Detection of lung cancer with blood microRNA-21 expression levels in Chinese population

Abstract

Abstract. The analysis of molecular markers in the biological field has been proposed as a useful tool for cancer diagnosis. MicroRNAs (miRNAs) may regulate diverse biological processes and play a significant role in tumorigenesis. The potential use of blood-based miRNAs as a biomarker of cancer and as a target for therapeutics is promising. The purpose of this study was to determine whether aberrant miRNA expression can be used as a molecular marker in peripheral blood for the diagnosis of lung cancer. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to analyze the expression levels of mature microRNA-21 (miR-21). Blood samples from 20 lung cancer patients and 10 healthy individuals were collected. The data were compared for the diagnosis of lung cancer. The results demonstrated that miR-21 was present in the peripheral blood in a markedly stable form and could be detected by real-time PCR sensitively and specifically. A significant difference was observed between the lung cancer cases and controls regarding miR-21 levels in peripheral blood (1947.26±930.56 pg/ml vs. 943.42±314.12 pg/ml, P=0.005). Furthermore, the overexpression of miR-21 showed a highly discriminative receiver operating characteristic (ROC) curve profile, clearly distinguishing cancer patients from cancer-free subjects with an area under the ROC curve (AUROC) of 0.912±0.045. The detection of miR-21 expression yielded 78.80% sensitivity and 100.00% specificity in the diagnosis of lung cancer. These findings indicate that in peripheral blood miR-21 may serve as a potential molecular marker for lung cancer and provide a new approach in the diagnosis of lung cancer. IntroductionLung cancer is the leading cause of cancer death in China and worldwide (1). The five-year survival rate of lung cancer patients is 13%. A crucial reason for this is that lung cancer has often already metastasized at the time of detection, rendering the long-term prognosis as poor (2). Therefore, early diagnosis of lung cancer is a realistic approach in reducing mortality associated with lung cancer. Although advanced technology, such as computed tomography (CT), positron emission tomography (PET) and X-ray appear to be promising methods of detection, technology is not capable of precisely realizing the early detection of lung cancer. The development of diagnostic tools is necessary for the early detection of lung cancer (3,4).MicroRNAs (miRNAs) are a class of small RNAs (~21-24 nt in length) that are capable of post-transcriptionally regulating hundreds of target genes, thereby controlling a wide variety of biological processes, including cell growth, proliferation, differentiation and apoptosis (5). Furthermore, miRNA expression is involved in cancer development and progression as a tumor suppressor or oncogene (6,7). Aberrant miRNA expression as a biomarker provides a new approach to improving the accuracy of the early diagnosis of lung cancer. However, miRNA expression pattern biomarkers for disease management, personalized therapy, d...

Comparison of Serum MicroRNA21 and Tumor Markers in Diagnosis of Early Non-Small Cell Lung Cancer

“…Differing results obtained in the current study can be attributed to its smaller sample size from the meta-analysis and selectivity for only NSCLC rather than other pulmonary carcinomas. Our findings are consistent with other findings in which miR21 expression could identify individuals with lung cancer [ 27 , 28 ]. Another meta-analysis determined the value of measuring miR21 expression in serum for a variety of cancer types.…”

Diagnosing Lung Cancers through Examination of Micro-RNA Biomarkers in Blood, Plasma, Serum and Sputum: A Review and Summary of Current Literature

“…The final set of 23 circulating fluid studies include blood ( Table 2 ), serum ( Table 3 ) and plasma ( Table 4 ) investigation, ranging from 2011 to 2015. Twelve include data from China [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ], five studies include data from the USA [ 35 , 36 , 37 , 38 , 39 ], three studies include data from Italy [ 40 , 41 , 42 ], one study includes data from both China and USA [ 43 ], one study includes data from France [ 44 ], and one study includes data from Poland [ 45 ]. The number of lung cancer patients enrolled ranges from 20 to 252 and the number of control patients enrolled ranges from 10 to 870.…”

“…The number of lung cancer patients enrolled ranges from 20 to 252 and the number of control patients enrolled ranges from 10 to 870. Diagnoses were confirmed through histopathology in nineteen studies [ 23 , 24 , 25 , 26 , 28 , 29 , 30 , 31 , 32 , 33 , 35 , 36 , 38 , 39 , 40 , 41 , 43 , 44 , 45 ] and cytology in one study [ 34 ], while cytology was used in three studies in conjunction with histopathology [ 27 , 37 , 42 ]. Additionally, eleven studies used a training cohort and literature to classify their miRNAs [ 25 , 26 , 27 , 31 , 33 , 35 , 36 , 37 , 38 , 41 ] while the other studies tested specific miRNAs based on literature searches [ 23 , 24 , 28 , 29 , 30 , 31 , 32 , 34 , 39 , 40 , 42 , 44 , 45 ].…”

“…Studies by Sozzi et al [ 35 ] and Sanfiorenzo et al [ 44 ] did not report a specific miRNA but looked at large panels of miRNA. The sensitivity of using different miRNAs in circulating fluid ranges from 67% to 100%, while the specificity ranges from 66.4% to 100% [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ].…”

“…None of the studies have the recommended sample size, but Yang et al [ 34 ] had the highest with 74 cases and 52 controls. Two studies had sensitivities and specificities above the 80% cutoff, with Li et al [ 32 ] having a sensitivity of 80% and specificity of 100%, and Patnaik et al [ 39 ] have a sensitivity of 88% and specificity of 89%. With all studies using different miRNAs, there is much more exploration needed regarding measuring miRNA in whole blood when investigating lung cancer.…”