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

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

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 Array Express, 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.

HORMONE receptor positive breast cancer; CHEMOKINE receptors; ALTERNATIVE RNA splicing; ESTROGEN receptors; CANCER genes

Frontiers in Genetics, 2023, p1

1664-8021

Academic Journal

10.3389/fgene.2023.1230998