Dataset Information

Portraying the dark side of endogenous IFN-λ for promoting cancer progression and immunoevasion in pan-cancer.

ABSTRACT:

Background

IFN-λ has been shown to have a dual function in cancer, with its tumor-suppressive roles being well-established. However, the potential existence of a negative ''tumor-promoting'' effect of endogenous IFN-λ is still not fully understood.

Methods

We conducted a comprehensive review and analysis of the perturbation of IFN-λ genes across various cancer types. Correlation coefficients were utilized to examine the relationship between endogenous IFN-λ expression and clinical factors, immune cell infiltration, tumor microenvironment, and response to immunotherapy. Genes working together with IFN-λ were obtained by constructing the correlation-based network related to IFN-λ and the gene interaction network in the KEGG pathway and IFN-λ-related genes obtained from the networks were integrated as candidate markers for the prognosis model. We then applied univariate and multivariate COX regression models to select cancer-specific independent prognostic markers associated with IFN-λ and to investigate risk factors for these genes by survival analysis. Additionally, computational methods were used to analyze the transcriptome, copy number variations, genetic mutations, and methylation of IFN-λ-related patient groups.

Result

Endogenous expression of IFN-λ has been linked to poor prognosis in cancer patients, with the genes IFN-λ2 and IFN-λ3 serving as independent prognostic markers. IFN-λ acts in conjunction with related genes such as STAT1, STAT2, and STAT3 to affect the JAK-STAT signaling pathway, which promotes tumor progression. Abnormalities in IFN-λ genes are associated with changes in immune checkpoints and immune cell infiltration, which in turn affects cancer- and immune-related pathways. While there is increased immune cell infiltration in patients with IFN-λ expression, this does not improve survival prognosis, as T-cell dysfunction and an inflammatory environment are also present. The amplification of IFNL2 and IFNL3 copy number variants drives specific endogenous expression of IFN-λ in patients, and those with this specific expression have been found to have more mutations in the TP53 gene and lower levels of DNA methylation.

Conclusion

Our study integrated multi-omics data to provide a comprehensive insight into the dark side of endogenous IFN-λ, providing a fundamental resource for further discovery and therapeutic exploration in cancer.

SUBMITTER: Wang ZZ

PROVIDER: S-EPMC10494394 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Portraying the dark side of endogenous IFN-λ for promoting cancer progression and immunoevasion in pan-cancer.

Wang Zhen Zhen ZZ Wen Xiao Ling XL Wang Na N Li Xu Hua XH Guo Yu Y Zhu Xu X Fu Shu Heng SH Xiong Fei Fan FF Li Jin J Wang Limei L Gao Xiao Ling XL Wang Hong Jiu HJ

Journal of translational medicine 20230911 1

<h4>Background</h4>IFN-λ has been shown to have a dual function in cancer, with its tumor-suppressive roles being well-established. However, the potential existence of a negative ''tumor-promoting'' effect of endogenous IFN-λ is still not fully understood.<h4>Methods</h4>We conducted a comprehensive review and analysis of the perturbation of IFN-λ genes across various cancer types. Correlation coefficients were utilized to examine the relationship between endogenous IFN-λ expression and clinical ...[more]

PMID: 37697300

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Dataset Information

Portraying the dark side of endogenous IFN-λ for promoting cancer progression and immunoevasion in pan-cancer.

Background

Methods

Result

Conclusion

Publications

Portraying the dark side of endogenous IFN-λ for promoting cancer progression and immunoevasion in pan-cancer.

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