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pmid:35047409

Comprehensive Analysis of Immune Implication and Prognostic Value of IFI44L in Non-Small Cell Lung Cancer.

Yong Zeng · Zhe Zhang · Hongqiang Chen · Jun Fan · Wenbo Yuan · Jingzhi Li · Shimeng Zhou · Wenbin Liu

Frontiers in oncology · 2021 doi:10.3389/fonc.2021.798425

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title
Comprehensive Analysis of Immune Implication and Prognostic Value of IFI44L in Non-Small Cell Lung Cancer.
doi
10.3389/fonc.2021.798425
pmid
35047409
authors array · 8 items
[0]
Yong Zeng
[1]
Zhe Zhang
[2]
Hongqiang Chen
[3]
Jun Fan
[4]
Wenbo Yuan
[5]
Jingzhi Li
[6]
Shimeng Zhou
[7]
Wenbin Liu
journal
Frontiers in oncology
year
2021
abstract
Interferon-induced protein 44-like (IFI44L), a type I interferon-stimulated gene (ISG), has been reported to be involved in innate immune processes and to act as a tumor suppressor in several cancers. However, its immune implication on lung cancer remains unclear. Here, we systemically analyzed the immune association of IFI44L with multiple tumor-infiltrating immune cells (TIICs) and immunomodulators through bioinformatics methods in The Cancer Genome Atlas (TCGA) lung cancer cohorts. Then, the IFI44L-related immunomodulators were selected to construct the prognostic signatures in the lung adenocarcinoma (LUAD) cohort and the lung squamous cell carcinoma (LUSC) cohort, respectively. Concordance index and time-dependent receiver operating characteristics (ROC) curves were applied to evaluate the prognostic signatures. GSE72094 and GSE50081 were used to validate the TCGA-LUAD signature and TCGA-LUSC signature, respectively. A nomogram was established by risk score and clinical features in the LUAD cohort. Finally, the prognostic value and biological function of IFI44L were verified in a real-world cohort and in vitro experiments. The results indicated that IFI44L showed significant correlation with TIICs in LUAD and LUSC samples. Functional enrichment analysis showed that IFI44L may participate in various cancer/immune-related pathways, including JAK/STAT signaling pathway and NF-κB signaling pathway. A total of 44 immunomodulators presented obvious association with IFI44L in the TCGA-LUAD cohort and a robust 10-immunomodulator signature was constructed. Patients in the higher-risk group presented worse prognosis than those in the lower-risk group. Notably, the risk signature was successfully validated in GSE72094. Multivariate Cox regression suggested that the risk signature could act as independent prognostic factors in both TCGA-LUAD and GSE72094 cohorts. Besides, a 17-immunomodulator signature was established in the TCGA-LUSC cohort and similar results were presented through analysis. The nomogram exhibited good accuracy in predicting overall survival (OS) outcome among TCGA-LUAD patients than the risk signature and other clinical features, with the area under curve values being 0.782 at 1 year, 0.825 at 3 years, and 0.792 at 5 years. Finally, tissue microarray analysis indicated that higher expression of IFI44L presented opposite relationship with pathological stage (p = 0.016) and a better outcome among lung cancer patients (p = 0.024). Functional experiments found that IFI44L overexpression significantly inhibited the proliferation, migration, and invasion in LUAD and LUSC cells; RT-qPCR experiments verified the correlation between the expression level of IFI44L with multiple immunomodulators in SPC-A-1 and NCI-H520 cells. In conclusion, our research highlighted that IFI44L is associated with tumor immune infiltration and provided information on IFI44L's immune implication, which indicates that IFI44L has potential clinical immunotherapeutic value and the proposed nomogram is a promising biomarker for non-small cell lung cancer patients.
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The correlation between IFI44L and TIICs and immunomodulators were evaluated by Spearman coefficient.
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sections[18] "Statistical Analysis" paragraph 2
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The correlation between IFI44L and TIICs and immunomodulators were evaluated by Spearman coefficient.
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The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.
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IFI44L is associated with tumor immune infiltration and has potential clinical immunotherapeutic value, while the proposed nomogram is a promising biomarker for non-small cell lung cancer patients.
