Cathepsin K 表达在唾液腺癌中的临床病理相关性；与患者预后的关系。

Clinicopathological correlation of Cathepsin K expression in salivary gland carcinomas; relation to patients` outcome.

机构信息

Oral Pathology Department, Faculty of Dentistry, Mansoura University, Mansoura, Egypt.

出版信息

Diagn Pathol. 2023 May 17;18(1):66. doi: 10.1186/s13000-023-01353-5.

DOI:10.1186/s13000-023-01353-5

PMID:37198626

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10190108/

Abstract

BACKGROUND

Salivary gland carcinomas (SGCs) represent various groups of tumors that demonstrate marked diversity in their prognosis owing to different histology and clinical characteristics. One of the poor prognostic indicators is distant metastasis which is considered the major reason for death in SGC patients. Discovering new biomarkers is urgently required to aid in the detection of cancer onset and progression. Cathepsin K (CTSK), the lysosomal cysteine protease has a principal role in cancer invasion and progression through interaction with the tumor microenvironment, degradation of extracellular membrane proteins and destruction of the elastic lamina of blood vessels. In the English literature, little information was present about the role of CTSK in SGCs. The current study aimed to assess the immunohistochemical expression of CTSK in SGCs and correlate its expression to different clinicopathologic parameters.

METHODS

The retrospective study applied to 45 cases of SGCs categorized as high-grade (33 cases) and low-grade SGCs (12 cases) following the criteria of WHO classification (2017) of head and neck tumors. All patients clinicopathological and follow-up records were retrieved. The following statistical tests were used to study the variance of CTSK expression in SGCs concerning different clinicopathological parameters; Pearsons Chi-square test, unpaired two-tailed student t-test, One-way ANOVA, and Post Hoc tests. Disease-free survival (DFS) and Overall survival (OS) were calculated and displayed with the Kaplan-Meier strategy and analyzed with the log-rank test. Univariate and multivariate survival analyses were performed with Cox regression. A P-value lesser than 0.05 was considered statistically significant.

RESULTS

Strong CTSK expression was significantly related to high-grade SGCs (P = 0.000), large infiltrating carcinomas (P = 0.000), presence of nodal (P = 0.041) and distant metastasis (P = 0.009), advanced TNM clinical stage (P = 0.000), the incidence of recurrence (P = 0.009), and reduced DFS (P = 0.006). Distant metastasis was the independent predictor for DFS using Cox regression model.

CONCLUSIONS

CTSK has a great role in cancer progression by triggering many signaling pathways. Its level in cancerous tissue is considered an effective index for predicting the severity and prognosis of cancer. Therefore, we indicate its utility as a prognostic tool and therapeutic target for cancer treatment.

TRIAL REGISTRATION

Retrospectively registered.

摘要

背景

唾液腺癌（SGCs）代表了各种肿瘤群体，由于其组织学和临床特征的不同，其预后存在显著差异。远处转移是不良预后指标之一，被认为是 SGC 患者死亡的主要原因。因此，迫切需要发现新的生物标志物来辅助癌症的早期发现和进展。组织蛋白酶 K（CTSK）是溶酶体半胱氨酸蛋白酶，通过与肿瘤微环境相互作用、降解细胞外膜蛋白和破坏血管弹性层，在癌症侵袭和进展中发挥主要作用。在英文文献中，关于 CTSK 在 SGCs 中的作用的信息很少。本研究旨在评估 CTSK 在 SGCs 中的免疫组织化学表达，并将其表达与不同的临床病理参数相关联。

方法

本回顾性研究应用于 45 例 SGCs 病例，根据头颈部肿瘤的世卫组织（2017 年）分类标准，分为高级别（33 例）和低级别 SGCs（12 例）。检索所有患者的临床病理和随访记录。采用 Pearson 卡方检验、两独立样本 t 检验、单因素方差分析和事后检验等统计学方法，研究 CTSK 在 SGCs 中不同临床病理参数的表达差异。无病生存（DFS）和总生存（OS）用 Kaplan-Meier 策略计算和显示，用对数秩检验进行分析。采用 Cox 回归进行单因素和多因素生存分析。P 值小于 0.05 被认为具有统计学意义。

结果

CTSK 强表达与高级别 SGCs（P=0.000）、大浸润性癌（P=0.000）、淋巴结（P=0.041）和远处转移（P=0.009）、晚期 TNM 临床分期（P=0.000）、复发发生率（P=0.009）和 DFS 降低（P=0.006）显著相关。远处转移是 Cox 回归模型中 DFS 的独立预测因素。