Combined assay of Circulating Tumor DNA and Protein Biomarkers for early noninvasive detection and prognosis of Non-Small Cell Lung Cancer

• Published in: Journal of Cancer Vol. 12; no. 4; pp. 1258 - 1269
• Main Authors: Yin, Jian-xin, Hu, Wen-wei, Gu, Hua, Fang, Jian-min
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 2021; Ivyspring International Publisher
• Subjects: Bar codes; Biomarkers; Biopsy; Disease; DNA methylation; Genes; Genomes; Lung cancer; Medical prognosis; Medical screening; Mutation; Proteins; Research Paper; Surgery; Beijing China; United States > US; China; non-small cell lung cancer; cancer early detection; next-generation sequencing; tumor biomarkers; circulating tumor DNA
• DOI: 10.7150/jca.49647
• ISSN: 1837-9664

Early diagnosis of lung cancer is critical to curtailing cancer-related deaths. We aimed to develop a highly sensitive assay for the analysis of circulating tumor DNA (ctDNA) to detect non-small cell lung cancer (NSCLC) in the early stages. We detected and mutations in paired plasma and tumor tissue samples from 147 NSCLC patients. Of these, / ctDNA mutations and protein biomarkers were comparatively analyzed in 87 individuals. In addition, tissue samples of 20 patients were subjected to repeat multi-gene detection, and pre- and post-operative paired samples of 28 patients were subjected to multi-gene detection. Clinical information was obtained to complement the prognostic value of the combined assay results and post-operative new ctDNA mutation status. / mutations were highly consistent in ctDNA and tumor DNA. Combining the detection of and mutations in ctDNA with the detection of protein biomarkers increased cancer detection sensitivity to 74.7% (65/87). None of the healthy controls tested positive using the combined assay (100% specificity). Combined assay results independently associated with recurrence-free survival. Post-operative new ctDNA mutation status independently associated with overall survival and recurrence-free survival. The detection of ctDNA may be exploited for early diagnosis of NSCLC, as highlighted by the developed assay. Further, the combined assay results and post-operative new ctDNA mutation status are promising prognostic indicators in NSCLC patients.