Orchestrated expression of vasculogenic mimicry and laminin‐5γ2 is an independent prognostic marker in oral squamous cell carcinoma

Abstract

Vasculogenic mimicry (VM), an endothelial cell–independent alternative mechanism of blood supply to the malignant tumour, has long been considered as an adverse prognostic factor in many cancers. The correlation of VM with laminin‐5γ2 and the assessment of their harmonized expression as an independent risk factor have not been elucidated yet in oral squamous cell carcinoma (OSCC). CD31/PAS staining stratified 116 clinically diagnosed OSCC specimens into VM+ and VM− cohorts. The expression pattern of laminin‐5γ2 and its upstream modulator MMP2 was evaluated by immunohistochemistry and Western blot. The Kaplan–Meier and Cox regression analyses were performed to assess the survival and prognostic implications. The presence of VM demonstrated a significant correlation with the expression of laminin‐5γ2 (p < .001) and MMP2 (p < .001). This pattern was mirrored by the significant upregulation of laminin‐5γ2 and MMP2 in VM+ cohorts compared with the VM− ones. Furthermore, co‐expression of VM and laminin‐5γ2 was significantly associated with tumour grade (p = .010), primary tumour size (p < .001), lymph node metastasis (p = .001) and TNM stages (p < .001) but not with patients' age, gender, tobacco and alcohol consumption habit. Vasculogenic mimicry and laminin‐5γ2 double‐positive cohort displayed a significantly poorer disease‐free survival (DFS) and overall survival (OS). Vasculogenic mimicry, laminin‐5γ2 and their subsequent dual expression underlie a significant prognostic value for DFS [hazard ratio (HR) = 9.896, p = .028] and OS [HR = 21.401, p = .033] in OSCC patients. Together, our findings imply that VM along with laminin‐5γ2 is strongly linked to the malignant progression in OSCC and VM and laminin‐5γ2 coordination emerges as a critical prognostic biomarker for OSCC.

Lupeol and Paclitaxel cooperate in hindering hypoxia induced vasculogenic mimicry via suppression of HIF-1α-EphA2-Laminin-5γ2 network in human oral cancer

“…Immunohistochemistry staining (IHC) was performed according to the manufacturer’s instruction (Millipore, IHC Select DAB150 Immuno‐peroxidase secondary detection system kit) on 5‐micron sections from the FFPE tumor blocks as per our previously described methods (Saha et al 2022; Ray et al 2021; Mitra et al 2020). Primary antibodies against CD‐31 or PECAM‐1, HIF‐1α, VE‐Cadherin, EphA2, pERK1/2, MMP2, Laminin‐5γ2, E‐Cadherin, Vimentin, Snail, Twist were used for IHC.…”

“…Primary antibodies against CD-31 or PECAM-1, HIF-1α, VE-Cadherin, EphA2, pERK1/2, MMP2, Laminin-5γ2, E-Cadherin, Vimentin, Snail, Twist were used for IHC. The final IHC score was determined by considering intensity of staining and proportion (%) of stained cells as described earlier (Saha et al 2022).…”

“…However, their active networking in the context of critical nodal role of HIF‐1α has not been established in OSCC. In our earlier study we have depicted the prognostic significance of VM in coordination with Laminin‐5γ2 expression in OSCC patient cohorts (Saha et al 2022). Here, we aim to further investigate the mechanistic link between HIF‐1α and Laminin‐5γ2 in reshaping of ECM and simultaneous formation of VM architecture in OSCC which may be a potential therapeutic intervention in OSCC with high VM propensity.…”