Prognostic and Clinicopathological Significance of Cytocapsular Tubes in Oral Squamous Cell Carcinoma.
Prognostic and Clinicopathological Significance of Cytocapsular Tubes in Oral Squamous Cell Carcinoma.
复制标题
口腔鳞状细胞癌细胞囊管的预后和临床病理学意义。
DOI：
10.1111/jop.13323
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Cheng Wang
中科院分区：
文献类型：
--
作者：
Wenjin Wang;N. Xie;Chen Yi;M. Zhang;G. Xiong;Xiuyun Xu;J. Hou;Cheng Wang
背景
细胞被膜管（CT）为癌细胞的相互连接和多向运动提供了膜通道，有助于癌细胞的运输和转移。然而，口腔鳞状细胞癌（OSCC）中CT的临床病理学意义尚未被记录。在此，我们的目的是确定CT和评估其在口腔鳞癌的临床病理意义。
方法
使用Operetta CLS™高含量分析系统检测来源于在3D Matrigel基质中培养的OSCC细胞的CT。然后，应用pan-cadherin和γ-actin免疫组化染色技术检测4 NQO诱导的小鼠口腔鳞癌组织、口腔鳞癌异种移植瘤和88例人原发性口腔鳞癌组织中的CT。最后，应用Kaplan-Meier法和考克斯回归分析进一步探讨CT在口腔鳞癌中的预后价值和临床病理意义。
结果
在3D Matrigel基质中的OSCC细胞中观察CT。在体内，CT经常在4 NQO诱导的鼠OSCC组织、OSCC异种移植物和人原发性OSCC样品中鉴定。CT密度与T分期、淋巴结转移、分化程度、浸润深度、肿瘤出芽、TNM分期及复发密切相关。重要的是，高CT密度表明OSCC患者的总生存期（OS）和无进展生存期（PFS）降低。考克斯回归模型显示CT可作为OS和PFS的预后因素。
结论
与细胞迁移和侵袭相关的CT在口腔鳞癌中很容易被识别，似乎是一种新的具有转移风险的患者的生物标志物。
BACKGROUND
Cytocapsular tubes (CTs) provide membranous channels for cancer cells interconnection and multidirectional locomotion, which facilitates 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 its clinicopathological significance in OSCC.
METHODS
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.
RESULTS
CTs were observed in OSCC cells in a 3D Matrigel matrix. In vivo, CTs are 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 indicates a decreased overall survival (OS) and progression-free survival (PFS) in OSCC patients. Cox regression models showed that CTs can serve as a prognostic factor for OS and PFS.
CONCLUSION
CTs, which is correlated with cell migration and invasion, can be readily identified in OSCC and appears to be a novel biomarker for patients at risk of metastasis.