Downregulation of CLCA4 expression is associated with the development and progression of colorectal cancer

Wei, Lihui; Chen, Wujin; Zhao, Jinyan; Fang, Yi; Lin, Jiumao

doi:10.3892/ol.2020.11640

Cited by 8 publications

(5 citation statements)

References 30 publications

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“…Similar to our results, Hou et al confirmed that CLCA4 was at a low level in bladder cancer [21]. Moreover, CLCA4 was reduced in colorectal cancer, and CLCA4 expression was associated with the overall survival rate of patients with breast cancer, stomach cancer, colorectal cancer, and head and neck cancer [22].…”

Section: Discussionsupporting

confidence: 92%

Expression of the CLCA4 Gene in Esophageal Carcinoma and Its Impact on the Biologic Function of Esophageal Carcinoma Cells

Song

Zhang

et al. 2021

Journal of Oncology

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Background. Esophageal carcinoma (ESCA) is one of the malignant tumors with a high mortality rate worldwide, which seriously affects people’s health. Calcium-activated chloride channel 4 (CLCA4) was reported to be a tumor inhibitor in hepatocellular carcinoma. Nevertheless, the role of CLCA4 in ESCA is still unclear. Methods. RT-qPCR and western blot assay were used to test the expression pattern of CLCA4 in ESCA tissues and cells. CCK-8 assay was performed to detect the effect of CLCA4 overexpression on cell proliferation in ESCA cells. Transwell assay was used to measure the effect of CLCA4 upregulation on migration and invasion abilities of ESCA cells. Animal experiments were conducted to investigate the role of CLCA4 upregulation in tumor growth in vivo. Results. CLCA4 was significantly reduced in ESCA tissues and correlated with T stage, differentiation, and lymph node metastasis. CLCA4 overexpression was found to inhibit cell proliferation, migration, invasion, and EMT progression in ESCA cells. Moreover, CLCA4 overexpression suppressed tumor growth in vivo. Conclusion. CLCA4 was suggested to act as a tumor inhibitor in ESCA and might be a therapeutic target gene for the treatment of patients with ESCA.

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Section: Discussionsupporting

confidence: 92%

Expression of the CLCA4 Gene in Esophageal Carcinoma and Its Impact on the Biologic Function of Esophageal Carcinoma Cells

Song

Zhang

et al. 2021

Journal of Oncology

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“…However, in another study, high SPINK1 expression was associated with a good prognosis in patients with advanced colorectal cancer receiving targeted cetuximab-based therapy ( 58 ). Calcium-activated chloride channel (CLCA) modulators are involved in many biological processes, including apoptosis, airway inflammation, and immune regulation ( 59 , 60 ). Wei et al analyzed CLCA4 expression in colorectal normal, adenoma, and cancer tissues based on immunohistochemical tissue microarrays and found a gradual decrease in tumor progression ( 60 ).…”

Section: Discussionmentioning

confidence: 99%

“…Calcium-activated chloride channel (CLCA) modulators are involved in many biological processes, including apoptosis, airway inflammation, and immune regulation ( 59 , 60 ). Wei et al analyzed CLCA4 expression in colorectal normal, adenoma, and cancer tissues based on immunohistochemical tissue microarrays and found a gradual decrease in tumor progression ( 60 ). In addition, low CLCA4 expression was associated with overall survival in patients with various tumors, including CC, head and neck cancer, gastric cancer, and breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of Necroptosis-Related Genes for Prognosis, Immune Microenvironment Infiltration, and Drug Sensitivity in Colon Cancer

Zhang

et al. 2022

Front. Med.

