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Plasma Exosome Gene Signature Differentiates Colon Cancer from Healthy Controls.
Vallejos, Paul A; Gonda, Amber; Yu, Jingjing; Sullivan, Brittany G; Ostowari, Arsha; Kwong, Mei Li; Choi, Audrey; Selleck, Matthew J; Kabagwira, Janviere; Fuller, Ryan N; Gironda, Daniel J; Levine, Edward A; Hughes, Christopher C W; Wall, Nathan R; Miller, Lance D; Senthil, Maheswari.
Afiliação
  • Vallejos PA; Department of Basic Science, Division of Biochemistry, Loma Linda University School of Medicine, Loma Linda, CA, USA.
  • Gonda A; Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA.
  • Yu J; Department of Surgery, Division of Surgical Oncology, University of California, Irvine Medical Center, Orange, CA, USA.
  • Sullivan BG; Department of Surgery, Division of Surgical Oncology, University of California, Irvine Medical Center, Orange, CA, USA.
  • Ostowari A; Department of Surgery, Division of Surgical Oncology, University of California, Irvine Medical Center, Orange, CA, USA.
  • Kwong ML; Department of Surgery, Division of Surgical Oncology, University of California, Irvine Medical Center, Orange, CA, USA.
  • Choi A; Division of Surgical Oncology, Loma Linda University Health, Loma Linda, CA, USA.
  • Selleck MJ; Division of Surgical Oncology, Loma Linda University Health, Loma Linda, CA, USA.
  • Kabagwira J; Division of Surgical Oncology, Loma Linda University Health, Loma Linda, CA, USA.
  • Fuller RN; Department of Basic Science, Division of Biochemistry, Loma Linda University School of Medicine, Loma Linda, CA, USA.
  • Gironda DJ; Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA.
  • Levine EA; Department of Basic Science, Division of Biochemistry, Loma Linda University School of Medicine, Loma Linda, CA, USA.
  • Hughes CCW; Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA.
  • Wall NR; Department of Cancer Biology, Wake Forest Health, Winston-Salem, NC, USA.
  • Miller LD; Department of Surgery, Division of Surgical Oncology, Wake Forest Health, Winston-Salem, NC, USA.
  • Senthil M; Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA.
Ann Surg Oncol ; 30(6): 3833-3844, 2023 Jun.
Article em En | MEDLINE | ID: mdl-36864326
ABSTRACT

BACKGROUND:

Liquid biopsies have become an integral part of cancer management as minimally invasive options to detect molecular and genetic changes. However, current options show poor sensitivity in peritoneal carcinomatosis (PC). Novel exosome-based liquid biopsies may provide critical information on these challenging tumors. In this initial feasibility analysis, we identified an exosome gene signature of 445 genes (ExoSig445) from colon cancer patients, including those with PC, that is distinct from healthy controls.

METHODS:

Plasma exosomes from 42 patients with metastatic and non-metastatic colon cancer and 10 healthy controls were isolated and verified. RNAseq analysis of exosomal RNA was performed and differentially expressed genes (DEGs) were identified by the DESeq2 algorithm. The ability of RNA transcripts to discriminate control and cancer cases was assessed by principal component analysis (PCA) and Bayesian compound covariate predictor classification. An exosomal gene signature was compared with tumor expression profiles of The Cancer Genome Atlas.

RESULTS:

Unsupervised PCA using exosomal genes with greatest expression variance showed stark separation between controls and patient samples. Using separate training and test sets, gene classifiers were constructed capable of discriminating control and patient samples with 100% accuracy. Using a stringent statistical threshold, 445 DEGs fully delineated control from cancer samples. Furthermore, 58 of these exosomal DEGs were found to be overexpressed in colon tumors.

CONCLUSIONS:

Plasma exosomal RNAs can robustly discriminate colon cancer patients, including patients with PC, from healthy controls. ExoSig445 can potentially be developed as a highly sensitive liquid biopsy test in colon cancer.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias do Colo / Exossomos Limite: Humans Idioma: En Revista: Ann Surg Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias do Colo / Exossomos Limite: Humans Idioma: En Revista: Ann Surg Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos