Abstract 2770: Microbiota, mutational landscape and tumor sidedness of colorrectal cancer

Abstract

Abstract Background: Colorectal cancer (CRC) is one of the most common cancers in the world, and it is one of the leading causes of cancer-related death. New biomarker candidates have emerged as an important prognostic and predictive factor and genetic profile approach has been used in the choice of targeted therapies and in the prediction of drug response. The aim of this study was performed a comprehensive genomic profile and intestinal microbiota characterization in peruvian CRC patients to define biomarkers for decision making. Methods: Patients with CRC diagnosed in 2019 and treated at INEN were included. Tumor samples were collected to assessed the presence of high-risk human papillomavirus (HPV) and Epstein-Bar virus (EBV) by qPCR, microsatellite instability (MSI) by IHC and somatic genomic alterations by next generation sequencing (NGS) using Ampliseq FOCUS panel (Illumina). Fecal samples were self-collected to performed V3-V4 region 16S ribosomal RNA metagenomics sequencing (Illumina). Results: The study included 40 CRC patients with a mean age at diagnosis of 56 (28-90) years, 59.2% were men. Clinical stages were distributed, in I-II (16.5%), III (37.5%), IV (27.5%). The remaining 12.5% had an unknown tumor stage at diagnosis. The 62.5% of patients underwent tumor surgical treatment. Most tumors (85%) were adenocarcinoma NOS and moderately differentiated (65%). Tumor location was rectum (RC; 27.5%), right side colon (RCC; 42.5%) and left side colon (LCC; 30%). Chemotherapy was administered in 30%. The median follow-up period was 11.1 months (2-28). MSI was high (20%), low (10%) and stable (70%). HPV and EBV DNA was detected in 42.5% and 82.5% of CRC patients respectively. The prevalence of genomic alterations was 77.5%. KRAS alterations were found in 47.5% patients. BRAF (5%), NRAS (2.5%), PIK3CA (12.5%), APC (2.5%), and AKT1 (2.5%). All PIK3CA and BRAF variants were found in RCC. No variants were found in the NTRK or HER2 amplifications. Patients with BRAF variant had a median survival rate only 5 months (3-7). MSI-high/low was present only in colon, showing dominance on the RCC (66.7%). Verrucomicrobia, Staphylococcus, Peptostreptococcus and Clostridium were present in both RCC and LCC. Clostridium and Peptostreptococcus were highly enriched in the LCC. Campylobacter and Spirochaeta were found only in the LCC. Surprisingly, Fusobacterium was found in RCC except one patient in LCC. Bifidobacterium and Acinetobacter were present only in LCC and RC. Elusimicrobia, Shigella and WPS-2 were found only in RC. Conclusion: The current pressure to select the best treatment has generated intense interest in the evaluation of CRC molecular alterations characteristic to define prognostic and predictive biomarkers of disease and treatment in our population. This study constitutes the first integrative biomarkers research in peruvian CRC patients showing a diferent molecular signatures between RCC, LCC and RC patients. Citation Format: Bruno A. Muñante Luna, Jhoysi Casas Goñas, Manuel Chumpitaz, Juan Pablo Cerapio, Marcos Santos Chavez, Mariela Huerta-Rosario, Franco Doimi Garcia, Juan F. Olivos Gonzales, Claudia Jiménez Orosco, Daniel Valdivia Leonardo, Luis F. Barreda Bolaños, Silvia Neciosup Delgado, Victor Castro Oliden, Paola Montenegro Beltran, Luis Mas Lopez, Eduardo Payet Meza, Carolina Belmar-López. Microbiota, mutational landscape and tumor sidedness of colorrectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2770.