cancer and is activated by adipocytokines such as leptin, which are elevated in obesity. In contrast, alterations in suppressor of cytokine signaling 3 (SOCS3) gene expression have been found in patients with decreased breast cancer metastasis. OBJECTIVE: The current study sought to identify whether JAK2, STAT3 and SOCS3 gene expression is associated with body mass index (BMI) and breast cancer. METHODS: This was a cross-sectional prospective study. JAK2, STAT3 and SOCS3 gene expression levels were determined using RT-qPCR from the biopsies of 26 patients with breast cancer and 43 patients with benign breast lesions. We compared the expression of these genes, relative to the housekeeping genes, ACTB and GAPDH, against BMI, clinical stage and immunohistochemistry. RESULTS:STAT3 gene expression was increased in breast cancerpatients (p≤0.001; AUC=0.65; AUC 95% CI: 0.5-0.8), and SOCS3 expression was decreased in obesepatients with benign breast lesions (p≤0.001; AUC=0.51; AUC 95% CI: 0.36-0.65). With regard to the clinical stage, there were significant differences in STAT3 gene expression between stage II and III (p≤0.011) and stage II and IV (p≤0.033) breast cancers. Among all women, there was a positive correlation between JAK2 and STAT3 expression (R=0.493, p=0.000). In addition, breast cancers that were negative for HER2 were associated with JAK2 and SOCS3 (R=0.645, p=0.003). CONCLUSION: High levels of STAT3 expression were associated with early stages of breast cancer development and patients in the control group with obesity showed higher expression of SOCS3 regarding overweight.