The prognostic and predictive values of differential expression of exosomal receptor tyrosine kinases and associated with the PI3K/AKT/mTOR signaling in breast cancer patients undergoing neoadjuvant chemotherapy

Gamze Guney Eskiler; Nur Kazan; Ayten Haciefendi; Asuman Deveci Ozkan; Kayhan Ozdemir; Mirac Ozen; Havva Belma Kocer; Fahri Yilmaz; Suleyman Kaleli; Elvan Sahin; Cemil Bilir

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The prognostic and predictive values of differential expression of exosomal receptor tyrosine kinases and associated with the PI3K/AKT/mTOR signaling in breast cancer patients undergoing neoadjuvant chemotherapy

Gamze Guney Eskiler ^[1] ; Nur Kazan ^[2] ; Ayten Haciefendi ^[2] ; Asuman Deveci Ozkan ^[1] ; Kayhan Ozdemir ^[3] ; Mirac Ozen ^[1] ; Havva Belma Kocer ^[1] ; Fahri Yilmaz ^[1] ; Suleyman Kaleli ^[1] ; Elvan Sahin ^[1] ; Cemil Bilir ^[4]
1. [1] Sakarya University
  
  Sakarya University
  
  Turquía
2. [2] Department of Medical Biology, Institute of Health Sciences, Sakarya University, Sakarya, Turkey
3. [3] Department of General Surgery, Nevsehir Urgup State Hospital, Nevsehir, Turkey
4. [4] Department of Medical Oncology, Faculty of Medicine, Istinye University VM Medical Park Pendik Hospital, Istanbul, Turkey
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Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 25, Nº. 2 (February), 2023, págs. 460-472
Idioma: inglés
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Resumen
- Purpose Cancer cell-derived exosomes are the mediator of the tumor microenvironment and the molecular content of exosomes presents a promising prognostic or predictive marker in tumor progression and the treatment response of cancer patients. The aim of this study was to identify the expression levels of receptor tyrosine kinases (RTKs) and AKT1 and mTOR before and after neoadjuvant chemotherapy (NACT) in the exosomes of BC patients compared with healthy females.
  
  Methods After isolating exosomes in the serum of 25 BC patients and characterization by flow cytometry, the mRNA levels of FGFR2, FGFR3, PDGFRB, AKT1 and mTOR in the exosomes were analyzed by RT-PCR.
  
  Results Our preliminary findings showed that FGFR2, PDGFRB, AKT1 and mTOR levels were significantly upregulated in BC patients before NACT compared with the healthy group (p < 0.05). Furthermore, the mRNA levels PDGFRB and AKT1 were significantly down-regulated after NACT compared with control. PDGFRB expression level could predict pathological non-response and significantly correlated with tumor size after NACT.
  
  Conclusion Therefore, especially FGFR2, PDGFRB and AKT1 could be a therapeutic target as a prognostic marker, whereas PDGFRB may be a promising predictive indicator of therapy response in BC patients. However, the prognostic or predictive role of RTKs and PI3K/AKT/mTOR signaling in the exosomes should be further investigated in a large patient population.