Serum human epididymis Protein-4 outperforms conventional biomarkers in the early detection of non-small cell lung cancer.

We employed a three-step approach to evaluate serum immunoassay-based biomarkers for detecting non-small cell lung cancer (NSCLC). In the first step, we performed a systematic review and meta-analysis and implemented the Laboratory Medicine Best Practices (LMBP) method to identify potential biomarkers. From potential biomarkers, Carcinoembryonic antigen (CEA), cytokeratin 19-fragments (Cyfra 21-1), and human epididymis protein-4 (HE4) were categorized as LMBP "recommend." In the second step, we conducted matched-case-control validation on these recommended biomarkers and SAA, identified as the most accurate in the first step. In the third step, a re-meta-analysis was performed by integrating our experimental results and considering covariates. The final results revealed that HE4 emerged as the most reliable biomarker, offering balanced sensitivity and specificity, with accuracy unaffected by tumor stage, making it suitable for early diagnosis. Our findings support the inclusion of HE4 in clinical guidelines for NSCLC diagnosis, alongside well-established biomarkers such as Cyfra 21-1 and CEA.