Serum peptidome signatures as diagnostic biomarkers of lung cancer: A systematic review

Early detection is a hallmark of lung cancer management. Despite extensive investigation into blood-based biomarkers for this purpose, their widespread implementation in clinical practice remains limited. The low molecular weight (LMW) peptide signatures employed by MALDI-TOF MS have been extensively employed for early lung cancer detection. However, the majority of reported discriminatory peaks have exhibited variations among different studies. To address the key question of reproducibility across studies, we performed a systematic review of published reports evaluating mass spectrometry-based peptide profiling in blood as a diagnostic tool for lung cancer. The PubMed, Embase, and Scopus databases were systematically searched for original studies reporting the discriminatory peaks retrieved from lung cancer classification models after MALDI-TOF MS analysis. A total of 14 profile studies were qualified for inclusion in the review. A high degree of methodological heterogeneity was observed among these reports, particularly in pre-analytical factors and the lung cancer classification model. Despite this variability, we revealed evidence of certain reproducible discriminatory peaks among studies that consistently correlated with the presence of lung cancer. Furthermore, we present the peptide that might potentially be a biomarker for lung cancer. Our combined analysis and recent findings suggest that this blood-based peptide profiling has considerable potential to enhance lung cancer management, especially in terms of early detection. However, we need additional prospective studies that employ standardized protocols and involve larger, independent cohorts to move this technology toward clinical implementation.