Abstract 4294: An integrative project for tracing the genes involved in depression and cancer (DeCa) in peripheral blood
Authors: Carlos Pedraz, Jillian Wilhelmina Paulina Bracht, Martyna Filipska, Andrés Aguilar, Juan José García, Carlos Cabrera, María González Cao, Santiago Viteri, Imane Chaib, Manuel Fernández-Bruno, Rafael Rosell
Journal: Cancer Research (2020)

Abstract Introduction: Adverse psychological reactions may lead to chronic stress, increasing the risk of depression. Altogether, mood disorders reported prior to diagnosis of cancer negatively influence the prognosis. The first evidence that chronic stress is related to cancer was proven in EGFR mutant non-small-cell lung cancer (NSCLC) patients where the release of norepinephrine activates the β-2 adrenergic receptors in the surface of tumor cells, activating signaling pathways that lead to cancer therapy resistance. Through DeCa we will assess the molecular mechanisms that may be involved in both depression and cancer progression. Blood platelet and extracellular vesicle (EV)-derived biomarkers will be analyzed to explore such correlation and find new therapeutic targets. Methods: Blood from 20 cancer patients was collected at baseline, first evaluation, and upon progression to treatment. Also, patients were asked to fill in the Patient Health Questionnaire 9 to assess depression state at all time points. Blood was processed within 8 hours and centrifuged for 20 minutes at 120xg at room temperature (RT). The platelet rich-plasma was separated and centrifuged for 20 minutes at 360xg at RT. The miRCURY Exosome Serum/Plasma Kit (Qiagen®) was used to isolate EVs from plasma. Treatment with RNAse A (Sigma-Aldrich®) was performed to remove cell-free RNA prior RNA extraction with TRI Reagent (MRC® Inc). Platelets were resuspended in 30 μl RNAlater (Invitrogen®), and RNA was isolated by miRNeasy Serum/plasma kit (Qiagen®). Total RNA was retrotranscribed, and ADRB2, NLRP3, NGF, TRkB, FAK1, and BDNF expression was assessed by qRT-PCR. Results: Preliminary results show an overall consistent expression of FAK1 in both EVs and platelets, when compared with the other biomarkers at all time points. Most biomarkers were found more often expressed in EVs than platelets, with a dominance of FAK1 in platelet samples. Initial EV results show a correlation between BDNF and NGF expression in all time points which seem to be connected with treatment outcome. NLRP3 and ADRB2 also seem to be co-expressed in EV samples. Across all genes analyzed, TrKB was not found expressed in EVs nor in platelets. Moreover, NGF was found expressed only in EVs. Conclusion: DeCa is an ambitious and innovative project that investigates the correlation of two major diseases in order to improve patient outcome and offer a more personalized treatment. In this first phase, we have shown that EVs have different biomarker expression than platelets. Also, results indicate correlation between BDNF-NGF expression in EVs and treatment outcome. Release of these molecules upon stress has been extensively described in literature, so these preliminary results support our hypothesis that molecular changes during acute psychological distress may be implicated in cancer progression. These findings need to be validated in future studies and may pave the way for a dual treatment strategy for both diseases. Citation Format: Carlos Pedraz, Jillian Wilhelmina Paulina Bracht, Martyna Filipska, Andrés Aguilar, Juan José García, Carlos Cabrera, María González Cao, Santiago Viteri, Imane Chaib, Manuel Fernández-Bruno, Rafael Rosell. An integrative project for tracing the genes involved in depression and cancer (DeCa) in peripheral blood [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4294.