Downregulated STAT3 and STAT5B are prognostic biomarkers for colorectal cancer and are associated with immune infiltration

Abstract Background Colorectal cancer has high incidence and mortality rates. The signal transducer and activator of transcription (STAT) family plays vital roles in the tumorigenesis and development of colorectal cancer. The expression, prognostic value, and immune function of the STAT family are b...

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Main Authors: Qier Li, Jingzhi Wang, Qingqing Liu, Min Gan, Jianing Yan, Xuan Yu, Yongfu Shao
Format: Article
Language:English
Published: Springer 2025-03-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-02085-2
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author Qier Li
Jingzhi Wang
Qingqing Liu
Min Gan
Jianing Yan
Xuan Yu
Yongfu Shao
author_facet Qier Li
Jingzhi Wang
Qingqing Liu
Min Gan
Jianing Yan
Xuan Yu
Yongfu Shao
author_sort Qier Li
collection DOAJ
description Abstract Background Colorectal cancer has high incidence and mortality rates. The signal transducer and activator of transcription (STAT) family plays vital roles in the tumorigenesis and development of colorectal cancer. The expression, prognostic value, and immune function of the STAT family are becoming much more clearly. Methods Our study collected data from several public data portals such as TCGA (644 samples) and GTEx database (308 samples) and clinical samples (30 samples, China). Then we systematically assessed the expression level and prognostic value of the STAT family in colorectal cancer samples. Moreover, the immune function and immune infiltration levels of prognosis-related STAT members were explored via single cell RNA-seq and spatial transcriptomics technology data. Several useful portals and tools have been utilized such as CancerSEA and TISIDB in single-cell analysis, CBio Cancer Genomics in multidimensional alterations, MethSurv in DNA methylation, and related R packages. Results Our study found that STAT3 and STAT5B were significantly lower in colorectal cancer via multi-omics (P < 0.001). Higher STAT3 and STAT5B level were correlated with better future outcome. Nomograms were developed to predict the distal survival time (C-index = 0.724). The functions of STAT3 and STAT5B are associated with inflammation, the JAK/STAT pathway and the immune response. The major cell types of colorectal cancer were CD4Tconv, CD8T, CD8Tex, Tprolif, Treg and STAT3 and STAT5B widely expressed in these cells. STAT3 and STAT5B both correlated with CD244 and KDR for immune checkpoints. Conclusion STAT3 and STAT5B are downregulated in colorectal cancer and have great potential as prognostic biomarkers and novel immunotherapy targets.
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spelling doaj-art-83f97afd5a244ef895a3033b6cca344b2025-08-20T02:41:32ZengSpringerDiscover Oncology2730-60112025-03-0116111910.1007/s12672-025-02085-2Downregulated STAT3 and STAT5B are prognostic biomarkers for colorectal cancer and are associated with immune infiltrationQier Li0Jingzhi Wang1Qingqing Liu2Min Gan3Jianing Yan4Xuan Yu5Yongfu Shao6Department of Gastroenterology, the First Affiliated Hospital of Ningbo UniversityYancheng First HospitalDepartment of Gastroenterology, the First Affiliated Hospital of Ningbo UniversityDepartment of Gastroenterology, the First Affiliated Hospital of Ningbo UniversityDepartment of Gastroenterology, the First Affiliated Hospital of Ningbo UniversityDepartment of Gastroenterology, the First Affiliated Hospital of Ningbo UniversityDepartment of Gastroenterology, the First Affiliated Hospital of Ningbo UniversityAbstract Background Colorectal cancer has high incidence and mortality rates. The signal transducer and activator of transcription (STAT) family plays vital roles in the tumorigenesis and development of colorectal cancer. The expression, prognostic value, and immune function of the STAT family are becoming much more clearly. Methods Our study collected data from several public data portals such as TCGA (644 samples) and GTEx database (308 samples) and clinical samples (30 samples, China). Then we systematically assessed the expression level and prognostic value of the STAT family in colorectal cancer samples. Moreover, the immune function and immune infiltration levels of prognosis-related STAT members were explored via single cell RNA-seq and spatial transcriptomics technology data. Several useful portals and tools have been utilized such as CancerSEA and TISIDB in single-cell analysis, CBio Cancer Genomics in multidimensional alterations, MethSurv in DNA methylation, and related R packages. Results Our study found that STAT3 and STAT5B were significantly lower in colorectal cancer via multi-omics (P < 0.001). Higher STAT3 and STAT5B level were correlated with better future outcome. Nomograms were developed to predict the distal survival time (C-index = 0.724). The functions of STAT3 and STAT5B are associated with inflammation, the JAK/STAT pathway and the immune response. The major cell types of colorectal cancer were CD4Tconv, CD8T, CD8Tex, Tprolif, Treg and STAT3 and STAT5B widely expressed in these cells. STAT3 and STAT5B both correlated with CD244 and KDR for immune checkpoints. Conclusion STAT3 and STAT5B are downregulated in colorectal cancer and have great potential as prognostic biomarkers and novel immunotherapy targets.https://doi.org/10.1007/s12672-025-02085-2STAT3STAT5BColorectal cancerPrognosisImmune cell infiltration
spellingShingle Qier Li
Jingzhi Wang
Qingqing Liu
Min Gan
Jianing Yan
Xuan Yu
Yongfu Shao
Downregulated STAT3 and STAT5B are prognostic biomarkers for colorectal cancer and are associated with immune infiltration
Discover Oncology
STAT3
STAT5B
Colorectal cancer
Prognosis
Immune cell infiltration
title Downregulated STAT3 and STAT5B are prognostic biomarkers for colorectal cancer and are associated with immune infiltration
title_full Downregulated STAT3 and STAT5B are prognostic biomarkers for colorectal cancer and are associated with immune infiltration
title_fullStr Downregulated STAT3 and STAT5B are prognostic biomarkers for colorectal cancer and are associated with immune infiltration
title_full_unstemmed Downregulated STAT3 and STAT5B are prognostic biomarkers for colorectal cancer and are associated with immune infiltration
title_short Downregulated STAT3 and STAT5B are prognostic biomarkers for colorectal cancer and are associated with immune infiltration
title_sort downregulated stat3 and stat5b are prognostic biomarkers for colorectal cancer and are associated with immune infiltration
topic STAT3
STAT5B
Colorectal cancer
Prognosis
Immune cell infiltration
url https://doi.org/10.1007/s12672-025-02085-2
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