Abstract
CLIC5 encoded protein associates with actin-based cytoskeletal and is increasingly thought to play significant roles in human cancers. We use TCGA and GEO to explore CLIC5 expression differences, mutation and DNA methylation, TMB, MSI, and immune cell infiltration. We verified the mRNA expression of CLIC5 in human ovarian cancer cells by real-time PCR and detected the expression of CLIC5 as well as immune marker genes in ovarian cancer by immunohistochemistry. The pan-cancer analysis showed that CLIC5 is highly expressed in several malignant tumors. In some cancers, CLIC5 expression in tumor samples is associated with poorer overall survival. For example, patients with ovarian cancer with high expression of CLIC5 have a poor prognosis. CLIC5 mutation frequency increased in all tumor types. The CLIC5 promoter is hypomethylated in most tumors. CLIC5 was associated with tumor immunity and different immune cells of different tumor types, such as CD8 + T cells, tumor-associated fibroblasts, macrophages, etc. CLIC5 was positively correlated with various immune checkpoints, and TMB and MSI were correlated with dysregulation of CLIC5 in tumors. The expression of CLIC5 in ovarian cancer was detected by qPCR and IHC, and the results were consistent with the bioinformatics results. There were a strong positive correlation between CLIC5 expression and M2 macrophage (CD163) infiltration and a negative correlation with CD8 + T-cell infiltration. In conclusions, our first pan-cancer analysis offered a detailed grasp of the cancerogenic functions of CLIC5 in a variety of malignancies. CLIC5 participated in immunomodulation and performed a crucial function in the tumor microenvironment.
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Data availability
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/supplementary material.
Abbreviations
- ACC:
-
Adrenocortical carcinoma
- BLCA:
-
Bladder urothelial carcinoma
- BRCA:
-
Breast invasive carcinoma
- CLIC5:
-
Chloride intracellular channel protein 5
- CHOL:
-
Cholangiocarcinoma
- COAD:
-
Colon adenocarcinoma
- CESC:
-
Cervical squamous cell carcinoma
- DLBC:
-
Diffuse large B-cell lymphoma
- DSS:
-
Disease-specific survival
- ERM:
-
Ezrin, radixin, and moesin
- ESCA:
-
Esophageal carcinoma
- GTEx:
-
Genotype-tissue expression
- GBM:
-
Glioblastoma multiforme
- GEO:
-
Gene expression omnibus
- GEPIA:
-
Gene expression profiling interactive analysis
- HNSC:
-
Head and neck squamous cell carcinoma
- KICH:
-
Kidney chromophobe
- KIRC:
-
Kidney renal clear cell carcinoma
- KIRP:
-
Kidney renal papillary cell carcinoma;
- LAML:
-
Acute myeloid leukemia
- LGG:
-
Brain lower grade glioma
- LIHC:
-
Liver hepatocellular carcinoma
- LUAD:
-
Lung adenocarcinoma
- LUSC:
-
Lung squamous cell carcinoma
- MSI:
-
Microsatellite instability
- MESO:
-
Mesothelioma
- OS:
-
Overall survival
- OV:
-
Ovarian cancer
- PFI:
-
Progression-free interval
- PRAD:
-
Prostate adenocarcinoma
- PCPG:
-
Pheochromocytoma and paraganglioma
- READ:
-
Rectum adenocarcinoma
- SKCM:
-
Skin cutaneous melanoma
- SARC:
-
Sarcoma
- STAD:
-
Stomach adenocarcinoma
- TCGA:
-
The cancer genome atlas
- TIMER:
-
Tumor immune estimation resource
- THCA:
-
Thyroid carcinoma
- THYM:
-
Thymoma
- TME:
-
Tumor microenvironment
- TMB:
-
Tumor mutation burden
- TPM:
-
Transcripts per million
- UCEC:
-
Uterine corpus endometrial carcinoma.
- UVM:
-
Uveal melanoma
- UCS:
-
Uterine carcinosarcoma
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The authors would like to thank all of the authors listed in this manuscript.
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This work was supported by grants from National Natural Science Foundation of China, the Natural Science Foundation of China (81172537, 81272900, 81772828), and the 2021 Clinical Research Project of the Second Affiliated Hospital of Guangzhou Medical University (2021-LCYJ-03).
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JC and GX designed the study. MH, JH, and HW collected the literature. QL, CH, JC, and QH analyzed the data. QH, WT, and YX drafted the manuscript. YP, GX, and HL modified the manuscript. All authors contributed to the article and approved the submitted version.
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This study was approved by the Clinical Research and Application Ethics Committee, The Second Hospital of Guangzhou Medical University, Guangzhou, China, and written informed consent was obtained from all donors. The survey was conducted in accordance with the principles of the Declaration of Helsinki. In addition, all the datasets were collected from the publishing literature, so all written informed consent was obtained. Consent for publication of all case reports has been obtained from the individual.
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Huang, Q., Lv, Q., Tang, W. et al. A comprehensively prognostic and immunological analysis of chloride intracellular channel protein 5 (CLIC5) in pan-cancer and identification in ovarian cancer. J Cancer Res Clin Oncol 149, 10561–10583 (2023). https://doi.org/10.1007/s00432-023-04927-4
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DOI: https://doi.org/10.1007/s00432-023-04927-4