Cathepsin&amp;nbsp;B is highly expressed in pancreatic cancer stem‑like cells and is associated with patients' surgical outcomes

Fujimoto, Takuya; Tsunedomi, Ryouichi; Matsukuma, Satoshi; Yoshimura, Kiyoshi; Oga, Atsunori; Fujiwara, Norio; Fujiwara, Yasuhiro; Matsui, Hiroto; Shindo, Yoshitaro; Tokumitsu, Yukio; Suzuki, Nobuaki; Kobayashi, Shogo; Hazama, Shoichi; Eguchi, Hidetoshi; Nagano, Hiroaki

doi:10.3892/ol.2020.12291

Cited by 13 publications

(9 citation statements)

References 45 publications

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“…In terms of pathological processes, CTSB related to arthritis and atherosclerotic vascular diseases 17 , and has also been confirmed to be involved in inflammatory brain diseases and brain aging 21 , memory and psychiatric disorders and neuronal cascade death response after cerebral infarction 22 . CTSB has been regarded as an important biomarker and potential therapeutic target for many cancers 15 , such as pancreatic cancer 23 , gastric cancer 24 , colon cancer 25 , breast cancer 8 , acute myelogenous leukemia 26 , oral squamous cell carcinoma and thyroid cancer 27 . Recent studies have confirmed that CTSB is rarely expressed in normal brain tissues but overexpressed in glioblastoma (GBM) and glioblastoma stem cells (GSCs) 28 , 29 .…”

Section: Introductionmentioning

confidence: 99%

CTSB is a negative prognostic biomarker and therapeutic target associated with immune cells infiltration and immunosuppression in gliomas

Chen

Liu

et al. 2022

Sci Rep

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Previous researches have demonstrated the meaning of CTSB for the progress of several tumors, whereas few clues about its immunological characteristic in gliomas. Here we systematically explored its biologic features and clinical significance for gliomas. 699 glioma cases of TCGA and 325 glioma cases of CGGA were respectively included as training and validating cohorts. R software was used for data analysis and mapping. We found that CTSB was remarkably highly-expressed for HGG, IDH wild type, 1p19q non-codeletion type, MGMT promoter unmethylation type and mesenchymal gliomas. CTSB could specifically and sensitively indicate mesenchymal glioma. Upregulated CTSB was an independent hazard correlated with poor survival. CTSB-related biological processes in gliomas chiefly concentrated on immunoreaction and inflammation response. Then we proved that CTSB positively related to most inflammatory metagenes except IgG, including HCK, LCK, MHC II, STAT1 and IFN. More importantly, the levels of glioma-infiltrating immune cells were positively associated with the expression of CTSB, especially for TAMs, MDSCs and Tregs. In conclusion, CTSB is closely related to the malignant pathological subtypes, worse prognosis, immune cells infiltration and immunosuppression of gliomas, which make it a promising biomarker and potential target in the diagnosis, treatment and prognostic assessment of gliomas.

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Section: Introductionmentioning

confidence: 99%

CTSB is a negative prognostic biomarker and therapeutic target associated with immune cells infiltration and immunosuppression in gliomas

Chen

Liu

et al. 2022

Sci Rep

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“…It was shown to play an important part in the process of pancreatic carcinogenesis, including cancer-related angiogenesis, malignant invasion, and cancer metastasis ( 30 , 33 , 38 , 40 ). Researchers have identified high expression of CTSB in human pancreatic ductal adenocarcinomas and pancreatic cancer stem cells, and demonstrated its association with poor survival and surgical outcomes ( 44 , 45 ). CTSB exhibits optimal activity in a slightly acidic pH ( 46 , 47 ).…”

