ESTRO 2022 - Abstract Book

S437

Abstract book

ESTRO 2022

PD-0487 Radiotherapy-induced gene expression changes in breast cancer cell lines

C. Gomà 1,2 , F. Brasó-Maristany 2 , N. Lorman-Carbó 2 , A. Prat 2,3 , M. Mollà 1,2

1 Hospital Clínic de Barcelona, Department of Radiation Oncology, Barcelona, Spain; 2 IDIBAPS, Translational Genomics and Targeted Therapies in Solid Tumors, Barcelona, Spain; 3 Hospital Clínic de Barcelona, Department of Medical Oncology, Barcelona, Spain Purpose or Objective A potential synergistic effect between pre-operative radiotherapy and systemic therapies for high-risk breast cancer (BC) is currently being investigated in a handful of ongoing clinical trials. However, the scarce in vivo data on gene expression changes induced by radiotherapy come from low-risk (i.e. Luminal A) breast cancer. The purpose of this work is to investigate radiotherapy-induced gene expression changes in high-risk (Luminal B, HER2-enriched and Basal-like) breast cancer cell lines. Materials and Methods Six different human breast cancer cell lines (BT474, MCF7, MDA-MB-468, MD-MA-453, T47D and ZR751) were investigated (see Table 1). They were irradiated with a single fraction of 6, 8 and 10 Gy using a clinical 6 MV photon beam. RNA was extracted before and 72 hours after irradiation. For the 6 Gy irradiation, RNA was also extracted 6 and 21 days after irradiation. The RNA was profiled using the NanoString nCounter Elements XT panel, which includes the 50 genes within the PAM50 signature. PAM50 intrinsic subtypes and other signatures (e.g. Proliferation score) were computed using R. All experiments were repeated at least 3 times. Table 1: Description of the 6 human breast cancer cell lines investigated in this work, in terms of intrinsic molecular subtype, hormone receptors status and HER2 status. Cell line Intrinsic subtype HR HER2 BT474 HER2-enriched + + MCF7 Luminal B + - MDA-MB-468 Basal-like - - MDA-MD-473 HER2-enriched - - T47D Luminal B + - ZR751 HER2-enriched + - Results We found that radiotherapy induces significant gene expression changes in HR+/HER2-negative cell lines, while HER2+ and triple-negative cell lines did not seem to be affected by the radiation doses investigated in this work. For HR+/HER2- negative cell lines, we identified a strong RT-induced downregulation of proliferative genes, together with a notable upregulation of genes related to the HER2-enriched (HER2-E) subtype, such as ERBB2 , GRB7 or TMEM45B (see figure 1), 72 hours after irradiation. Three weeks after irradiation, the upregulation of HER2-E-related genes persisted, while the expression of proliferative genes returned to the baseline level. Figure 1: Luminal B, HER2-enriched and proliferation signatures, as well as ERBB2 , GRB7 and TMEM45 gene expression, as a function of radiation dose, for MCF7 (top) and T47D (bottom) cell lines.