This study showed through retrospective case analysis that ProGRP alone can distinguish NSCLC from SCLC with an accuracy of 88.75%, while the combination of ProGRP + HE4 + NSE can accurately distinguish NSCLC from SCLC; the accuracy increased to 96.25%, suggesting that the synergistic effect of HE4 combined with other biomarkers enhances the identification of lung cancer subtypes. This evidence concerns the gene ENO2 and lung cancer.