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Cell Biosci. 2014 Jul 9;4:35. doi: 10.1186/2045-3701-4-35. eCollection 2014.

Clinical biomarkers of pulmonary carcinoid tumors in never smokers via profiling miRNA and target mRNA.

Author information

  • 1Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA ; Thoracic Surgery Department, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
  • 2Department of Oncology, Division of Medical Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
  • 3Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
  • 4Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
  • 5Department of Pathology, Medical College of Wisconsin Cancer Center, Milwaukee, Wisconsin, USA.
  • 6Medical Genome Facility, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
  • 7Department of Molecular Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
  • 8Department of Cancer Center and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
  • 9Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
  • 10Department of Surgery, Division of General Thoracic Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.

Abstract

BACKGROUND:

miRNAs play key regulatory roles in cellular pathological processes. We aimed to identify clinically meaningful biomarkers in pulmonary carcinoid tumors (PCTs), a member of neuroendocrine neoplasms, via profiling miRNAs and mRNAs.

RESULTS:

From the total of 1145 miRNAs, we obtained 16 and 17 miRNAs that showed positive and negative fold changes (FCs, tumors vs. normal tissues) in the top 1% differentially expressed miRNAs, respectively. We uncovered the target genes that were predicted by at least two prediction tools and overlapped by at least one-half of the top miRNAs, which yielded 44 genes (FC<-2) and 56 genes (FC>2), respectively. Higher expressions of CREB5, PTPRB and COL4A3 predicted favorable disease free survival (Hazard ratio: 0.03, 0.19 and 0.36; P value: 0.03, 0.03 and 0.08). Additionally, 79 mutated genes have been found in nine PCTs where TP53 was the only repeated mutation.

CONCLUSION:

We identified that the expressions of three genes have clinical implications in PCTs. The biological functions of these biomarkers warrant further studies.

KEYWORDS:

Carcinoid; Survival; mRNA; miRNA

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