Section: Discussionmentioning

confidence: 99%

Bibliometric Analysis of Cathepsin B Research From 2011 to 2021

et al. 2022

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Cathepsin B (CTSB) is a lysosomal protease implicated in the progression of various diseases. A large number of CTSB-related studies have been conducted to date. However, there is no comprehensive bibliometric analysis on this subject. In our study, we performed quantitative analysis of CTSB-related publications retrieved from the Science Citation Index Expanded (SCIE) of the Web of Science Core Collection (reference period: 2011–2021). A total of 3,062 original articles and reviews were retrieved. The largest number of publications were from USA (n = 847, 27.66%). The research output of each country showed positive correlation with gross domestic product (GDP) (r = 0.9745, P < 0.0001). Active collaborations between countries/regions were also observed. Reinheckel T and Sloane BF were perhaps the most impactful researchers in the research landscape of CTSB. Plos ONE was the most prevalent (119/3,062, 3.89%) and cited journal (3,021 citations). Comprehensive analysis of the top citations, co-citations, and keywords was performed to acquire the theoretical basis and hotspots of CTSB-related research. The main topics included CTSB-related cancers and inflammatory diseases, CTSB-associated cell death pattern, and the applications of CTSB. These results provide comprehensive insights into the current status of global CTSB-related research especially in pancreas, which is worthy of continued follow-up by practitioners and clinicians in this field.

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“…In the past few years, the role of various classes of cathepsins in the proliferation and metastasis of various types of human cancers has been extensively studied. The overexpression of cathepsin B promotes invasion and metastasis of breast cancer, pancreatic cancer, HCC, and colorectal cancer [11][12][13][14] . In addition, cathepsin B has been found to be involved in tumor initiation, migration, and drug resistance of glioblastoma stem cells and prostate cancer stem cells 41,42 .…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have found that the overexpression of cathepsin B leads to the invasiveness and metastasis of breast cancer, pancreatic cancer, HCC, and colorectal cancer, by activating the ErbB oncogenic signaling pathway [11][12][13][14] . The cytosol concentration of cathepsin D was found to have a strong in uence on metastasis in breast cancer 15,16 .…”

Section: Introductionmentioning

confidence: 99%

Prognostic Significance and Oncogene Function of Cathepsin A in Hepatocellular Carcinoma

Wang

Xu²,

Yang³

et al. 2021

Preprint

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Cathepsin A (CTSA) is a lysosomal protease that regulates galactoside metabolism. The previous study has shown CTSA is abnormally expressed in various types of cancer. However, rarely the previous study has addressed the role of CTSA in hepatocellular carcinoma (HCC) and its prognostic value. To study the clinical value and potential function of CTSA in HCC, datasets from the Cancer Genome Atlas (TCGA) database and a 136 HCC patient cohort were analyzed. CTSA expression was found to be significantly higher in HCC patients compared with normal liver tissues, which was supported by immunohistochemistry (IHC) validation. Both gene ontology (GO) and The Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated that CTSA co-expressed genes were involved in ATP hydrolysis coupled proton transport, carbohydrate metabolic process, lysosome organization, oxidative phosphorylation, other glycan degradation, etc. Survival analysis showed a significant reduction both in overall survival (OS) and recurrence-free survival (RFS) of patients with high CTSA expression from both the TCGA HCC cohort and 136 patients with the HCC cohort. Furthermore, CTSA overexpression has diagnostic value in distinguishing between HCC and normal liver tissue (Area under curve (AUC) = 0.864). Moreover, Gene set enrichment analysis (GSEA) showed that CTSA expression correlated with the oxidative phosphorylation, proteasome, and lysosome, etc. in HCC tissues. These findings demonstrate that CTSA may as a potential diagnostic and prognostic biomarker in HCC.

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Cathepsin B is highly expressed in pancreatic cancer stem‑like cells and is associated with patients' surgical outcomes

Cited by 13 publications

References 45 publications

CTSB is a negative prognostic biomarker and therapeutic target associated with immune cells infiltration and immunosuppression in gliomas

CTSB is a negative prognostic biomarker and therapeutic target associated with immune cells infiltration and immunosuppression in gliomas

Bibliometric Analysis of Cathepsin B Research From 2011 to 2021

Prognostic Significance and Oncogene Function of Cathepsin A in Hepatocellular Carcinoma

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