2026-04-13T02:21:04Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/63782026-04-02T07:33:12Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Hernando Cubero, Jorge author Fasani, Roberta author Jiménez Flores, José Antonio author Elez Fernandez, Mª Elena author Tabernero, Josep author Nuciforo, Paolo Giovanni author Capdevila Castillon, Jaume author Landolfi, Stefania author Comas Navarro, Raquel author Ruiz Pace, Fiorella author Serna, Garazi author Dienstmann, Rodrigo author Alonso, Lola author 2021-10-04T12:58:49Z 2021-10-04T12:58:49Z 2020-10 Fusobacterium nucleatum; Càncer de recte avançat local; Quimioteràpia preoperatòria Fusobacterium nucleatum; Cáncer de recto avanzado local; Quimiorradioterapia preoperatoria Fusobacterium nucleatum; Locally advanced rectal cancer; Preoperative chemoradiotherapy Background Accumulating evidence has identified Fusobacterium as an important pathogenic gut bacterium associated with colorectal cancer. Nevertheless, only limited data exist about the role of this bacterium in locally advanced rectal cancer (LARC). In this study, we quantified Fusobacterium nucleatum in untreated and post-neoadjuvant chemoradiotherapy (nCRT) samples from LARC patients and investigated its association with therapy response and survival. Patients and methods A total of 254 samples from 143 patients with rectal adenocarcinomas were analyzed for the presence and abundance of F. nucleatum using RNA in situ hybridization and digital image analysis. Assay accuracy was determined using infected cell lines and tumor samples with available quantitative PCR data. We studied the impact of F. nucleatum load on pathologic complete response and relapse-free survival. Treatment-induced changes were evaluated in paired pre- and post-nCRT samples (n = 71). Finally, tumor microenvironment changes during nCRT were assessed in paired samples (n = 45) by immune contexture analysis. Results F. nucleatum tissue levels by RNA in situ hybridization strongly correlated with quantitative PCR (r = 0.804, P < 0.001). F. nucleatum abundance was higher in untreated [median, 7.4; 95% confidence interval (3.7–16.2)] compared with treated [median, 1.6; 95% confidence interval (1.3–2.4)] tumors (P <0.001) with 58% (73/126) and 26% (22/85) positive tumors, respectively (P < 0.001). Baseline F. nucleatum levels were not associated with pathologic complete response. F. nucleatum positivity after nCRT, but not baseline status, significantly increased risk of relapse [hazard ratio = 7.5, 95% confidence interval (3.0–19.0); P < 0.001]. Tumors that turned F. nucleatum-negative after nCRT had a strong increase in CD8+ T cells post-nCRT (P < 0.001), while those that persisted F. nucleatum-positive after nCRT lacked CD8+ T cells induction in post-nCRT samples compared with baseline (P = 0.69). Conclusion F. nucleatum persistence post-nCRT is associated with high relapse rates in LARC, potentially linked to suppression of immune cytotoxicity. Bacteris gramnegatius Recte - Càncer - Quimioteràpia Recte - Càncer - Radioteràpia DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Rectal Neoplasms ORGANISMS::Bacteria::Bacteria::Gram-Negative Bacteria::Gram-Negative Anaerobic Bacteria::Gram-Negative Anaerobic Straight, Curved, and Helical Rods::Fusobacterium::Fusobacterium nucleatum ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::Chemoradiotherapy ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales::neoplasias del recto ORGANISMOS::Bacteria::Bacteria::bacterias gramnegativas::bacterias anaerobias gramnegativas::bacilos anaerobios gramnegativos, rectos, curvos y espirales::Fusobacterium::Fusobacterium nucleatum TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::quimiorradioterapia Fusobacterium nucleatum persistence and risk of recurrence after preoperative treatment in locally advanced rectal cancer