Clinical verification of plasma messenger RNA as novel noninvasive biomarker identified through bioinformatics analysis for lung cancer

Abstract

Lung cancer (LC) remains associated with significant mortality worldwide. The lack of reliable noninvasive biomarkers and targeted therapies contributes to poor survival rate. Herein, we initially took advantage of the public microarray data from Oncomine database to filter messenger RNAs (mRNAs) as potential biomarkers. Subsequently, clinical validation was applied to identify candidate noninvasive biomarkers in plasma from patients with LC. Through comprehensive analysis of transcriptional expression profiles across 12 studies, top 6 over- and underexpressed mRNAs were generated. Then, a pair of matched plasma samples from LC patient and normal control was detected by RT-PCR, and three genes with positive bands were selected for further validation. Finally, qPCR was conducted to further assess values of the three identified genes. We displayed with high confidence that two cell-free mRNAs (HJURP and ADAMTS8) were expressed at significantly levels compared to normal controls. Receiver-operating characteristic (ROC) curves on the diagnostic efficacy of plasma HJURP and ADAMTS8 mRNAs in LC diagnosis showed that the area under the ROC (AUC) was 0.6960 and 0.6877; sensitivity was 66.0% and 83.7%; specificity was 78.6% and 71.4%, respectively. Combined ROC analyses using these two biomarkers revealed an elevated AUC of 0.75. Furthermore, the higher HJURP level could be associated with early-stage LC while lower ADAMTS8 level could be correlated with non-small cell lung cancer. Collectively, circulating HJURP and ADAMTS8 mRNAs are promising noninvasive biomarkers for LC diagnosis. Our integrative strategy provides new insights into novel noninvasive biomarker identification for other types of cancer.

Potential Salivary mRNA Biomarkers for Early Detection of Oral Cancer

“…Salivary mRNA of COL3A1 also showed an opposite expression pattern in OSCC tissues (GSE13601 and GSE37991). A previous study has shown that mRNA expression trends can vary between tissue RNA and plasma circulating RNA [30]. Because the potential differences in mRNA expression between tumor tissues and saliva cannot be easily deduced, further study is needed.…”

<p>Plasma Messenger RNAs Identified Through Bioinformatics Analysis are Novel, Non-Invasive Prostate Cancer Biomarkers</p>

“…Analysis of receiver operating characteristic (ROC) curves were used to evaluate the candidate biomarker diagnostic value as previously described. 8 Differences were considered significant at P < 0.05.…”

“…Since it was first demonstrated in the 1990s by Lo et al, circulating cell-free messenger RNA has been used to detect diagnostic and prognostic biomarkers in various cancers, including lung, nasopharyngeal, and colorectal cancers. 7,8 In addition, March-Villalba et al 9 showed that plasma telomerase reverse transcriptase (hTERT) mRNA can be a useful biomarker for the diagnosis and prediction of prognosis in PCa patients. The above studies suggested that cell-free RNA in plasma may play a vital role in cancer diagnosis and prognosis.…”

“…11 Oncomine has been successfully used to initially explore novel, noninvasive biomarkers through bioinformatics analysis in lung cancer. 8 In this study, existing microarray data from PCa tissues in the Oncomine database were compared with data from normal tissues to obtain useful candidate differently expressed genes (DEGs) as potential novel, noninvasive biomarkers. Next, plasma mRNA was extracted from PCa patients and healthy donors and plasma mRNA expression of DEGs was evaluated by qRT-PCR.…”

Peer Review #1 of "Discovery of plasma messenger RNA as novel biomarker for gastric cancer identified through bioinformatics analysis and clinical validation (v0.1)"

“…The establishment of high-throughput molecular database such as microarray databases brings a new approach for biomarker identification. We have previously published an effective bioinformatics scheme to identify noninvasive biomarkers for lung cancer (Zhou et al 2017). In the present study, we applied the similar approach to explore mRNAs circulated in plasma from patients with GC as potential biomarkers.…”