Prognostic model development and clinical correlation of eight key genes in skin cutaneous melanoma

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Abstract

Cutaneous melanoma (SKCM) is a challenging and increasingly prevalent cancer with limited effective treatments. In our extensive study of 342 SKCM samples, we developed a prognostic model identifying eight key genes—CASPASE7CLEAVEDD198, FOXO3A, Melanoma gp100, CD171, 1433ZETA, SRC, P21, and CABL—linked to SKCM prognosis. Statistical analysis indicated significant differences in clinical outcomes between low and high-risk groups, corroborated by principal component analysis (PCA). Survival analysis and receiver operating characteristic (ROC) curve analysis confirmed the model's predictive accuracy for SKCM prognosis. Additionally, we observed notable correlations between the expression levels of genes related to prognosis and clinical characteristics. Our research offers crucial insights into SKCM prognosis, suggesting potential diagnostic markers and personalized treatment targets.

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Cuproptosis-related lncRNA predict prognosis and immune response of lung adenocarcinoma

Fangwei Wang, Hongsheng Lin, Qisheng Su … (2022)

Background Lung adenocarcinoma (LUAD) accounts for 50% of lung cancers, with high mortality and poor prognosis. Long non-coding RNA (lncRNA) plays a vital role in the progression of tumors. Cuproptosis is a newly discovered form of cell death that is highly investigated. Therefore, in the present study, we aimed to investigate the role of cuproptosis-related lncRNA signature in clinical prognosis prediction and immunotherapy and the relationship with drug sensitivity. Material and methods Genomic and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and cuproptosis-related genes were obtained from cuproptosis-related studies. The prognostic signature was constructed by co-expression analysis and Cox regression analysis. Patients were divided into high and low risk groups, and then, a further series of model validations were carried out to assess the prognostic value of the signature. Subsequently, lncRNAs were analyzed for gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes Enrichment (KEGG), immune-related functions, and tumor mutation burden (TMB). Finally, we used tumor immune dysfunction and exclusion (TIDE) algorithms on immune escape and immunotherapy of cuproptosis-related lncRNAs, thereby identifying its sensitivity toward potential drugs for LUAD. Results A total of 16 cuproptosis-related lncRNAs were obtained, and a prognostic signature was developed. We found that high-risk patients had worse overall survival (OS) and progression-free survival (PFS) and higher mortality. Independent prognostic analyses, ROC, C-index, and nomogram showed that the cuproptosis-related lncRNAs can accurately predict the prognosis of patients. The nomogram and heatmap showed a distinct distribution of the high- and low-risk cuproptosis-related lncRNAs. Enrichment analysis showed that the biological functions of lncRNAs are associated with tumor development. We also found that immune-related functions, such as antiviral activity, were suppressed in high-risk patients who had mutations in oncogenes. OS was poorer in patients with high TMB. TIDE algorithms showed that high-risk patients have a greater potential for immune escape and less effective immunotherapy. Conclusion To conclude, the 16 cuproptosis-related lncRNAs can accurately predict the prognosis of patients with LUAD and may provide new insights into clinical applications and immunotherapy.

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Genetic inactivation or pharmacological inhibition of Pdk1 delays development and inhibits metastasis of BrafV600E::Pten−/− melanoma

Marzia Scortegagna, Chelsea Ruller, Yongmei Feng … (2013)

Phosphoinositide-dependent kinase-1 (PDK-1) is a serine/threonine protein kinase that phosphorylates members of the conserved AGC kinase superfamily, including AKT and PKC, and is implicated in important cellular processes including survival, metabolism and tumorigenesis. In large cohorts of nevi and melanoma samples, PDK1 expression was significantly higher in primary melanoma, compared with nevi, and was further increased in metastatic melanoma. PDK1 expression suffices for its activity, due to auto-activation, or elevated phosphorylation by phosphoinositide 3'-OH-kinase (PI 3-K). Selective inactivation of Pdk1 in the melanocytes of BrafV600E::Pten−/− or BrafV600E::Cdkn2a−/−::Pten−/− mice delayed the development of pigmented lesions and melanoma induced by systemic or local administration of 4-HT. Melanoma invasion and metastasis were significantly reduced or completely prevented by Pdk1 deletion. Administration of the PDK1 inhibitor GSK2334470 (PDKi) effectively delayed melanomagenesis and metastasis in BrafV600E::Pten−/− mice. Pdk1−/− melanomas exhibit a marked decrease in the activity of AKT, P70S6K and PKC. Notably, PDKi was as effective in inhibiting AGC kinases and colony forming efficiency of melanoma with Pten WT genotypes. Gene expression analyses identified Pdk1-dependent changes in FOXO3a-regulated genes and inhibition of FOXO3a restored proliferation and colony formation of Pdk1−/− melanoma cells. Our studies provide direct genetic evidence for the importance of PDK1, in part through FOXO3a-dependent pathway, in melanoma development and progression.

