Diagnostic, Prognostic, and Immunological Roles of HELLS in Pan-Cancer: A Bioinformatics Analysis

Liang, Xiao; Li, Linji; Yang, Fan

doi:10.3389/fimmu.2022.870726

Cited by 4 publications

(3 citation statements)

References 67 publications

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“…However, it has also been pointed out that genes are aberrantly expressed in speci c subtypes of cancer, and the results may not be re ected in the overall patients of that cancer. Thus, differences in gene expression do not affect cancer survival in certain cancers, whereas its varied expression in different molecular or immune subtypes might play different roles in the prognosis of various cancers [23]. Genetic mutations could induce abnormal gene expression and tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer analysis of UDP-glucose 6-dehydrogenase and its carcinogenesis in hepatocellular carcinoma

Cao,

Li,

Xue

et al. 2024

Preprint

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Backgrounds: Abnormalities in glycometabolism lead to carcinogenesis. UDP-glucose 6-dehydrogenase (UGDH) is the key enzyme of glucuronic acid metabolism and acts as a key mediator in several cancer developmental signaling pathways. In this study, our objective is to offer a more systematic and comprehensive elucidation of the involvement of UGDH in the onset and advancement of various malignancies via an in-depth analysis of UGDH in cancer contexts. Method: We investigated the role of UGDH in cancers using the Human Protein Atlas (HPA), The Cancer Genome Atlas (TCGA), and Genotype-Tissue Expression (GTEx) databases. And analyzed data using various R packages and websites, including TISIDB, cBioPortal, STRING, Cytoscape, GSCALite, and CancerSEA. A rat hepatocellular carcinoma (HCC) model was established using intraperitoneal injection of diethylnitrosamine. Hematoxylin-Eosin (HE) staining, MASSON staining, and KI67 immunohistochemistry of liver tissues were performed. Real-time quantitative PCR (qRT-PCR) and western blotting (WB) were used to detect the expression of UGDH. UGDH gene was knocked down in Huh7 cells, and CCK8 and nude mice tumor xenograft assays were further performed. Results: UGDH high expression is associated with poor clinical outcomes in hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, and sarcoma. And differentially expressed across molecular and immune subtypes. UGDH was primarily involved in the pentose and glucuronate interconversion pathway. Its expression positively correlated with T helper, Tcm, and Th2 cells in most cancers. Moreover, experimental results demonstrated that UGDH expression is elevated in liver cancer and promotes the proliferation of HCC. Conclusions: Our study elucidates that UGDH could be used as a valuable prognostic biomarker and potential therapeutic target in many cancers, especially liver and lung cancer. UGDH could promote the proliferation of HCC cells, possibly by modulating the pentose and glucuronate interconversion pathway.

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Section: Discussionmentioning

confidence: 99%

Pan-cancer analysis of UDP-glucose 6-dehydrogenase and its carcinogenesis in hepatocellular carcinoma

Cao,

Li,

Xue

et al. 2024

Preprint

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“…HELLS is an important component of the chrome remolding complex that helps repair DNA through various mechanisms such as DNA methylation, histone posttranslational modi cation, and nuclear remolding [26]. Its expression is positively correlated with Th2 and Tcm cells in most cancers [27]. ARL1 is mainly related to oxidative damage.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic and proteomic analysis of the mechanisms underlying the role of the CCT3 gene in breast cancer

Wang

et al. 2023

Preprint

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Background Breast cancer has surpassed lung cancer as the most common cancer in the world. Our previous research showed that silencing the expression of the CCT3 gene significantly decreased the proliferation and metastasis of breast cancer cells, but the mechanism is still unclear. In this study, we investigated CCT3 gene and protein expression by transcriptomics and proteomics to explore the mechanism underlying its function. Methods MDA-MB-231 cells were transfected with CCT3-siRNA to knock down the expression of the CCT3 gene. qRT‒PCR was used to measure the efficiency of the suppression. We used RNA-seq and tandem mass tag proteomics analysis to identify differentially expressed genes and proteins, respectively. The possible biological consequences were determined by bioinformatics analysis. Results The mRNA expression of CCT3 decreased by 87.6% in MDA-MB-231 cells transfected with shCCT3 lentivirus. RNA-seq identified 449 differentially expressed genes after transfection with shCCT3, including 240 upregulated genes and 209 downregulated genes, and 61 differentially expressed proteins (33 upregulated and 28 downregulated) were identified by TMT proteomics analysis. GO and KEGG enrichment revealed the biological and molecular functions in CCT3-knockdown cells. Conjoint analysis revealed the expression of several genes and proteins, such as RPUSD4, LUC7L3, HELLS, ARL1, and SPINT2. Conclusions We explored the molecular mechanism by which the proliferation and metastasis of breast cancer cells are promoted after the expression of CCT3 is inhibited through transcriptomics and proteomics, and we initially identified several key genes and proteins. The functional verification of these genes requires further research.

