Abstract

BackgroundLung cancer is a major cause of cancer-related mortality worldwide, and around two-thirds of patients have metastasis at diagnosis. Thus, detecting lung cancer at an early stage could reduce mortality. Aberrant levels of circulating small non-coding RNAs (small ncRNAs) are potential diagnostic or prognostic markers for lung cancer. We aimed to identify plasma small ncRNA pairs that could be used for early screening and detection of lung adenocarcinoma (LAC).ResultsA panel of seven small ncRNA pair ratios could differentiate patients with LAC or benign lung disease from high-risk controls with an area under the curve (AUC) of 100.0%, a sensitivity of 100.0% and a specificity of 100.0% at the training stage (which included 50 patients with early-stage LAC, 35 patients with benign diseases and 29 high-risk controls) and an AUC of 90.2%, a sensitivity of 91.5% and a specificity of 80.4% at the validation stage (which included 44 patients with early-stage LAC, 32 patients with benign diseases and 51 high-risk controls). The same panel could distinguish LAC from high-risk controls with an AUC of 100.0%, a sensitivity of 100.0% and a specificity of 100.0% at the training stage and an AUC of 89.5%, a sensitivity of 85.4% and a specificity of 83.3% at the validation stage. Another panel of five small ncRNA pair ratios (different from the first) was able to differentiate LAC from benign disease with an AUC of 82.0%, a sensitivity of 81.1% and a specificity of 78.1% in the training cohort and an AUC of 74.2%, a sensitivity of 70.4% and a specificity of 72.7% in the validation cohort.ConclusionsSeveral small ncRNA pair ratios were identified as markers capable of discerning patients with LAC from those with benign lesions or high-risk control individuals.

Highlights

  • Lung cancer is a major cause of cancer-related mortality worldwide, and around two-thirds of patients have metastasis at diagnosis

  • Small non-coding RNAs, including microRNAs, nucleolar RNAs and tRNAs, have been shown to repress or degrade specific transcripts involved in cell fate and proliferation, cell death, energy metabolism and tumorigenesis [8]

  • The list of small ncRNA pairs that apparently fulfilled all three criteria in the training stage and were candidate biomarkers for lung adenocarcinoma (LAC) are listed in Additional file 1: Table S1

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Summary

Introduction

Lung cancer is a major cause of cancer-related mortality worldwide, and around two-thirds of patients have metastasis at diagnosis. Detecting lung cancer at an early stage could reduce mortality. Aberrant levels of circulating small non-coding RNAs (small ncRNAs) are potential diagnostic or prognostic markers for lung cancer. In the USA, the incidence of lung cancer was estimated to be the second highest among all cancers (224,390 new cases in 2016), and lung cancer was predicted to be the most important cause of Detecting lung cancer at its early stages could reduce mortality rates by 10- to 50-fold [5], but about two-thirds of patients have metastasis at diagnosis. Aberrant levels of circulating miRNAs could be potential diagnostic or prognostic markers in lung [11], colorectal [12], prostate [13] and breast [14, 15] cancers

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