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Toll-like receptor 5 (TLR5) expression is a novel predictive marker for recurrence and survival in squamous cell carcinoma of the tongue

J Kauppila, A Mattila, T J Karttunen … (2013)

Background: Toll-like receptor 5 (TLR5) is an immune receptor recognising bacterial flagellin. Activation of TLR5 results in cancer invasion and cytokine release. As certain bacteria have been linked to oral cancer, we wanted to study TLR5 expression in oral tongue squamous cell carcinoma (OTSCC). Methods: Samples from 119 patients with OTSCC were obtained, including 101 samples of adjacent normal lingual mucosa. The TLR5 histoscore (0–300) was assessed semiquantitatively by immunohistochemistry in a blinded manner. Results: Toll-like receptor 5 was expressed in 84 normal epithelia and 118 cancer samples. Expression of TLR5 was increased in cancer when compared with normal lingual epithelium (median histoscore 15 vs 135). In cancer, higher TLR5 was associated with age of >70 years at the time of diagnosis, female gender and disease recurrence. No association between TLR5 expression and tumour grade, stage or treatment was found. In multivariate analysis, TLR5 was an independent predictor of cancer mortality (hazard ratio (HR) 3.587, 95% confidence interval (CI) (1.632–7.882)) and disease recurrence (HR 4.455, 95% CI (2.168–9.158)). Conclusion: Toll-like receptor 5 has a previously undescribed role in the pathophysiology of OTSCC and might represent a link between bacteria and cancer. It could be a useful marker for predicting recurrence or survival of OTSCC patients.

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Author and article information

Contributors

Ling Xie

Journal

Journal ID (nlm-ta): Heliyon

Journal ID (iso-abbrev): Heliyon

Title: Heliyon

Publisher: Elsevier

ISSN (Electronic): 2405-8440

Publication date PMC-release: 01 July 2024

Publication date Collection: 15 July 2024

Publication date (Electronic): 01 July 2024

Volume: 10

Issue: 13

Electronic Location Identifier: e33930

Affiliations

[a ]Dermatology Department, Chengdu Second People's Hospital, No.10 Qingyun South Street, Jinjiang Zone, Chengdu, Sichuan, 610000, China

[b ]Chengdu Badachu Medical Beauty Hospital, 1-5 Floors, No. 688, Middle Section of Tianfu Avenue, Chengdu High Tech Zone, Pilot Free Trade Zone, Sichuan, China

Author notes

[∗ ]Corresponding author 15982896980@ 123456163.com

Article

Publisher Item ID: S2405-8440(24)09961-4 Publisher ID: e33930

DOI: 10.1016/j.heliyon.2024.e33930

PMC ID: 11283098

PubMed ID: 39071565

SO-VID: 0265e161-beae-4655-a925-a697a2fa45f2

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 30 July 2023

Date revision received : 29 June 2024

Date accepted : 30 June 2024

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Prognostic model development and clinical correlation of eight key genes in skin cutaneous melanoma

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Karger: Dermatology

Most cited references 38

Cuproptosis-related lncRNA predict prognosis and immune response of lung adenocarcinoma

Genetic inactivation or pharmacological inhibition of Pdk1 delays development and inhibits metastasis of BrafV600E::Pten−/− melanoma

Toll-like receptor 5 (TLR5) expression is a novel predictive marker for recurrence and survival in squamous cell carcinoma of the tongue

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