Cathepsin K: A Versatile Potential Biomarker and Therapeutic Target for Various Cancers

Qian, Die; He, Liyun; Zhang, Qing; Li, Wenqing; Tang, Dandan; Wu, Chunjie; Yang, Fei; Li, Ké; Zhang, Hong

doi:10.3390/curroncol29080471

Cited by 25 publications

(12 citation statements)

References 183 publications

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“…CTSK overexpression has also been observed in malignant tumours and heart failure [ 24 ]. This enzyme is highly expressed in the sera and tissues of patients with cancer [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomics study of primary and recurrent adamantinomatous craniopharyngiomas

Deng,

Lei,

Liu

et al. 2024

Clin Proteom

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Background Adamantinomatous craniopharyngiomas (ACPs) are rare benign epithelial tumours with high recurrence and poor prognosis. Biological differences between recurrent and primary ACPs that may be associated with disease recurrence and treatment have yet to be evaluated at the proteomic level. In this study, we aimed to determine the proteomic profiles of paired recurrent and primary ACP, gain biological insight into ACP recurrence, and identify potential targets for ACP treatment. Method Patients with ACP (n = 15) or Rathke’s cleft cyst (RCC; n = 7) who underwent surgery at Sanbo Brain Hospital, Capital Medical University, Beijing, China and received pathological confirmation of ACP or RCC were enrolled in this study. We conducted a proteomic analysis to investigate the characteristics of primary ACP, paired recurrent ACP, and RCC. Western blotting was used to validate our proteomic results and assess the expression of key tumour-associated proteins in recurrent and primary ACPs. Flow cytometry was performed to evaluate the exhaustion of tumour-infiltrating lymphocytes (TILs) in primary and recurrent ACP tissue samples. Immunohistochemical staining for CD3 and PD-L1 was conducted to determine differences in T-cell infiltration and the expression of immunosuppressive molecules between paired primary and recurrent ACP samples. Results The bioinformatics analysis showed that proteins differentially expressed between recurrent and primary ACPs were significantly associated with extracellular matrix organisation and interleukin signalling. Cathepsin K, which was upregulated in recurrent ACP compared with that in primary ACP, may play a role in ACP recurrence. High infiltration of T cells and exhaustion of TILs were revealed by the flow cytometry analysis of ACP. Conclusions This study provides a preliminary description of the proteomic differences between primary ACP, recurrent ACP, and RCC. Our findings serve as a resource for craniopharyngioma researchers and may ultimately expand existing knowledge of recurrent ACP and benefit clinical practice.

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“…CTSK overexpression has also been observed in malignant tumours and heart failure [ 24 ]. This enzyme is highly expressed in the sera and tissues of patients with cancer [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomics study of primary and recurrent adamantinomatous craniopharyngiomas

Deng,

Lei,

Liu

et al. 2024

Clin Proteom

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“…Strong CTSK expression was related to poor clinicopathological parameters such as (high-grade carcinomas, large infiltrating carcinomas, presence of nodal involvement, presence of distant metastasis, carcinomas of advanced TNM clinical stage, presence of recurrence, and reduced DFS). The great role of CTSK in cancer progression through triggering many signaling pathways indicates its utility as a therapeutic target for cancer treatment [ 25 , 72 , 73 ]. Therefore, the level of CTSK in cancer tissue is considered an effective index for predicting the severity and prognosis of cancers (Table 12 ).…”

Section: Discussionmentioning

confidence: 99%

“…Many pathways may be triggered in the mechanism by which CTSK could promote the proliferation, invasion, and migration of tumor cells (RANK/RANKL, TGF-B, mTOR, and Wnt/β-catenin pathways). Recently, the utility of CTSK inhibitors in cancer treatment reached some progress [ 25 ]. In the literature review, little information was present about the role of CTSK in salivary gland tumors.…”

Section: Introductionmentioning

confidence: 99%

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

Elhendawy

Soliman

2023

Diagn Pathol

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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; Pearson`s 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.

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“…There are also many studies on the potential relationship between cathepsins and tumors, which means that certain cathepsins are involved in the occurrence and development of tumors. Numbers of reports have found that cathepsin K promotes breast cancer [7], lung cancer, prostate cancer [8,9] and soft tissue sarcoma [10,11]. Cathepsin B is associated with many tumor progression, including breast cancer [12], lung cancer [13] and pancreatic cancer [14].…”

Section: Introductionmentioning

confidence: 99%

The causal relationship between cathepsins and hepatocellular carcinoma risk: A Mendelian randomization study

Yang,

Mao,

et al. 2024

Preprint

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Background Abnormal expression of cathepsins has been reported in patients with hepatocellular carcinoma (HCC). However, the evidence about the causal role of cathepsins in facilitating or preventing HCC is lacking. Systematically studying the causality between cathepsins and HCC would help provide novel targets for screening and prevention of HCC. Methods We conducted twosample Mendelian randomization (MR) analyses. The data of cathepsins and HCC for analysis were derived from publicly available genetic summary data. The causal effects were estimated with inverse variance weighted, MR-Egger and weighted median. Sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO and leave-one-out analysis. Results The results of univariate MR analysis show that elevated cathepsin S levels increase the risk of HCC. On the other hand, reverse MR analyses indicate that HCC may raise cathepsin Z levels. According to the results of multivariable analysis using nine cathepsin variables, an increased risk of HCC is associated with elevated levels of cathepsin S. Conclusion The evidence that cathepsin S is associated with HCC in a causal way provides a novel insight into the underlying mechanisms of HCC by integrating genomics with cathepsins, and has an implication for HCC screening and prevention.

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Cathepsin K: A Versatile Potential Biomarker and Therapeutic Target for Various Cancers

Cited by 25 publications

References 183 publications

Proteomics study of primary and recurrent adamantinomatous craniopharyngiomas

Proteomics study of primary and recurrent adamantinomatous craniopharyngiomas

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

The causal relationship between cathepsins and hepatocellular carcinoma risk: A Mendelian randomization study

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