ABSTRACT
BACKGROUND: Initiation, promotion, progression, and metastasis of mammary tumors are mediated by dysregulation of multiple genes involved in various signaling pathways. Expressional variation of these molecules significantly influences cancer cell proliferation in breast cancer. AIMS AND OBJECTIVES: In the current study, tumor necrosis factor-alpha (TNF-α) and its downstream effector nuclear factor kappa-B1 (NF-κB1) mean transcript levels were explored and associated with molecular subtypes in breast cancer cohort of Pakistan. Freshly excised tumors (n = 150) along with background tissues were collected for RNA isolation and cDNA synthesis. MATERIALS AND METHODS: Quantitative polymerase chain reaction was carried out for quantification of TNF-α, NF-κB1, and ß-actin gene transcripts along with estrogen receptor, progesterone receptor, HER2, and Ki-67, followed by statistical analysis. RESULTS: For TNF-α and NF-κB1, 95% and 77% of the cohort was found to be positive, respectively. Both of these molecules were found to be significantly upregulated in tumors when compared against their respective controls (P < 0.0001). Association of TNF-α and NF-κB1 with late clinical stages, poorly differentiated tumors, increased tumor size, nodal involvement, and metastasis was observed to be statistically significant (P < 0.05). Strong positive correlation was established between TNF-α and NF-κB1(r = 0.465, P< 0.05). Moreover, mean transcript levels of TNF-α and NF-κB1 were significantly elevated in Luminal A and Luminal B subtypes of breast cancer patients, respectively. CONCLUSION: Strong positive correlation between TNF-α and NF-κB1 proposed the putative role of these molecules as prognostic biomarkers in breast cancer.
Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/pathology , Lymphatic Metastasis/diagnosis , NF-kappa B p50 Subunit/metabolism , Tumor Necrosis Factor-alpha/metabolism , Adult , Breast/pathology , Breast/surgery , Breast Neoplasms/diagnosis , Breast Neoplasms/surgery , Case-Control Studies , Disease Progression , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Lymphatic Metastasis/pathology , Middle Aged , Neoplasm Staging , Pakistan , Prognosis , Up-RegulationABSTRACT
BACKGROUND/AIM: Constitutive activation of Sonic hedgehog (SHH) has been observed in different types of cancers. In the present study, expressional profiling of SHH in a breast cancer cohort (n=150) of a Pakistani population and its association with different molecular subtypes have been explored. MATERIALS AND METHODS: qRT-PCR and IHC were performed for expression analysis of SHH and its association with ER, PR, HER2 and Ki-67 were also statistically analyzed. RESULTS: A significant over-expression of SHH was observed in tumor tissues in comparison to their respective controls (p<0.0001). A strong positive correlation was seen between SHH and proliferation marker (r=0.635, p=0). SHH expression was significantly high among patients with advanced tumor grade, stage, nodal involvement and metastasis. Furthermore, both luminal-B and triple-negative subtypes of cohort showed increased expression of SHH. CONCLUSION: Based on these findings, SHH may be used as a potential biomarker for breast carcinogenesis.
