Tumor cell‐derived TGF‐β at tumor center independently predicts recurrence and poor survival in oral squamous cell carcinoma

Abstract

Background Transforming growth factor‐β (TGF‐β) exerts its versatile function (oncogenic or tumor suppressive role) during the carcinogenesis in tumor microenvironment‐dependent manner. Considering the tumor heterogeneity, spatial and temporal distribution of TGF‐β in oral squamous cell carcinoma (OSCC) remained to be elucidated. Methods Formalin‐fixed, paraffin‐embedded sections derived from 73 patients with OSCC were immunostained, revealing expression patterns of TGF‐β, both at the regions of tumor center (TC) and invasive tumor front (ITF). Results The TGF‐β levels on tumor cells, fibroblast‐like cells (FLCs), and tumor‐infiltrating lymphocytes (TILs) were comparable and showed to be cell‐type‐independent manner. Although TC regions harbored less positive staining of TGF‐β than ITF in tumor cells (TGF‐βTumor cell) (89.0% vs 98.3%; P = 0.037), FLCs (TGF‐βFLC) (86.3% vs 96.6%; P = 0.043), and TILs (TGF‐βTIL) (83.6% vs 94.8%; P = 0.044), respectively, TGF‐β at TC regions, not at ITF, correlated to poor clinical outcomes. At TC regions, patients with high TGF‐βTumor cell had high recurrence rate, and patients with high TGF‐βTIL showed inferior worst pattern of invasion. Of note, high TGF‐βTumor cell at TC predicted shorter overall survival time, recurrence‐free survival, and disease‐free survival in patients with OSCC, whereas high TGF‐βTIL had no association with survival time. Cox regression analyses indicated that tumor cell‐derived TGF‐β at TC was an independent risk factor for survival outcome in patients with OSCC. Conclusions Tumor cell‐derived TGF‐β at TC regions, but not at ITF, could be a promising predictor for disease recurrence and poor prognosis of patients with OSCC.

Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis

“…Our data revealed the presence of TGF-β2 in WPS-exposed oral epithelial cells as well as in HNSCC; previous studies have indicated the presence of TGF-β2 in cancer associated fibroblasts from OSCC [ 83 ] as well as in SCC cell lines [ 84 ]. Similar to our data, elevated TGF expression was significantly associated with shorter OS, RFS, and DFS in patients with OSCC [ 85 ]. The other type of cytokine identified in this study is IFNγ .…”

Tumor‐infiltrating lymphocyte‐derived MLL2 independently predicts disease‐free survival for patients with early‐stage oral squamous cell carcinoma

“…According the clinical guideline and previously reports, the expressive regions of MLL2 patterns in early‐stage OSCC were divided into two compartments: tumor center and invasive tumor front . Different cell types including TCs, FLCs, and TILs were distinguished according to their specific shapes and cell locations, consistent with international guidelines and our previous studies . Final decision was made based on the consensus by these two investigators.…”

“…Final immunohistochemical scores were calculated by multiplying the percentage score combined with the intensity score . The expression level of MLL2 and scores of Ki‐67 in each cell were defined as “Low” when under the median value and as “High” when equal to or greater than the median value . Representative IHC images are presented in Figure .…”

Inflammatory Mediators in Oral Cancer: Pathogenic Mechanisms and Diagnostic Potential

“…In OSCC, TGF-β is reported to promote tumorigenesis [ 17 ]. This is supported by the fact that OPMDs [ 18 ] and OSCC [ 19 , 127 ] express higher levels of TGF-β than healthy controls and that high TGF-β levels are associated with disease recurrence and poor prognosis in patients with OSCC [ 19 ]. There are different mechanisms by which TGF-β could act as a tumor promoter in oral cancer.…”