Tumor cell-derived TGF-β at tumor center independently predicts recurrence and poor survival in oral squamous cell carcinoma
Tumor cell-derived TGF-β at tumor center independently predicts recurrence and poor survival in oral squamous cell carcinoma
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肿瘤中心肿瘤细胞衍生的TGF-β独立预测口腔鳞状细胞癌的复发和不良生存
DOI：
10.1111/jop.12888
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发表时间：
2019-09-01
影响因子：
3.3
通讯作者：
Ni, Yanhong
中科院分区：
文献类型：
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作者：
Lu, Zhanyi;Ding, Liang;Ni, Yanhong
转化生长因子- β (tgf - β)以肿瘤微环境依赖的方式在肿瘤发生过程中发挥其多功能（致瘤或抑瘤作用）。考虑到肿瘤的异质性，tgf - β在口腔鳞状细胞癌（OSCC）中的时空分布尚不清楚。方法对73例OSCC患者进行福尔马林固定石蜡包埋切片免疫染色，揭示肿瘤中心（TC）和侵袭性肿瘤前部（ITF）区域tgf - β的表达模式。结果肿瘤细胞、成纤维细胞样细胞（FLCs）和肿瘤浸润淋巴细胞（TILs）的tgf - β水平具有可比性，且与细胞类型无关。尽管肿瘤细胞（tgf - β（肿瘤细胞））中TC区tgf - β的阳性染色低于ITF区（89.0%对98.3%,P = 0.037）， FLCs (tgf - β (FLC))（86.3%对96.6%,P = 0.043）和TIL (tgf - β (TIL))(83.6%对94.8%,P = 0.044)， TC区tgf - β与不良临床结果相关，而非ITF区。在TC区，高tgf - β (Tumor cell)患者复发率高，高tgf - β (TIL)患者表现出较差的侵袭模式。值得注意的是，TC时高tgf - β（肿瘤细胞）预示着OSCC患者更短的总生存时间、无复发生存期和无病生存期，而高tgf - β (TIL)与生存时间没有关联。Cox回归分析表明，肿瘤细胞来源的tgf - β在TC是OSCC患者生存结局的独立危险因素。结论肿瘤细胞来源的tgf - β在TC区，而非ITF区，可能是预测OSCC患者疾病复发和预后不良的一个有希望的预测因素。
Background Transforming growth factor-beta (TGF-beta) 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-beta 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-beta, both at the regions of tumor center (TC) and invasive tumor front (ITF). Results The TGF-beta 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-beta than ITF in tumor cells (TGF-beta(Tumor cell)) (89.0% vs 98.3%; P = 0.037), FLCs (TGF-beta(FLC)) (86.3% vs 96.6%; P = 0.043), and TILs (TGF-beta(TIL)) (83.6% vs 94.8%; P = 0.044), respectively, TGF-beta at TC regions, not at ITF, correlated to poor clinical outcomes. At TC regions, patients with high TGF-beta(Tumor cell) had high recurrence rate, and patients with high TGF-beta(TIL) showed inferior worst pattern of invasion. Of note, high TGF-beta(Tumor cell) at TC predicted shorter overall survival time, recurrence-free survival, and disease-free survival in patients with OSCC, whereas high TGF-beta(TIL) had no association with survival time. Cox regression analyses indicated that tumor cell-derived TGF-beta at TC was an independent risk factor for survival outcome in patients with OSCC. Conclusions Tumor cell-derived TGF-beta at TC regions, but not at ITF, could be a promising predictor for disease recurrence and poor prognosis of patients with OSCC.