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An integromic signature for lung cancer early detection.

ABSTRACT: We previously developed three microRNAs (miRs-21, 210, and 486-5p), two long noncoding RNAs (lncRNAs) (SNHG1 and RMRP), and two fucosyltransferase (FUT) genes (FUT8 and POFUT1) as potential plasma biomarkers for lung cancer. However, the diagnostic performance of the individual panels is not sufficient to be used in the clinics. Given the heterogeneity of lung tumors developed from multifactorial molecular aberrations, we determine whether integrating the different classes of molecular biomarkers can improve diagnosis of lung cancer. By using droplet digital PCR, we analyze expression of the seven genes in plasma of a development cohort of 64 lung cancer patients and 33 cancer-free individuals. The panels of three miRNAs (miRs-21, 210, and 486-5p), two lncRNAs (SNHG1 and RMRP), and two FUTs (FUT8 and POFUT1) have a sensitivity of 81-86% and a specificity of 84-87% for diagnosis of lung cancer. From the seven genes, an integromic plasma signature comprising miR-210, SNHG1, and FUT8 is developed that produces higher sensitivity (95.45%) and specificity (96.97%) compared with the individual biomarker panels (all p<0.05). The diagnostic value of the signature was confirmed in a validation cohort of 40 lung cancer patients and 29 controls, independent of stage and histological type of lung tumor, and patients' age, sex, and smoking status (all p>0.05). The integration of the different categories of biomarkers might improve diagnosis of lung cancer.

SUBMITTER: Leng Q

PROVIDER: S-EPMC5973873 | biostudies-other | 2018 May

REPOSITORIES: biostudies-other

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An integromic signature for lung cancer early detection.

Leng Qixin Q Lin Yanli Y Zhan Min M Jiang Feng F

Oncotarget 20180515 37

We previously developed three microRNAs (miRs-21, 210, and 486-5p), two long noncoding RNAs (lncRNAs) (SNHG1 and RMRP), and two fucosyltransferase (FUT) genes (FUT8 and POFUT1) as potential plasma biomarkers for lung cancer. However, the diagnostic performance of the individual panels is not sufficient to be used in the clinics. Given the heterogeneity of lung tumors developed from multifactorial molecular aberrations, we determine whether integrating the different classes of molecular biomarker ...[more]

PMID: 29872497

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Project description:BackgroundLung cancer is the second most common and the most fatal form of cancer. Although annual low-dose computed tomography is used as the primary method of cancer screening, it presents challenges regarding resources as well as potential health risks from radiation exposure. Chest radiography (CXR), though less effective, is used frequently and commonly. Moreover, often in clinical settings, CXR is the first imaging modality used; computed tomography is subsequently performed if abnormalities are detected on CXRs. This study examined whether controlling for distractors and time constraints, as well as side-by-side comparison of multiple CXRs in clinical settings can aid earlier detection of radiological abnormalities indicative of lung cancer lesions.MethodsThirty-two attending physicians in the Republic of Korea examined 1,750 radiographs of 50 lung cancer cases. Using "hot spot" technology, participants indicated the possible locations of cancer lesions on each radiograph. Subsequently, the same radiographs, cropped to focus the anatomical regions where lung cancers were diagnosed, were shown side-by-side to the participants. The participants were asked to identify the radiograph which first enabled the diagnosis of lung cancer and which first showed a possible lesion.ResultsRemoval of systemic constraints alone significantly improved lesion identification by 221.72±9.69 days. Presenting radiographs side-by-side, cropped to relevant areas, had an additional significant and positive impact on cancer detection in both hidden and open areas on CXRs. Also, lesions were detected at smaller sizes and earlier than when actually diagnosed.ConclusionsCXR with improved methods and settings provides an easily accessible and low-risk imaging method for earlier detection of lung cancer compared to current clinical imaging settings. Further, this study demonstrates the potential effectiveness of programs that allow side-by-side comparisons of cropped areas of multiple radiographs to detect radiological abnormalities.

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An integromic signature for lung cancer early detection.

Publications

An integromic signature for lung cancer early detection.

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