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Research article
Nan Liu
Beijing Anzhen Hospital, Capital Medical University
Corresponding Author
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Background: Breast cancer is one of the most frequently diagnosed cancers among women worldwide. Alterations in the tumor microenvironment (TME) have been increasingly recognized as key in the development and progression of breast cancer in recent years. To deeply comprehend the gene expression profiling of the TME and identify immunological targets, as well as determine the relationship between gene expression and different prognoses is highly critical.
Results: The stromal/immune scores of breast cancer patients from The Cancer Genome Atlas were employed to comprehensively evaluate the TME. Although the TME did not correlate with the stages of breast cancer, it was closely associated with the subtypes of breast cancer and gene mutations (CDH1, TP53 and PTEN), and had immunological characteristics. Based on Gene Ontology (GO) functional enrichment analysis, the upregulated genes from the high vs low immune score groups were mainly involved in T cell activation, the external side of the plasma membrane, and receptor ligand activity. We further analyzed and screened the overlapping genes of the top 3 GO terms and upregulated differentially expressed genes (DEGs). Overall survival, time-dependent receiver operating characteristic (ROC), and protein-protein interaction (PPI) network analyses revealed that the genes of the top GO terms of the upregulated DEGs from the high vs low immune score groups exhibited better prognosis in breast cancer; 15 of them were related to good prognosis in breast cancer, especially CD226 and KLRC4-KLRK1.
Conclusions: High CD226 and KLRC4-KLRK1 expression levels were identified and validated to correlate with better overall survival in specific stages or subtypes of breast cancer. CD226, KLRC4-KLRK1 and other new targets seem to be promising avenues for promoting antitumor targeted immunotherapy in breast cancer.
Keywords
breast cancer, tumor microenvironment, immune-related gene, prognostic signature, immunotherapy
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This is a list of supplementary files associated with this preprint. Click to download.
- FigureS1.pdf
Figure S1. The high and low stromal/immune score groups did not show any survival differences in the four breast cancer subtypes. The high and low stromal score groups’ survival probability differences in the (A) luminal A, (B) luminal B, (C) HER2-enriched, (D) basal-like subtypes. The high and low immune score groups’ survival probability differences in the (E) luminal A, (F) luminal B, (G) HER2-enriched, and (H) basal-like subtypes. P <0.05 in the log-rank test.
- FigureS2.pdf
Figure S2. The high and low expression of CD226 and KLRC4-KLRK1 did not show any survival differences in stage I, the luminal A subtype, the HER2-enriched subtype or the basal-like subtype of breast cancer. The survival probability differences of high and low (A) CD226 and (B) KLRC4-KLRK1 expression in stage I breast cancer; the survival probability differences of high and low CD226 expression in the (C) luminal A, (D) luminal B, and (E) HER2-enriched subtypes of breast cancer; the survival probability differences of high and low KLRC4-KLRK1 expression in the (F) luminal A, (G) luminal B, and (H) HER2-enriched subtypes of breast cancer. P <0.05 in the log-rank test.
- TableS1.docx
Table S1. The overlapping genes between the upregulated DEGs from the high vs low immune score groups and the gene datasets
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View the published article at BMC Cancer.
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Reviewer #2 agreed
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Editorial decision: Major revision
On 20 Jul, 2020
Review #2 received
Received 18 Jul, 2020
Review #1 received
Received 07 Jul, 2020
Reviewer #2 agreed
On 23 Jun, 2020
Reviewer #1 agreed
On 17 Jun, 2020
Editor assigned
On 16 Jun, 2020
Reviewers invited
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
See the published version of this preprint at BMC Cancer.
This is a preprint, 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
Nan Liu
Beijing Anzhen Hospital, Capital 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: Published
View the published article at BMC Cancer.
Version 3
Posted 20 Oct, 2020
No community comments so far
Reviewer #2 agreed
On 17 Dec, 2020
Review #1 received
Received 28 Nov, 2020
Reviewer #1 agreed
On 11 Nov, 2020
Reviewers invited
Invitations sent on 10 Nov, 2020
Editor assigned
On 12 Oct, 2020
Submission checks complete
On 11 Oct, 2020
Editor invited
On 11 Oct, 2020
No comments provided
Editorial decision: Minor revision
On 07 Oct, 2020
Review #2 received
Received 30 Sep, 2020
Reviewer #3 agreed
On 21 Sep, 2020
Review #1 received
Received 19 Sep, 2020
Reviewer #2 agreed
On 10 Sep, 2020
Reviewer #1 agreed
On 07 Sep, 2020
Reviewers invited
Invitations sent on 24 Aug, 2020
Editor assigned
On 12 Aug, 2020
Submission checks complete
On 11 Aug, 2020
Editor invited
On 11 Aug, 2020
No comments provided
Editorial decision: Major revision
On 20 Jul, 2020
Review #2 received
Received 18 Jul, 2020
Review #1 received
Received 07 Jul, 2020
Reviewer #2 agreed
On 23 Jun, 2020
Reviewer #1 agreed
On 17 Jun, 2020
Editor assigned
On 16 Jun, 2020
Reviewers invited
Invitations sent on 16 Jun, 2020
Submission checks complete
On 15 Jun, 2020
Editor invited
On 15 Jun, 2020
First submitted
On 14 Jun, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Cancer.
Background: Breast cancer is one of the most frequently diagnosed cancers among women worldwide. Alterations in the tumor microenvironment (TME) have been increasingly recognized as key in the development and progression of breast cancer in recent years. To deeply comprehend the gene expression profiling of the TME and identify immunological targets, as well as determine the relationship between gene expression and different prognoses is highly critical.
Results: The stromal/immune scores of breast cancer patients from The Cancer Genome Atlas were employed to comprehensively evaluate the TME. Although the TME did not correlate with the stages of breast cancer, it was closely associated with the subtypes of breast cancer and gene mutations (CDH1, TP53 and PTEN), and had immunological characteristics. Based on Gene Ontology (GO) functional enrichment analysis, the upregulated genes from the high vs low immune score groups were mainly involved in T cell activation, the external side of the plasma membrane, and receptor ligand activity. We further analyzed and screened the overlapping genes of the top 3 GO terms and upregulated differentially expressed genes (DEGs). Overall survival, time-dependent receiver operating characteristic (ROC), and protein-protein interaction (PPI) network analyses revealed that the genes of the top GO terms of the upregulated DEGs from the high vs low immune score groups exhibited better prognosis in breast cancer; 15 of them were related to good prognosis in breast cancer, especially CD226 and KLRC4-KLRK1.
Conclusions: High CD226 and KLRC4-KLRK1 expression levels were identified and validated to correlate with better overall survival in specific stages or subtypes of breast cancer. CD226, KLRC4-KLRK1 and other new targets seem to be promising avenues for promoting antitumor targeted immunotherapy in breast cancer.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
This is a list of supplementary files associated with this preprint. Click to download.
- FigureS1.pdf
Figure S1. The high and low stromal/immune score groups did not show any survival differences in the four breast cancer subtypes. The high and low stromal score groups’ survival probability differences in the (A) luminal A, (B) luminal B, (C) HER2-enriched, (D) basal-like subtypes. The high and low immune score groups’ survival probability differences in the (E) luminal A, (F) luminal B, (G) HER2-enriched, and (H) basal-like subtypes. P <0.05 in the log-rank test.
- FigureS2.pdf
Figure S2. The high and low expression of CD226 and KLRC4-KLRK1 did not show any survival differences in stage I, the luminal A subtype, the HER2-enriched subtype or the basal-like subtype of breast cancer. The survival probability differences of high and low (A) CD226 and (B) KLRC4-KLRK1 expression in stage I breast cancer; the survival probability differences of high and low CD226 expression in the (C) luminal A, (D) luminal B, and (E) HER2-enriched subtypes of breast cancer; the survival probability differences of high and low KLRC4-KLRK1 expression in the (F) luminal A, (G) luminal B, and (H) HER2-enriched subtypes of breast cancer. P <0.05 in the log-rank test.
- TableS1.docx
Table S1. The overlapping genes between the upregulated DEGs from the high vs low immune score groups and the gene datasets
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