ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2021; 12(4):1258-1269. doi:10.7150/jca.49647 This issue Cite
Research Paper
Combined assay of Circulating Tumor DNA and Protein Biomarkers for early noninvasive detection and prognosis of Non-Small Cell Lung Cancer
1. School of Life Sciences and Technology, Tongji University, Shanghai, China.
2. Shanghai Tongji Hospital, Tongji University, Shanghai, China.
3. Tongji University Suzhou Institute, Suzhou, Jiangsu, China.
Abstract
Purpose: 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.
Materials and Methods: We detected EGFR and KRAS mutations in paired plasma and tumor tissue samples from 147 NSCLC patients. Of these, EGFR/KRAS 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.
Results: EGFR/KRAS mutations were highly consistent in ctDNA and tumor DNA. Combining the detection of EGFR and KRAS 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.
Conclusion: 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.
Keywords: non-small cell lung cancer, next-generation sequencing, cancer early detection, circulating tumor DNA, tumor biomarkers
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