Department of Head and Neck Oncology and Surgery, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066, CX, Amsterdam, The Netherlands.
Department of Oral and Maxillofacial Surgery, University Medical Centre Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands.
BMC Cancer. 2018 Apr 5;18(1):385. doi: 10.1186/s12885-018-4315-8.
Lymph node metastasis (LNM) is a major determinant of prognosis and treatment planning of oral squamous cell carcinoma (OSCC). Cysteine cathepsins constitute a family of proteolytic enzymes with known role in the degradation of the extracellular matrix. Involvement in pathological processes, such as inflammation and cancer progression, has been proved. The aim of the study was to discover the clinicopathological and prognostic implications of cathepsin K (CTSK) expression in oral squamous cell carcinoma.
Eighty-three patients with primary OSCC, treated surgically between 1996 and 2000, were included. Gene expression data were acquired from a previously reported study. Human papilloma virus (HPV) status was previously determined by an algorithm for HPV-16. CTSK Protein expression was semi-quantitatively determined by immunohistochemistry in tumor and stromal cells. Expression data were correlated with various clinicopathological variables.
Elevated gene and protein expression of CTSK were strongly associated to LNM and perineural invasion (p < 0.01). Logistic regression analysis highlighted increased CTSK protein expression in tumor cells as the most significant independent factor of lymphatic metastasis (OR = 7.65, CI:2.31-23.31, p = 0.001). Survival analysis demonstrated CTSK protein expression in both stromal and tumor cells as significant indicators of poor 5-year disease specific survival (HR = 2.40, CI:1.05-5.50, p = 0.038 for stromal cells; HR = 2.79, CI:1.02-7.64, p = 0.045 for tumor cells).
Upregulation of CTSK seems to be associated with high incidence of lymphatic spread and poor survival in OSCC. CTSK could therefore serve as a predictive biomarker for OSCC.
淋巴结转移（LNM）是口腔鳞状细胞癌（OSCC）预后和治疗计划的主要决定因素。组织蛋白酶属于一组蛋白水解酶，已知在细胞外基质的降解中发挥作用。已经证明其参与了炎症和癌症进展等病理过程。本研究旨在探讨组织蛋白酶 K（CTSK）在口腔鳞状细胞癌中的表达与临床病理及预后的关系。
纳入 1996 年至 2000 年间接受手术治疗的 83 例原发性 OSCC 患者。基因表达数据来自先前的一项研究。HPV 状态通过 HPV-16 算法预先确定。通过免疫组织化学法在肿瘤细胞和基质细胞中半定量测定 CTSK 蛋白表达。表达数据与各种临床病理变量相关联。
CTSK 基因和蛋白表达升高与 LNM 和神经周围侵犯显著相关（p<0.01）。逻辑回归分析突出了肿瘤细胞中 CTSK 蛋白表达的增加是淋巴转移的最显著独立因素（OR=7.65，CI：2.31-23.31，p=0.001）。生存分析表明，肿瘤细胞和基质细胞中 CTSK 蛋白表达均为 5 年疾病特异性生存率的显著指标（HR=2.40，CI：1.05-5.50，p=0.038 基质细胞；HR=2.79，CI：1.02-7.64，p=0.045 肿瘤细胞）。
CTSK 的上调似乎与 OSCC 中较高的淋巴扩散发生率和较差的生存率相关。因此，CTSK 可以作为 OSCC 的预测生物标志物。