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In conclusion, our research highlighted that IFI44L is associated with tumor immune infiltration and provided information on IFI44L’s immune implication, which indicates that IFI44L has potential clinical immunotherapeutic value and the proposed nomogram is a promising biomarker for non-small cell lung cancer patients.
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IFI44L is associated with tumor immune infiltration and has potential clinical immunotherapeutic value, while the proposed nomogram is a promising biomarker for non-small cell lung cancer patients.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35047409", "kind": "science-record", "revision": 4, "content_hash": "sha256:801fc0a335ccda31fbe851a73fea78c5b149a677f31f83f1cbf05db2d04ac3de", "created_at": "2026-11-01T17:36:46Z", "updated_at": "2026-11-01T22:05:37Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive Analysis of Immune Implication and Prognostic Value of IFI44L in Non-Small Cell Lung Cancer.", "doi": "10.3389/fonc.2021.798425", "pmid": "35047409", "authors": ["Yong Zeng", "Zhe Zhang", "Hongqiang Chen", "Jun Fan", "Wenbo Yuan", "Jingzhi Li", "Shimeng Zhou", "Wenbin Liu"], "journal": "Frontiers in oncology", "year": 2021, "abstract": "Interferon-induced protein 44-like (IFI44L), a type I interferon-stimulated gene (ISG), has been reported to be involved in innate immune processes and to act as a tumor suppressor in several cancers. However, its immune implication on lung cancer remains unclear. Here, we systemically analyzed the immune association of IFI44L with multiple tumor-infiltrating immune cells (TIICs) and immunomodulators through bioinformatics methods in The Cancer Genome Atlas (TCGA) lung cancer cohorts. Then, the IFI44L-related immunomodulators were selected to construct the prognostic signatures in the lung adenocarcinoma (LUAD) cohort and the lung squamous cell carcinoma (LUSC) cohort, respectively. Concordance index and time-dependent receiver operating characteristics (ROC) curves were applied to evaluate the prognostic signatures. GSE72094 and GSE50081 were used to validate the TCGA-LUAD signature and TCGA-LUSC signature, respectively. A nomogram was established by risk score and clinical features in the LUAD cohort. Finally, the prognostic value and biological function of IFI44L were verified in a real-world cohort and in vitro experiments. The results indicated that IFI44L showed significant correlation with TIICs in LUAD and LUSC samples. Functional enrichment analysis showed that IFI44L may participate in various cancer/immune-related pathways, including JAK/STAT signaling pathway and NF-κB signaling pathway. A total of 44 immunomodulators presented obvious association with IFI44L in the TCGA-LUAD cohort and a robust 10-immunomodulator signature was constructed. Patients in the higher-risk group presented worse prognosis than those in the lower-risk group. Notably, the risk signature was successfully validated in GSE72094. Multivariate Cox regression suggested that the risk signature could act as independent prognostic factors in both TCGA-LUAD and GSE72094 cohorts. Besides, a 17-immunomodulator signature was established in the TCGA-LUSC cohort and similar results were presented through analysis. The nomogram exhibited good accuracy in predicting overall survival (OS) outcome among TCGA-LUAD patients than the risk signature and other clinical features, with the area under curve values being 0.782 at 1 year, 0.825 at 3 years, and 0.792 at 5 years. Finally, tissue microarray analysis indicated that higher expression of IFI44L presented opposite relationship with pathological stage (p = 0.016) and a better outcome among lung cancer patients (p = 0.024). Functional experiments found that IFI44L overexpression significantly inhibited the proliferation, migration, and invasion in LUAD and LUSC cells; RT-qPCR experiments verified the correlation between the expression level of IFI44L with multiple immunomodulators in SPC-A-1 and NCI-H520 cells. In conclusion, our research highlighted that IFI44L is associated with tumor immune infiltration and provided information on IFI44L's immune implication, which indicates that IFI44L has potential clinical immunotherapeutic value and the proposed nomogram is a promising biomarker for non-small cell lung cancer patients.", "claims": [{"id": "claim-method", "statement": "The correlation between IFI44L and TIICs and immunomodulators were evaluated by Spearman coefficient.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35047409", "locator": "sections[18] \"Statistical Analysis\" paragraph 2", "quote": "The correlation between IFI44L and TIICs and immunomodulators were evaluated by Spearman coefficient."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . 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