Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, People's Republic of China.
Department of Basic Science of Stomatology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
J Cell Biochem. 2019 Sep;120(9):14348-14359. doi: 10.1002/jcb.28669. Epub 2019 May 29.
Collagen is a core protein that maintains the homeostasis of the extracellular matrix (ECM), and its dysregulation in human cancers has attracted increasing attention. In tumors, increased lysyl oxidase (LOX)-catalyzed collagen cross-linking plays a critical role in collagen dysregulation. However, the expression patterns of LOX and collagen and their clinicopathological significance in oral squamous cell carcinoma (OSCC) have not been well established.
The LOX mRNA expression in OSCC was measured by RT-PCR and bioinformatics analysis. LOX protein expression and total collagen content were identified by immunohistochemistry or Masson's trichrome staining in a retrospective cohort of primary OSCC samples, respectively. Moreover, the associations between LOX and collagen expression and various clinicopathological parameters or patient survival were assessed.
LOX mRNA was overexpressed in OSCC samples. Higher expression of LOX, collagen content or co-overexpression of LOX and collagen was significantly associated with aggressive clinicopathological features. Importantly, aberrant expression of LOX, collagen content, or both were markedly correlated with decreased overall and disease-free survival (P < 0.05). Moreover, univariate and multivariate Cox models analyses indicated that LOX, collagen content or their combination could serve as an independent prognostic predictor for OSCC patients. ROC analysis further revealed that the combination of LOX and collagen was superior to parameter alone as a prognostic predictor.
Our findings reveal that elevated LOX and collagen content significantly corelate with aggressiveness and worse prognosis in OSCC.
胶原蛋白是维持细胞外基质（ECM）内稳态的核心蛋白，其在人类癌症中的失调引起了越来越多的关注。在肿瘤中，赖氨酰氧化酶（LOX）催化的胶原蛋白交联增加在胶原蛋白失调中起关键作用。然而，LOX 和胶原蛋白的表达模式及其在口腔鳞状细胞癌（OSCC）中的临床病理意义尚未得到很好的确定。
通过 RT-PCR 和生物信息学分析测量 OSCC 中的 LOX mRNA 表达。通过免疫组织化学或 Masson 三色染色分别在原发性 OSCC 样本的回顾性队列中鉴定 LOX 蛋白表达和总胶原蛋白含量。此外，评估了 LOX 和胶原蛋白表达与各种临床病理参数或患者生存之间的关系。
LOX mRNA 在 OSCC 样本中过表达。LOX、胶原蛋白含量或 LOX 和胶原蛋白的共过表达较高与侵袭性临床病理特征显著相关。重要的是，LOX、胶原蛋白含量或两者的异常表达与总生存率和无病生存率降低显著相关（P<0.05）。此外，单因素和多因素 Cox 模型分析表明，LOX、胶原蛋白含量或其组合可作为 OSCC 患者的独立预后预测因子。ROC 分析进一步表明，LOX 和胶原蛋白的组合作为预后预测因子优于单独参数。
我们的研究结果表明，LOX 和胶原蛋白含量的升高与 OSCC 的侵袭性和预后不良显著相关。