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“…We utilized the Human Protein Atlas (HPA) database ( https://www.proteinatlas.org/ ), an open-source database containing information on human proteins discovered in normal and cancer tissues ( 19 ). In our study, we employed the protein expression module of HPA to examine the protein levels of APOA1 in normal gastric tissue and GC tissue.…”

Section: Methodsmentioning

confidence: 99%

APOA1 mRNA and serum APOA1 protein as diagnostic and prognostic biomarkers in gastric cancer

Li,

Han,

Gao

et al. 2024

Transl Cancer Res

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Background Gastric cancer (GC) remains a formidable challenge in oncology, ranking as a leading cause of cancer mortality globally. This underscores an urgent need for innovative prognostic markers that can revolutionize patient management and outcomes. Recent insights into cancer biology have spotlighted the profound influence of lipid metabolism alterations on tumorigenesis, tumor progression, and the tumor microenvironment. These alterations not only fuel cancer cell growth and proliferation but also play a strategic role in evading immune surveillance and promoting metastasis. The intricate web of lipid metabolism in cancer cells, characterized by deregulated uptake, synthesis, and oxidation of fatty acids (FAs), opens new avenues for targeted therapeutic interventions and prognostic evaluations. Specifically, this study zeroes in on apolipoprotein A-I ( APOA1 ), a key player in lipid metabolism, to unearth its prognostic value in GC. By delving into the role of lipid metabolism-related genes, particularly APOA1 , we aim to unveil their potential as groundbreaking biomarkers for GC prognosis. This endeavor not only aims to enhance our understanding of the molecular underpinnings of GC but also to spearhead the development of lipid metabolism-based strategies for improved diagnostic, prognostic, and therapeutic outcomes. Methods Transcriptomic and clinical data from GC patients and healthy individuals were sourced from The Cancer Genome Atlas (TCGA) database, a comprehensive project that molecularly characterizes over 20,000 primary cancer and matched normal samples across 33 cancer types. Significantly differentially expressed lipid metabolism-related genes were identified using the “limma” package in R. Prognostic genes were selected via univariate Cox regression analysis. Differential gene enrichment analysis was performed using Metascape ( http://www.metascape.org ). The Human Protein Atlas (HPA, https://www.proteinatlas.org ) provided information on APOA1 protein expression in GC and healthy tissues. Immune cell infiltration was analyzed using the CIBERSORT algorithm ( http://cibersort.stanford.edu ). Results Significant differences in lipid metabolism-related gene expression were observed between GC and normal tissues, closely linked to FA metabolism, oxidoreductase activity, and sphingolipid metabolism. APOA1 emerged as a potential prognostic biomarker by intersecting prognostic and differentially expressed lipid metabolism genes. Immunohistochemical analysis confirmed APOA1 downregulation in GC. The receiver operating characteristic (ROC) analysis demonstrated its predictive value, with the area under the curve (AUC) being 0.64 [95% confidence interval (CI): 0.52–0.76]. APOA1 expression correlated with immune cell ...

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Diagnostic, Prognostic, and Immunological Roles of HELLS in Pan-Cancer: A Bioinformatics Analysis

Cited by 4 publications

References 67 publications

Pan-cancer analysis of UDP-glucose 6-dehydrogenase and its carcinogenesis in hepatocellular carcinoma

Pan-cancer analysis of UDP-glucose 6-dehydrogenase and its carcinogenesis in hepatocellular carcinoma

Transcriptomic and proteomic analysis of the mechanisms underlying the role of the CCT3 gene in breast cancer

APOA1 mRNA and serum APOA1 protein as diagnostic and prognostic biomarkers in gastric cancer

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