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Research Article
Prognostic Biomarker MUC4 Mutations in Colon Adenocarcinoma Correlating with Tumor Microenvironment
Feng Gao
Xinjiang Medical University
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Immunotherapy is a new strategy for Colorectal cancer (CRC) treatment. Tumor mutation burden (TMB) may act as an emerging biomarker for predicting responses to immunotherapy. Nevertheless, no studies investigate if these gene mutations correlate to TMB and tumor-infiltrating immune cells.
Methods: Somatic mutation data for CRC samples were obtained from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) datasets. Then, we investigated the relationship between these mutant genes, TMB and overall survival outcomes. GSEA analysis was performed to explore the underlying mechanism of mutant gene. Finally, we further verified the connection between gene mutations and immune response.
Results: We identified 17 common mutant genes shared by both two cohorts. Further analysis found that MUC4 mutation was strongly related to higher TMB and predicted a poorer prognosis. Moreover, functional enrichment analysis of samples with MUC4 mutation revealed that they were involved in regulating the natural killer cell mediated cytotoxicity signaling pathway. Significant changes in the proportion of the immune cells of CD8+ T cells, activated NK cells, M1 macrophages and resting memory CD4+ T cells were observed using the CIBERSORT algorithm.
Conclusions: Our research revealed that MUC4 mutation significantly correlated with increased TMB, a worse prognosis and modulating the immune microenvironment, which may be considered a biomarker to predict the outcome of the immune response in colorectal cancer.
Keywords
colon adenocarcinoma， MUC4，tumor mutation burden, tumor microenvironment, prognosis
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CURRENT STATUS: Under Review
Version 1
Posted 07 Jan, 2021
No community comments so far
Review #1 received
Received 20 Jan, 2021
Reviewer #2 agreed
On 15 Jan, 2021
Reviewer #4 agreed
On 15 Jan, 2021
Reviewer #1 agreed
On 15 Jan, 2021
Reviewer #3 agreed
On 15 Jan, 2021
Reviewers invited
Invitations sent on 14 Jan, 2021
Editor assigned
On 11 Jan, 2021
Editor invited
On 04 Jan, 2021
Submission checks complete
On 04 Jan, 2021
First submitted
On 29 Dec, 2020
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Subject Areas
Bioinformatics
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This preprint is under consideration at BMC Bioinformatics. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Prognostic Biomarker MUC4 Mutations in Colon Adenocarcinoma Correlating with Tumor Microenvironment
Feng Gao
Xinjiang Medical University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 1
Posted 07 Jan, 2021
No community comments so far
Review #1 received
Received 20 Jan, 2021
Reviewer #2 agreed
On 15 Jan, 2021
Reviewer #4 agreed
On 15 Jan, 2021
Reviewer #1 agreed
On 15 Jan, 2021
Reviewer #3 agreed
On 15 Jan, 2021
Reviewers invited
Invitations sent on 14 Jan, 2021
Editor assigned
On 11 Jan, 2021
Editor invited
On 04 Jan, 2021
Submission checks complete
On 04 Jan, 2021
First submitted
On 29 Dec, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Bioinformatics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Immunotherapy is a new strategy for Colorectal cancer (CRC) treatment. Tumor mutation burden (TMB) may act as an emerging biomarker for predicting responses to immunotherapy. Nevertheless, no studies investigate if these gene mutations correlate to TMB and tumor-infiltrating immune cells.
Methods: Somatic mutation data for CRC samples were obtained from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) datasets. Then, we investigated the relationship between these mutant genes, TMB and overall survival outcomes. GSEA analysis was performed to explore the underlying mechanism of mutant gene. Finally, we further verified the connection between gene mutations and immune response.
Results: We identified 17 common mutant genes shared by both two cohorts. Further analysis found that MUC4 mutation was strongly related to higher TMB and predicted a poorer prognosis. Moreover, functional enrichment analysis of samples with MUC4 mutation revealed that they were involved in regulating the natural killer cell mediated cytotoxicity signaling pathway. Significant changes in the proportion of the immune cells of CD8+ T cells, activated NK cells, M1 macrophages and resting memory CD4+ T cells were observed using the CIBERSORT algorithm.
Conclusions: Our research revealed that MUC4 mutation significantly correlated with increased TMB, a worse prognosis and modulating the immune microenvironment, which may be considered a biomarker to predict the outcome of the immune response in colorectal cancer.
Figure 1
Figure 2
Figure 3
Figure 4