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MicroRNA Based Liquid Biopsy: The Experience of the Plasma miRNA Signature Classifier MSC for Lung Cancer Screening
Published on: October 26, 2017
Validation and target gene screening of hsa-miR-205 in lung squamous cell carcinoma
Wei Huang1, Yi Jin2, Yunfeng Yuan3
1Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
Background:
Lung cancers are classified as squamous cell carcinoma (SQ), adenocarcinoma (AC) and small cell lung carcinoma (SCLC). SQ is the major subtype of lung cancer. Currently, there are no targeted therapies for SQ due to lack of understanding its driving oncogenes. In this study, we validated an SQ specific biomarker hsa-miR-205 in Chinese patients with lung cancer and screened its candidate target genes for further functional studies to enrich knowledge in SQ target therapies.
Methods:
Quantitative reverse-transcription PCR (quantitative RT-PCR) was performed on 197 macro-dissected (cancerous cells >75%) surgical lung tissues (45 SQ, 44 AC, 54 SCLC and 54 adjacent normal tissues) to validate the expression profiles of miR-205. Furthermore, the targets of this microRNA were predicted through the gateway miRecords and mapped to lung cancer-associated pathways using the KEGG (Kyoto Encyclopedia of Genes and Genomes) database. Then quantitative RT-PCR was performed on an independent cohort of 44 snap-frozen surgical lung tissues to concurrently assess the expression profiles of miR-205 and its 52 putative targeted genes.
Results:
MicroRNA-205 yielded high diagnostic accuracy in discriminating SQ from AC with an area under the curve (AUC) of 0.985, and discriminating SQ from SCLC with an AUC of 0.978 in formalin-fixed paraffin-embedded (FFPE) surgical lung tissues. Predicted targets of miR-205 were associated with 52 key members of lung cancer signaling pathways. Ten target genes (ACSL1, AXIN2, CACNA2D2, FOXO3, PPP1R3A, PRKAG3, RUNX1, SMAD4, STK3 and TBL1XR1) were significantly down-regulated in SQ and had a strong negative correlation with miR-205, while one target gene (CDH3) was up-regulated in SQ and exhibited a strong positive correlation with miR-205.
Conclusions:
We confirmed the high diagnostic accuracy of miR-205 in discriminating SQ from AC and SCLC in Chinese patients. Moreover, we identified 11 significant target genes of miR-205 which could be used for further functional studies as the basis for the development of SQ targeted therapies.
Insights
MicroRNA-205 accurately distinguishes squamous cell carcinoma (SQ) from other lung cancers. This study identified 11 target genes of miR-205, offering potential for developing new SQ targeted therapies.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Lung cancer comprises squamous cell carcinoma (SQ), adenocarcinoma (AC), and small cell lung carcinoma (SCLC).
- SQ is a major subtype, yet lacks targeted therapies due to poorly understood oncogenes.
- This study focuses on validating hsa-miR-205 as an SQ-specific biomarker and identifying its target genes.
Purpose of the Study:
- To validate hsa-miR-205 as a diagnostic biomarker for SQ lung cancer in Chinese patients.
- To identify and characterize candidate target genes of miR-205 for potential therapeutic development.
- To enhance the understanding of molecular mechanisms driving SQ lung cancer.
Main Methods:
- Quantitative reverse-transcription PCR (qRT-PCR) was used to analyze miR-205 expression in 197 lung tissue samples (SQ, AC, SCLC, normal).
- MicroRNA target prediction was performed using miRecords, with genes mapped to lung cancer pathways via KEGG.
- Expression profiles of miR-205 and 52 putative target genes were assessed in an independent cohort of 44 lung tissues.
Main Results:
- miR-205 demonstrated high diagnostic accuracy in differentiating SQ from AC (AUC=0.985) and SCLC (AUC=0.978).
- Predicted miR-205 targets were linked to 52 key lung cancer signaling pathways.
- Eleven significant target genes (10 down-regulated, 1 up-regulated in SQ) showed strong correlations with miR-205 expression.
Conclusions:
- miR-205 is a highly accurate biomarker for distinguishing SQ lung cancer from AC and SCLC in Chinese patients.
- Eleven significant target genes of miR-205 were identified.
- These target genes provide a foundation for future functional studies and the development of targeted therapies for SQ lung cancer.

