| Title: | Isoform-level transcriptome analysis of peripheral blood mononuclear cells from breast cancer patients identifies a disease-associated RASGEF1A isoform |
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| Authors: | ID Čelešnik, Helena Sabina (Author)
ID Gorenjak, Mario (Author)
ID Krušič, Martina (Author)
ID Crnobrnja, Bojana (Author)
ID Sobočan, Monika (Author)
ID Takač, Iztok (Author)
ID Arko, Darja (Author)
ID Potočnik, Uroš (Author) |
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| Files: |  RAZ_Celesnik_Helena_Sabina_2024.pdf (1,52 MB)
MD5: 1C3BF010E3E1592BEFEE3DDF45BAFE1B
 https://doi.org/10.3390/cancers16183171
https://www.mdpi.com/2072-6694/16/18/3171
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| Language: | English |
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| Work type: | Scientific work |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: | MF - Faculty of Medicine
FKKT - Faculty of Chemistry and Chemical Engineering
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| Abstract: | Breast cancer (BC) comprises multiple subtypes with distinct molecular features, which differ in their interplay with host immunity, prognosis, and treatment. Non-invasive blood analyses can provide valuable insights into systemic immunity during cancer. The aim of this study was to analyze the expression of transcriptional isoforms in peripheral blood mononuclear cells (PBMCs) from BC patients and healthy women to identify potential BC immune biomarkers. Methods: RNA sequencing and isoform-level bioinformatics were performed on PBMCs from 12 triple-negative and 13 luminal A patients. Isoform expression validation by qRT-PCR and clinicopathological correlations were performed in a larger cohort (156 BC patients and 32 healthy women). Results: Transcriptional analyses showed a significant (p < 0.001) decrease in the ENST00000374459 RASGEF1A isoform in PBMCs of BC compared to healthy subjects, indicating disease-related expression changes. The decrease was associated with higher ctDNA and Ki-67 values. Conclusions: The levels of the RASGEF1A transcriptional isoform ENST00000374459 may have the potential to distinguish between BC and healthy subjects. The downregulation of ENST00000374459 in breast cancer is associated with higher proliferation and ctDNA shedding. Specialized bioinformatics analyses such as isoform analyses hold significant promise in the detection of biomarkers, since standard RNA sequencing analyses may overlook specific transcriptional changes that may be disease-associated and biologically important. |
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| Keywords: | breast cancer, peripheral blood, isoform-level RNA-seq, RASGEF1A ENST00000374459, ctDNA, Ki-67 |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Article acceptance date: | 12.09.2024 |
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| Publication date: | 16.09.2024 |
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| Publisher: | MDPI |
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| Year of publishing: | 2024 |
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| Number of pages: | Str. 1-17 |
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| Numbering: | Letn. 16, št. 18, št. članka 3171 |
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| PID: | 20.500.12556/DKUM-91193  |
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| UDC: | 616-006 |
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| ISSN on article: | 2072-6694 |
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| COBISS.SI-ID: | 207753219 |
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| DOI: | 10.3390/cancers16183171 |
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| Publication date in DKUM: | 26.11.2024 |
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| Views: | 221 |
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| Downloads: | 24 |
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| Metadata: |    |
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| Categories: | Misc.
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