The multiple roles and therapeutic potential of clusterin in non-small-cell lung cancer: a narrative review

Tan, Juofang; Guo, Wei; Yang, Sheng; Han, Dingpei; Li, Hecheng

doi:10.21037/tlcr-20-1298

Cited by 13 publications

(13 citation statements)

References 119 publications

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“…CLU is also considered to be a promising biomarker for cell death, malignancy, cancer progression and drug resistance development (31). CLU plays an important carcinogenic role by promoting various downstream carcinogenic pathways (11,(32)(33)(34). Protein kinase D3 is a key regulator of CLU and promoted tumor growth in triple-negative breast cancer (35).…”

Section: Discussionmentioning

confidence: 99%

“…Clusterin (CLU) is an evolutionarily conserved molecular chaperone present in diverse human tissues and fluids, and is considered an important tumor regulator (9)(10)(11). CLU regulates several cancer-related cellular events, including cancer cell proliferation, metastasis, stemness, epithelialmesenchymal transition, survival, therapeutic resistance, and suppression of programmed cell death to support tumor growth and recurrence (12)(13)(14).…”

Section: Original Articlementioning

confidence: 99%

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Clusterin is a biomarker of breast cancer prognosis and correlated with immune microenvironment

Yang¹,

Yang²,

Dong³

et al. 2023

Transl Cancer Res

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Background: It has been established that clusterin is involved in the invasion of immune cells in the tumor microenvironment, but it remains unknown how it promotes immune invasion in breast cancer. Methods:We used Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to assess the relation between expression of clusterin and immunoinfiltration-related marker genes. TIMER database was used to evaluate the expression of clusterin, and its relation to tumor immune invasion was examined. Based on Kaplan-Meier plotter database, we investigated the association between clusterin expression and prognosis in patients with cancer, and the impact of clinicopathological factors and cancer-related outcomes.Results: Clusterin expression was markedly associated with prognosis of a variety of tumors, specifically breast cancer. Enhanced clusterin expression was markedly associated with molecular typing of breast cancer and expression of multiple markers related to specific immune cell subsets.Conclusions: These results indicate that clusterin is connected to prognosis of breast cancer patients and tumor immune cell infiltration. This demonstrates that clusterin may be a biomarker of immune cell recruitment into breast tumors and an important biomarker for immune cell infiltration; consequently being a valuable prognostic factor in breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

Section: Original Articlementioning

confidence: 99%

Clusterin is a biomarker of breast cancer prognosis and correlated with immune microenvironment

Yang¹,

Yang²,

Dong³

et al. 2023

Transl Cancer Res

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“…CLU gene expression has been linked to an elevated risk of lung cancer ( Chen et al, 2020 ; Tan et al, 2021 ; Yuan et al, 2021 ). Nevertheless, in the TCGA-LUAD/LUSC cohort, we could not examine the correlation between CLU expression and the survival prognosis of lung cancer patients, which might be due to various data processing or revised survival information.…”

Section: Discussionmentioning

confidence: 99%

A pan-cancer analysis reveals role of clusterin (CLU) in carcinogenesis and prognosis of human tumors

Cui

et al. 2023

Front. Genet.

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Clusterin (CLU) is a chaperone-like protein that has been demonstrated to have a direct relationship with cancer occurrence, progression, or metastasis. Clusterin was downregulated in tumor tissues using three datasets of tongue squamous carcinoma from the Gene Expression Omnibus. We further retrieved datasets from The Cancer Genome Atlas and Gene Expression Omnibus to thoroughly investigate the carcinogenic consequences of Clusterin. Our findings revealed that decreased Clusterin expression in malignancies was associated with a worse overall survival prognosis in individuals with multiple tumors; Clusterin gene deep deletions were found in almost all malignancies and were connected to most cancer patient’s prognosis, Clusterin DNA methylation level was dependent on tumor type, Clusterin expression was also linked to the invasion of cancer-associated CD8+ T-cells and fibroblasts in numerous cancer forms. Moreover, pathway enrichment analysis revealed that Clusterin primarily regulates biological processes such as cholesterol metabolism, phospholipid binding, and protein-lipid complex formation. Overall, our pan-cancer research suggests that Clusterin expression levels are linked to tumor carcinogenesis and prognosis, which contributes to understanding the probable mechanism of Clusterin in tumorigenesis as well as its clinical prognostic significance.

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“…Another subtype is nuclear cluster protein (nCLU), which exists in the nucleus. The third subtype is cytoplasmic aggregation protein (cCLU), which mainly exists in the cytoplasm and is still little known [ 33 ]. We found that CLU was abundant in serum but not in exosomes, and that CLU expression in lung adenocarcinomas was lower than that in adjacent tissues.…”

Section: Discussionmentioning

confidence: 99%

Serum exosomal proteomics analysis of lung adenocarcinoma to discover new tumor markers

Liu

Tian

et al. 2022

BMC Cancer

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Background Among the most aggressive and rapidly lethal types of lung cancer, lung adenocarcinoma is the most common type. Exosomes, as a hot area, play an influential role in cancer. By using proteomics analysis, we aimed to identify potential markers of lung adenocarcinoma in serum. Methods In our study, we used the ultracentrifugation method to isolate serum exosomes. The Liquid chromatography-mass spectrometry (LC–MS) and bioinformatics analysis were used to identify potential serum exosomal proteins with altered expression among patients with advanced lung adenocarcinoma, early lung adenocarcinoma, and healthy controls. A western blot (WB) was performed to confirm the above differential expression levels in a separate serum sample-isolated exosome, and immunohistochemistry (IHC) staining was conducted to detect expression levels of the above differential proteins of serum exosomes in lung adenocarcinoma tissues and adjacent tissues. Furthermore, we compared different expression models of the above differential proteins in serum and exosomes. Result According to the ITGAM (Integrin alpha M chain) and CLU (Clusterin) were differentially expressed in serum exosomes among different groups as well as tumor tissues and adjacent tissues. ITGAM was significantly and specifically enriched in exosomes. As compared to serum, CLU did not appear to be significantly enriched in exosomes. ITGAM and CLU were identified as serum exosomal protein markers of lung adenocarcinoma. Conclusions This study can provide novel ideas and a research basis for targeting lung adenocarcinoma treatment as a preliminary study.

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The multiple roles and therapeutic potential of clusterin in non-small-cell lung cancer: a narrative review

Cited by 13 publications

References 119 publications

Clusterin is a biomarker of breast cancer prognosis and correlated with immune microenvironment

Clusterin is a biomarker of breast cancer prognosis and correlated with immune microenvironment

A pan-cancer analysis reveals role of clusterin (CLU) in carcinogenesis and prognosis of human tumors

Serum exosomal proteomics analysis of lung adenocarcinoma to discover new tumor markers

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