Prognostic and clinicopathological significance of cytocapsular tubes in oral squamous cell carcinoma.

Abstract

Cytocapsular tubes (CTs) provide membranous channels for cancer cells interconnection and multidirectional locomotion, which facilitate cancer cell transportation and metastasis. However, the clinicopathological significance of CTs has not been documented in oral squamous cell carcinoma (OSCC). Herein, we aimed to identify CTs and assess theirclinicopathological significance in OSCC. Operetta CLS™ high-content analysis system was used to detect the CTs originated from OSCC cells cultured in a 3D Matrigel matrix. Then, pan-cadherin and γ-actin immunostaining were performed to identify CTs in 4NQO-induced murine OSCC tissues, OSCC xenografts and 88 human primary OSCC samples. Finally, the prognostic value and clinicopathological significance of CTs in OSCC were further examined by using the Kaplan-Meier method and Cox regression analysis. CTs were observed in OSCC cells in a 3D Matrigel matrix. In vivo, CTs were frequently identified in 4NQO-induced murine OSCC tissues, OSCC xenografts and human primary OSCC samples. CTs density was significantly associated with T stage, lymph node metastasis, differentiation, invasive depth, tumor budding, TNM stage and tumor recurrence. Importantly, the high-CTs density indicated a decreased overall survival (OS) and progression-free survival (PFS) in OSCC patients. Cox regression models showed that CTs could serve as a prognostic factor for OS and PFS. CTs, which are correlated with the cell migration and invasion, can be readily identified in OSCC and appear to be a novel biomarker for patients at risk of metastasis.