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BackgroundNecroptosis, is intimately linked to tumor development and prognosis and has been considered as a target for anticancer therapy. However, the role of necroptosis-related genes (NRGs) in colon cancer is unclear.MethodsIn the present study, we screened 76 NRGs from previous studies and described the landscape of transcriptomic and genetic variation of NRGs in colon cancer (CC) patient samples. Molecular subtypes of necroptosis in colon cancer were identified by clustering analysis, and these molecular subtypes were linked to patient prognosis and TME cell infiltration characteristics. Then, the NRS-score for predicting overall survival (OS) was built based on the TCGA database and validated in the GSE39582 cohort for its predictive power in CC patients. Besides, the ESTIMATE and CIBERSORT algorithms were applied to explore the relationship between NRS-score and tumor immune microenvironment.ResultsWe identified two molecular subtypes associated with necroptosis in CC, which have diverse prognosis and immune microenvironment characteristics. Based on the differentially expressed genes between the two molecular subtypes, we further developed a necroptosis risk score signature, referred to as NRS-score. High NRS-score was associated with poor prognosis in CC through immunosuppressive microenvironment and immune escape mechanisms. The nomogram based on NRS-score showed excellent ability to predict prognosis. In addition, NRS-score presented a positive correlation with tumor mutational burden (TMB) and immune checkpoint blockade (ICB) expression and was closely correlated with multiple anticancer agent susceptibility.ConclusionThis work revealed a close relationship between necroptosis and the prognosis and immune microenvironment of colon cancer. The NRS-score based on the 8-gene signature may be used to predict the sensitivity of immunotherapy and chemotherapy in colon cancer patients, and provides a foundation for future studies targeting necroptosis and its immune microenvironment.

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“…CLCA4 is a tumor suppressor and a member of the calcium-activated chloride channel protein family, which is associated with the growth, proliferation, migration, and invasion of tumor cells. A study has shown decreased expression of CLCA4 in colon cancer, which was associated with the development and progression of colon cancer (28). Mo et al showed that 11.8% of patients with CRC have high microsatellite instability and harbor CLCA4 frameshift mutations in repeat sequences (29).…”

Section: Discussionmentioning

confidence: 99%

A novel enterocyte-related 4-gene signature for predicting prognosis in colon adenocarcinoma

Cheng

Wei²,

et al. 2022

Front. Immunol.

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BackgroundColon adenocarcinoma (COAD) is a fatal disease, and its cases are constantly increasing worldwide. Further, the therapeutic and management strategies for patients with COAD are still unsatisfactory due to the lack of accurate patient classification and prognostic models. Therefore, our study aims to identify prognostic markers in patients with COAD and construct a cell subtype-specific prognostic model with high accuracy and robustness.MethodsSingle-cell transcriptomic data of six samples were retrieved from the Gene expression omnibus (GEO) database. The cluster annotation and cell-cell communication analysis identified enterocytes as a key player mediating signal communication networks. A four-gene signature prognostic model was constructed based on the enterocyte-related differentially expressed genes (ERDEGs) in patients with COAD of the Cancer Genome Atlas cohort. The prognostic model was validated on three external validation cohorts from the GEO database. The correlation between immune cell infiltration, immunotherapy response, drug sensitivity, and the four-gene signature prognostic model was investigated. Finally, immunohistochemistry (IHC) was performed to determine the expression of the four genes.ResultsWe found that the proportion of epithelial cells was obviously large in COAD samples. Further analysis of epithelial cells showed that the activity of the enterocytes was highest in the cell-cell communication network. Based on enterocyte data, 30 ERDEGs were identified and a 4-gene prognostic model including CPM, CLCA4, ELOVL6, and ATP2A3 was developed and validated. The risk score derived from this model was considered as an independent variable factor to predict overall survival. The patients were divided into high- and low-risk groups based on the median riskscore value. The correlation between immune cell infiltration, immunotherapy response, immune status, clinical characteristics, drug sensitivity, and risk score was analyzed. IHC confirmed the expression of signature genes in tissues from normal individuals, patients with polyps, and COAD.ConclusionIn this study, we constructed and validated a novel four-gene signature prognostic model, which could effectively predict the response to immunotherapy and overall survival in patients with COAD. More importantly, this model provides useful insight into the management of colon cancer patients and aids in designing personalized therapy.

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Downregulation of CLCA4 expression is associated with the development and progression of colorectal cancer

Cited by 8 publications

References 30 publications

Expression of the CLCA4 Gene in Esophageal Carcinoma and Its Impact on the Biologic Function of Esophageal Carcinoma Cells

Expression of the CLCA4 Gene in Esophageal Carcinoma and Its Impact on the Biologic Function of Esophageal Carcinoma Cells

Integrated Analysis of Necroptosis-Related Genes for Prognosis, Immune Microenvironment Infiltration, and Drug Sensitivity in Colon Cancer

A novel enterocyte-related 4-gene signature for predicting prognosis in colon adenocarcinoma

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