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Article

The Importance of Sex in the Discovery of Colorectal Cancer Prognostic Biomarkers

1
Science for Life Laboratory, Department of Protein Science, KTH Royal Institute of Technology, 171 21 Solna, Sweden
2
Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Huddinge, Sweden
3
Department of Oncology and Pathology, Karolinska Institutet, 171 76 Stockholm, Sweden
4
Department of Clinical Pathology and Cytology, Karolinska University Laboratory, Södersjukhuset, 118 83 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
Academic Editor: Luca Agnelli
Int. J. Mol. Sci. 2021, 22(3), 1354; https://doi.org/10.3390/ijms22031354
Received: 29 December 2020 / Revised: 25 January 2021 / Accepted: 27 January 2021 / Published: 29 January 2021
(This article belongs to the Section Molecular Genetics and Genomics)
Colorectal cancer (CRC) is the third leading cause of cancer deaths. Advances within bioinformatics, such as machine learning, can improve biomarker discovery and ultimately improve CRC survival rates. There are clear sex differences in CRC characteristics, but the impact of sex has not been considered with regards to CRC biomarkers. Our aim here was to investigate sex differences in the transcriptome of a normal colon and CRC, and between paired normal and tumor tissue. Next, we attempted to identify CRC diagnostic and prognostic biomarkers and investigate if they are sex-specific. We collected paired normal and tumor tissue, performed RNA-seq, and applied feature selection in combination with machine learning to identify the top CRC diagnostic biomarkers. We used The Cancer Genome Atlas (TCGA) data to identify sex-specific CRC diagnostic biomarkers and performed an overall survival analysis to identify sex-specific prognostic biomarkers. We found transcriptomic sex differences in both the normal colon tissue and in CRC. Forty-four of the top-ranked biomarkers were sex-specific and 20 biomarkers showed a sex-specific prognostic value. Our data show the importance of sex in the discovery of CRC biomarkers. We propose 20 sex-specific CRC prognostic biomarkers, including ESM1, GUCA2A, and VWA2 for males and CLDN1 and FUT1 for females. View Full-Text
Keywords: biomarkers; colorectal cancer; feature selection; machine learning; sex differences biomarkers; colorectal cancer; feature selection; machine learning; sex differences
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MDPI and ACS Style

Hases, L.; Ibrahim, A.; Chen, X.; Liu, Y.; Hartman, J.; Williams, C. The Importance of Sex in the Discovery of Colorectal Cancer Prognostic Biomarkers. Int. J. Mol. Sci. 2021, 22, 1354. https://doi.org/10.3390/ijms22031354

AMA Style

Hases L, Ibrahim A, Chen X, Liu Y, Hartman J, Williams C. The Importance of Sex in the Discovery of Colorectal Cancer Prognostic Biomarkers. International Journal of Molecular Sciences. 2021; 22(3):1354. https://doi.org/10.3390/ijms22031354

Chicago/Turabian Style

Hases, Linnea, Ahmed Ibrahim, Xinsong Chen, Yanghong Liu, Johan Hartman, and Cecilia Williams. 2021. "The Importance of Sex in the Discovery of Colorectal Cancer Prognostic Biomarkers" International Journal of Molecular Sciences 22, no. 3: 1354. https://doi.org/10.3390/ijms22031354

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