Isoform switching leads to downregulation of cytokine producing genes in estrogen receptor positive breast cancer

Mohammad Shahbaz Khan; Waqar Hanif; Nada Alsakhen; Basit Jabbar; Israa M Shamkh; Ahad Amer Alsaiari; Mazen Almehmadi; Saad Alghamdi; Afnan Shakoori; Dunia A Al Farraj; Saeedah Musaed Almutairi; Yasser Hussein Issa Mohammed; Amr S Abouzied; Aziz-Ur Rehman; Bader Huwaimel

doi:10.3389/fgene.2023.1230998

Isoform switching leads to downregulation of cytokine producing genes in estrogen receptor positive breast cancer

Front Genet. 2023 Oct 13:14:1230998. doi: 10.3389/fgene.2023.1230998. eCollection 2023.

Authors

Mohammad Shahbaz Khan¹, Waqar Hanif², Nada Alsakhen³, Basit Jabbar⁴, Israa M Shamkh⁵, Ahad Amer Alsaiari⁶, Mazen Almehmadi⁶, Saad Alghamdi⁷, Afnan Shakoori⁷, Dunia A Al Farraj⁸, Saeedah Musaed Almutairi⁸, Yasser Hussein Issa Mohammed⁹, Amr S Abouzied^{10

11}, Aziz-Ur Rehman¹², Bader Huwaimel^{10

13}

Affiliations

¹ Children's National Hospital, Washington, DC, United States.
² Department of Bioinformatics, Department of Sciences, School of Interdisciplinary Engineering & Science (SINES), National University of Sciences and Technology (NUST), Islamabad, Pakistan.
³ Department of Chemistry, Faculty of Science, The Hashemite University, Zarqa, Jordan.
⁴ Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.
⁵ Chemo and Bioinformatics Lab, Bio Search Research Institution, Giza, Egypt.
⁶ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia.
⁷ Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia.
⁸ Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia.
⁹ Department of Biochemistry, Faculty of Applied Science, University of Hajjah, Hajjah, Yemen.
¹⁰ Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail, Saudi Arabia.
¹¹ Department of Pharmaceutical Chemistry, National Organization for Drug Control and Research (NOD CAR), Giza, Egypt.
¹² Keystone Pharmacogenomics LLC, Bensalem, PA, United States.
¹³ Medical and Diagnostic Research Center, University of Hail, Hail, Saudi Arabia.

Abstract

Objective: Estrogen receptor breast cancer (BC) is characterized by the expression of estrogen receptors. It is the most common cancer among women, with an incidence rate of 2.26 million cases worldwide. The aim of this study was to identify differentially expressed genes and isoform switching between estrogen receptor positive and triple negative BC samples. Methods: The data were collected from ArrayExpress, followed by preprocessing and subsequent mapping from HISAT2. Read quantification was performed by StringTie, and then R package ballgown was used to perform differential expression analysis. Functional enrichment analysis was conducted using Enrichr, and then immune genes were shortlisted based on the ScType marker database. Isoform switch analysis was also performed using the IsoformSwitchAnalyzeR package. Results: A total of 9,771 differentially expressed genes were identified, of which 86 were upregulated and 117 were downregulated. Six genes were identified as mainly associated with estrogen receptor positive BC, while a novel set of ten genes were found which have not previously been reported in estrogen receptor positive BC. Furthermore, alternative splicing and subsequent isoform usage in the immune system related genes were determined. Conclusion: This study identified the differential usage of isoforms in the immune system related genes in cancer cells that suggest immunosuppression due to the dysregulation of CXCR chemokine receptor binding, iron ion binding, and cytokine activity.

Keywords: CXCR chemokine receptor; breast cancer; cytokine; differential expression; estrogen receptor; functional enrichment; immunosuppression; isoform switching.