Implicating clinical utility of altered expression of PTCH1 & SMO in oral squamous cell carcinoma.

INTRODUCTION: Oral cancer poses a significant burden on public health in India, with higher incidence and mortality rates. Despite advancements in treatment modalities, prognosis remains poor due to factors such as localized recurrence and lymph node metastasis, potentially influenced by cancer stem cells. Among signaling pathways implicated in CSC regulation, the Hedgehog pathway plays a crucial role in oral squamous cell carcinoma (OSCC). MATERIAL & METHODS: 97 OSCC patients' tissue samples were collected and subjected to RNA isolation, cDNA synthesis and quantitative real-time PCR to analyze PTCH1 and SMO expression. Protein expression was assessed through immunohistochemistry. Clinicopathological parameters were correlated with gene and protein expression. Statistical analysis included Pearson chi-square tests, co-relation co-efficient tests, Kaplan-Meier survival analysis and ROC curve analysis. RESULTS: PTCH1 expression correlated with lymphatic permeation (p = 0.002) and tumor stage (p = 0.002), while SMO expression correlated with lymph node status (p = 0.034) and tumor stage (p = 0.021). PTCH1 gene expression correlated with lymph node status (p = 0.024). High PTCH1 gene expression was associated with shorter survival in tongue cancer patients. ROC curve analysis indicated diagnostic potential for PTCH1 and SMO gene and cytoplasmic SMO expression in distinguishing malignant tissues from adjacent normal tissues. CONCLUSION: PTCH1 and SMO play a crucial role in oral cancer progression, correlating with tumor stages and metastatic potential. Despite not directly influencing overall survival, PTCH1 expression at specific anatomical sites hints at its prognostic implications. PTCH1 and SMO exhibit diagnostic potential, suggesting their utility as molecular markers in oral cancer management and therapeutic strategies.

A clinicopathological exploration of Hedgehog signaling: implications in oral carcinogenesis.

INTRODUCTION: Hedgehog Signaling, a basic cancer stem cell pathway, plays a major role during the embryonic development, is known to play a quiescent role in adults. However, aberrant activation of Hedgehog signaling in adults is known to play a role in cancer development. Hence, the aim of the study was to identify the role of Hedgehog signaling pathway in the Oral cancers. MATERIALS AND METHODS: The expression of Hedgehog signaling pathway was evaluated in 124 patients through the quantitative real-time PCR. The association between the gene expression and clinico-pathological parameters were analyzed using the Pearson chi-square test and survival analysis was carried out using Kaplan-Meier analysis. RESULTS: SHH and GLI1 was found to be significantly associated with the Lymph Node Status and SUFU was significantly associated with the Age. SMO and SUFU were found to have a worse prognosis in oral cancer patients. According to our findings, IHH plays a critical role in the activation of the HH signaling pathway in oral cancer. CONCLUSION: These findings back up the use of the Hedgehog signaling pathway as a biomarker for early disease prediction in oral cancer, as well as its role in tumor aggressiveness and invasiveness.

Nonhomologous end joining repair pathway molecules as predictive biomarkers for patients with oral squamous cell carcinoma.

PURPOSE: Nonhomologous end-joining (NHEJ) is critical for the repair of either pathologic double-strand breaks (DSBs) and/or for the repair of physiologic DSBs created during radiotherapy to kill the tumor cell. Therefore, patients with higher expression of NHEJ repair proteins might develop resistance to ionizing radiation, allowing the disease to recur. As cancer of the oral cavity is a serious health problem globally, the present study aimed to examine the expression of Ku70/80, X-ray repair cross-complementing protein 4 (XRCC4) and DNA ligase IV-core molecules of the NHEJ pathway in patients with oral cancer. MATERIALS AND METHODS: Protein expression of Ku70/80, XRCC4, and DNA ligase IV were studied by Immunohistochemistry and mRNA expression of Ku70 and Ku80 were studied using reverse transcription polymerase chain reaction. Data were analyzed statistically using SPSS. RESULTS: A univariate survival analysis revealed an association of Ku70 mRNA with shorter overall survival (OS). While protein expression of XRCC4 showed an association with reduced relapse-free survival and shorter OS. Multivariate survival analysis demonstrated that XRCC4 and DNA ligase IV are independent prognosticators for predicting adverse disease outcomes. CONCLUSION: Strong expression of repair proteins - XRCC4 and DNA ligase IV is associated with unfavorable disease outcome in patients with oral squamous cell carcinoma.

Role of epithelial - Stromal interaction protein-1 expression in breast cancer.

BACKGROUND AND AIMS: Epithelial stromal interaction protein-1 (EPSTI-1) is originally identified as stromal-fibroblast - induced gene in breast cancer. It was found to be involved in promotion of EMT, breast cancer invasion, metastasis and anchorage-independent growth in vitro. Strong expression was observed in various tissues as well as higher expression was observed in invasive breast cancer compared to normal breast. EPSTI-1 expression was evaluated from 106 pre-therapeutic breast cancer patients. EPSTI-1 expression was correlated with known clinico-pathological parameters of breast cancer to explore its role in breast carcinogenesis. SUBJECTS AND METHODS: EPSTI-1 expression was analyzed from the collected synchronous tissues [tumors, Malignant Lymph nodes (LN) and adjacent normal tissues (ANT)] of breast carcinoma patients (N = 106). The statistical correlation was performed using SPSS 16.0. RESULTS: In this study EPSTI-1 was significantly higher in LN compared to tumors (P < 0.001), and in tumors compared to ANT (P < 0.01) which is also reflected in ROC curve analysis (P < 0.0001). Further the small tumor size, stage I, grade I and tumors without stromal involvement exhibited significant lower expression compared to their counter parts. CONCLUSION: EPSTI-1 may have significant role in epithelial stromal interaction and disease extension. Moreover, it may be responsible for aggressive tumor behavior and involved in metastatic process which needs to be validated in larger cohort.