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

Abstract

<b>Purpose:</b> 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. <b>Materials and Methods:</b> We detected <i>EGFR</i> and <i>KRAS</i> mutations in paired plasma and tumor tissue samples from 147 NSCLC patients. Of these, <i>EGFR</i>/<i>KRAS</i> 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. <b>Results:</b> <i>EGFR</i>/<i>KRAS</i> mutations were highly consistent in ctDNA and tumor DNA. Combining the detection of <i>EGFR</i> and <i>KRAS</i> 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. <b>Conclusion:</b> 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.