Characterization of KRAS Mutational Regression in Oligometastatic Patients

Autor: Alessandro Ottaiano, Roberta Penta de Vera d’Aragona, Anna Maria Trotta, Mariachiara Santorsola, Maria Napolitano, Giosuè Scognamiglio, Fabiana Tatangelo, Paolo Grieco, Silvia Zappavigna, Vincenza Granata, Francesco Perri, Amalia Luce, Giovanni Savarese, Monica Ianniello, Marika Casillo, Nadia Petrillo, Andrea Belli, Francesco Izzo, Guglielmo Nasti, Michele Caraglia, Stefania Scala
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Frontiers in Immunology, Vol 13 (2022)
Druh dokumentu: article
ISSN: 1664-3224
DOI: 10.3389/fimmu.2022.898561
Popis: BackgroundWe previously reported rare regressive genetic trajectories of KRAS pathogenic mutations as a specific hallmark of the genuine oligometastatic status in colorectal cancer (CRC).MethodsSurvival and prognostic impact of disease extent in 140 metastatic CRC patients were evaluated through the Kaplan–Meyer curves and the Log-Rank test. KRAS mutations were assessed through the Illumina NovaSeq 6000 platform and TruSight™ Oncology 500 kit. HLA typing was carried out by PCR with sequence-specific oligonucleotides. Lymphocyte densities in tumors were expressed as cells per square millimeter. NKs isolated and CD8+ from NK-depleted PBMCs were characterized through flow cytometry. CD107a externalization was evaluated as NKs/CD8 cytotoxicity toward human colon cancer cells HT29, SW620, HCT116, and LS174T carrying different KRAS mutations.ResultsThe oligometastatic status was a strong and independent variable for survival (HR: 0.08 vs. polymetastatic disease; 95% CI: 0.02–0.26; p
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