Deregulation of extracellular matrix modeling with molecular prognostic markers revealed by transcriptome sequencing and validations in Oral Tongue squamous cell carcinoma

Abstract

Oral Tongue Squamous Cell Carcinoma (OTSCC), a distinct sub-group of head and neck cancers, is characteristically aggressive in nature with a higher incidence of recurrence and metastasis. Recent advances in therapeutics have not improved patient survival. The phenomenon of occult node metastasis, even among the purportedly good prognosis group of early-stage and node-negative tongue tumors, leads to a high incidence of locoregional failure in OTSCC which needs to be addressed. In the current study, transcriptome analysis of OTSCC patients identified the key genes and deregulated pathways. A panel of 26 marker genes was shortlisted and validated using real-time PCR in a prospective cohort of 100 patients. The gene expression was correlated with clinicopathological features including occult node metastasis, survival, and therapeutic outcome. The up-regulation of a panel of 6 genes namely, matrix metalloproteinase 9 (MMP9), Laminin subunit Gamma 2 (LAMC2), Desmoglein 2 (DSG2), Plasminogen Activator Urokinase (PLAU), Forkhead Box M1 (FOXM1), and Myosin 1B (MYO1B) was associated with failure of treatment in the early stage (T1, T2). Up-regulation of Tenacin C (TNC) and Podoplanin (PDPN) was significantly correlated with occult node positivity. Immunohistochemical analysis of LAMC2, MMP9, and E-Cadherin (ECAD) confirmed these markers to be indicators of poor prognosis. We propose this panel of valuable prognostic markers can be clinically useful to identify poor prognosis and occult node metastasis in OTSCC patients.

Correlation of mitotic activity and Ki 67 with BR score and molecular classification in carcinoma breast

“…Thangaraj et al found a strong connection between grade and Ki 67 in a retrospective examination of the Ki-67 index and its prognosis. 18 Significance in Over 800 primary breast cancer cases. Ki-67 expression levels were shown to be substantially linked with histological grade in all patients in research by Liang et al (p=0.001).…”

Invasion-Associated Reorganization of Laminin 332 in Oral Squamous Cell Carcinomas: The Role of the Laminin γ2 Chain in Tumor Biology, Diagnosis, and Therapy

“…Indeed, there are several reports on the diagnostic and predictive value of Lng2 immunohistochemistry in OSCCs. Among others, a correlation has been shown between a diffuse expression of Lng2 in disseminating and infiltrating tumor cells, with higher grades of malignancy, poor prognosis, and a higher risk for nodal metastasis observed in patients with tongue cancer [66][67][68][69]. Furthermore, shorter life expectancy in OSCCs with an increased number of Lng2-positive tumor cells [70], an elevated risk for transformation in Lng2-positive pre-neoplastic mucosal lesions [71,72], as well as a higher risk for nodal metastasis [20,73,74] could be evidenced.…”

Paradoxical Roles of Desmosomal Components in Head and Neck Cancer

“…The results suggest that these desmosomal components may work as tumor suppressors in HNC. However, the functional study of gain or loss and immunohistochemistry identification of desmosomal components have revealed contradictory roles for some desmosome members, including DSG2 [65,[73][74][75], DSG3 [26,65,66,76], PKP1 [27,77,78], and PG [70,79,83] in HNC, suggesting that the role of the desmosomal components in HNC may be affected by some other signal transduction molecules or/and modifications related to the tumor microenvironment. Additionally, like other tumors, subcellular location, PTM, inactivation by proteolytic cleavage, and the biogenesis of regulating extracellular vesicles (EVs) may also affect the role of desmosomes in HNC.…”