title: Gastric adenocarcinoma microRNA profiles in fixed tissue and in plasma reveal cancer-associated and Epstein-Barr virus-related expression patterns.
abstract: MicroRNA expression in formalin-fixed paraffin-embedded tissue (FFPE) or plasma may add value for cancer management. The GastroGenus miR Panel was developed to measure 55 cancer-specific human microRNAs, Epstein-Barr virus (EBV)-encoded microRNAs, and controls. This Q-rtPCR panel was applied to 100 FFPEs enriched for adenocarcinoma or adjacent non-malignant mucosa, and to plasma of 31 patients. In FFPE, microRNAs upregulated in malignant versus adjacent benign gastric mucosa were hsa-miR-21, -155, -196a, -196b, -185, and -let-7i. Hsa-miR-18a, 34a, 187, -200a, -423-3p, -484, and -744 were downregulated. Plasma of cancer versus non-cancer controls had upregulated hsa-miR-23a, -103, and -221 and downregulated hsa-miR-378, -346, -486-5p, -200b, -196a, -141, and -484. EBV-infected versus uninfected cancers expressed multiple EBV-encoded microRNAs, and concomitant dysregulation of four human microRNAs suggests that viral infection may alter cellular biochemical pathways. Human microRNAs were dysregulated between malignant and benign gastric mucosa and between plasma of cancer patients and non-cancer controls. Strong association of EBV microRNA expression with known EBV status underscores the ability of microRNA technology to reflect disease biology. Expression of viral microRNAs in concert with unique human microRNAs provides novel insights into viral oncogenesis and reinforces the potential for microRNA profiles to aid in classifying gastric cancer subtypes. Pilot studies of plasma suggest the potential for a noninvasive addition to cancer diagnostics.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Treece
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Duncan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Weihua
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Elmore
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition; Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Morgan
authors.affiliation: Department of Gastroenterology, Western Regional Hospital, Santa Rosa de Copan, Honduras.
authors.forename: Ricardo L
authors.initials: RL
authors.lastname: Dominguez
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Speck
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Division of Surgical Oncology, Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Meyers
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Gulley
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010865:Pilot Projects; D012334:RNA, Neoplasm / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D012367:RNA, Viral / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology*
chemical_list: D035683:MicroRNAs; D012334:RNA, Neoplasm; D012367:RNA, Viral