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KRAS expression is a prognostic indicator and associated with immune infiltration in breast cancer

Breast Cancer volume 28, pages 379–386 (2021)Cite this article

Abstract

Background

Breast cancer is the most common cancer and the leading cause of death among women. KRAS is known as an oncogene, its expression also associates with cancer prognosis. The purpose of this study was to investigate the prognostic value of KRAS expression in breast cancer and its relationship with immune infiltration.

Methods

Firstly, the expression level and methylation of KRAS were analyzed. Then survival analysis was used to verify the prognostic capability of KRAS expression. After that, gene functional enrichment analysis was performed. The relationship between KRAS gene expression and immune infiltration was researched later.

Results

The expression level of KRAS in breast cancer was increased (P = 2.2e−16). Tumor KRAS expression in the subtypes of basal-like, HER2-enriched, Luminal A and Luminal B were 1.64, 1.67, 1.51 and 1.42 times of normal, respectively. 13 methylation sites were different between tumor and normal tissues and associated with KRAS expression. Subsequently, Kaplan–Meier analysis suggested that the high KRAS expression group had a poor prognosis (P = 0.0028). In multivariate Cox regression analysis, KRAS expression was an independent prognostic indicator (HR = 1.353, 95% CI 1.009–1.814, P = 0.044). Gene Ontology (GO) analysis showed enrichment of epidermal growth associated pathways. Additionally, different KRAS expression levels represented different tumor immune infiltration status, which may be caused by the influence of the RAS/MAPK and RAS/PI3K pathways on the level of PD-L1.

Conclusion

This study suggests that KRAS expression can be used as a prognostic indicator of breast cancer, and it is closely related to tumor immune infiltration.

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Data availability

The gene expression data is available in UCSC Xena (https://xenabrowser.net) and the methylation data can download from MEXPRESS database (https://mexpress.be/index.html). The validation Kaplan–Meier diagram was drawn on Kaplan–Meier Plotter (https://kmplot.com/analysis/). The molecular correlation data is available in TIMER database (https://cistrome.shinyapps.io/timer/). The statistical analysis used an open source software R 3.6.1 (https://www.r-project.org/).

Abbreviations

GO:

Gene Ontology

TNBC:

Triple-negative breast cancer

OS:

Overall survival

ssGSEA:

Single-sample gene set enrichment analysis

HR:

Hazard ratio

CI:

Confidence interval

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Acknowledgements

We thank Tianyi Zhou for the Internet technical assistance and the work by Yixin Wang and his (her) colleagues.

Funding

This study was supported in part by Guangxi Medical University Innovation and Entrepreneurship Training Program (Grant no. 201910598261).

Author information

Author notes

  1. Haiqi Liang and Guiyou Zhou contributed equally to this work.

Affiliations

  1. Guangxi Medical University, 22 Shuang-Yong Road, Nanning, 560021, Guangxi, China

    Haiqi Liang, Guiyou Zhou, Lianhua Lv, Jiarong Lu & Jiashun Peng

Authors
  1. Haiqi Liang
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  2. Guiyou Zhou
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  3. Lianhua Lv
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Contributions

HL, JL, and GZ designed and conceived the study. JP downloaded the data from online databases. HL and JL analyzed the data. GZ and LL wrote the manuscript.

Corresponding author

Correspondence to Haiqi Liang.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Supplementary file1 Supplementary Fig. 1 The Kaplan–Meier diagram of OS in validation cohort (GSE2034) (JPG 118 kb)

12282_2020_1170_MOESM2_ESM.jpg

Supplementary file2 Supplementary Fig. 2 The Kaplan–Meier diagram of OS for breast cancer molecular subtypes (high KRAS expression group vs low KRAS expression group). a Luminal A (133 vs 154); b Luminal B (48 vs 26); c HER2-enriched (17 vs 15); d basal-like (48 vs 38) (JPG 294 kb)

12282_2020_1170_MOESM3_ESM.jpg

Supplementary file3 Supplementary Fig. 3 Comparison of immune infiltration in breast cancer molecular subtypes with high- and low-KRAS expression level. a Luminal A; b Luminal B; c HER2-enriched; d basal-like. “*” represents P < 0.05, “**” represents P < 0.01, “***” represents P < 0.001 (JPG 500 kb)

12282_2020_1170_MOESM4_ESM.doc

Supplementary file4 Supplement Table 1 Clinical and pathological characteristics of patients and their tumors in cohort GSE2034 (include training set and validation set) (DOC 50 kb)

12282_2020_1170_MOESM5_ESM.doc

Supplementary file5 Supplementary Table 2 Correlation analysis between KRAS and gene markers of tumor immune infiltrate cells (DOC 70 kb)

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Liang, H., Zhou, G., Lv, L. et al. KRAS expression is a prognostic indicator and associated with immune infiltration in breast cancer. Breast Cancer 28, 379–386 (2021). https://doi.org/10.1007/s12282-020-01170-4

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  • DOI: https://doi.org/10.1007/s12282-020-01170-4

Keywords

  • Biomarker
  • Breast cancer
  • Immune infiltration
  • KRAS expression
  • Prognosis