Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer

Author(s):Show less -

Silva, Virgilio Souza e ^[1] ; Abdallah, Emne Ali ^[2] ; Flores, Bianca de Cassia Troncarelli ^[2] ; Braun, Alexcia Camila ^[2] ; Costa, Daniela de Jesus Ferreira ^[2] ; Ruano, Anna Paula Carreta ^[2] ; Gasparini, Vanessa Alves ^[2] ; Silva, Maria Leticia Gobo ^[3] ; Mendes, Gustavo Gomes ^[4] ; Claro, Laura Carolina Lopez ^[5] ; Calsavara, Vinicius Fernando ^[2] ; Aguiar Junior, Samuel ^[6] ; de Mello, Celso Abdon Lopes ^[1] ; Chinen, Ludmilla Thome Domingos ^{[7, 2]}

Affiliation

^[1] AC Camargo Canc Ctr, Dept Med Oncol, BR-01509900 Sao Paulo - Brazil

^[2] AC Camargo Canc Ctr, Int Res Ctr, BR-01509900 Sao Paulo - Brazil

^[3] AC Camargo Canc Ctr, Dept Radiotherapy, BR-01509900 Sao Paulo - Brazil

^[4] AC Camargo Canc Ctr, Dept Radiol, BR-01509900 Sao Paulo - Brazil

^[5] AC Camargo Canc Ctr, Dept Pathol, BR-01509900 Sao Paulo - Brazil

^[6] AC Camargo Canc Ctr, Dept Pelv Surg, BR-01509900 Sao Paulo - Brazil

^[7] Natl Inst Sci & Technol Oncogen & Therapeut Innov, BR-01509900 Sao Paulo - Brazil

• Document type: Journal article
• Source: CELLS; v. 10, n. 6 JUN 2021.
• Web of Science Citations: 0

Abstract

The heterogeneity of response to neoadjuvant chemoradiotherapy (NCRT) is still a challenge in locally advanced rectal cancer (LARC). The evaluation of thymidylate synthase (TYMS) and RAD23 homolog B (RAD23B) expression in circulating tumor cells (CTCs) provides complementary clinical information. CTCs were prospectively evaluated in 166 blood samples (63 patients) with LARC undergoing NCRT. The primary objective was to verify if the absence of RAD23B/TYMS in CTCs would correlate with pathological complete response (pCR). Secondary objectives were to correlate CTC kinetics before (C1)/after NCRT (C2), in addition to the expression of transforming growth factor-beta receptor I (TGF-beta RI) with survival rates. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). At C1, RAD23B was detected in 54.1% of patients with no pCR and its absence in 91.7% of patients with pCR (p = 0.014); TYMS- was observed in 90% of patients with pCR and TYMS+ in 51.7% without pCR (p = 0.057). Patients with CTC2 > CTC1 had worse disease-free survival (DFS) (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 <= CTC1. TGF-beta RI expression in any time correlated with worse DFS (p = 0.059). To conclude, RAD23B/TYMS and CTC kinetics may facilitate the personalized treatment of LARC. (AU)

• FAPESP's process: 14/50943-1 - INCT 2014: on Oncogenomics and Therapeutic Inovations
• Grantee: Dirce Maria Carraro
• Support Opportunities: Research Projects - Thematic Grants