Abstract:Objective To analyze the evaluation value of serum carbohydrate antigen 724 (CA724) combined with cytokeratin 19 fragment (CYFRA 21-1) in assessing N2 lymph node skip metastasis in patients with stage ⅢA-N2 non-small cell lung cancer (NSCLC).Methods The clinical data of 102 patients with stage ⅢA-N2 NSCLC admitted to Cangzhou People's Hospital from August 2022 to August 2024 were retrospectively analyzed. They were divided into the skip metastasis group (28 cases) and the non-skip metastasis group (74 cases) according to whether N2 lymph node skip metastasis occurred. The serum levels of CA724 and CYFRA 21-1 were detected and compared between the two groups. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of CA724 combined with CYFRA 21-1 for N2 lymph node skip metastasis in stage ⅢA-N2 NSCLC patients, and multivariate stepwise Logistic regression analysis was used to identify its independent influencing factors.Results There were statistically significant differences in pathological type composition, maximum tumor diameter composition, N2 metastasis station composition, EGFR mutation rate, and levels of CA125, CA724, and CYFRA 21-1 between the skip metastasis group and the non-skip metastasis group (all P < 0.05). The proportion of adenocarcinoma, proportion of maximum tumor diameter < 3 cm, proportion of single-station N2 metastasis, and EGFR mutation rate in the skip metastasis group were higher than those in the non-skip metastasis group, while the levels of CA125, CA724, and CYFRA 21-1 were lower than those in the non-skip metastasis group. At the optimal cut-off value, the area under the curve (AUC) of CA724 for predicting N2 lymph node skip metastasis in stage ⅢA-N2 NSCLC was 0.842 (95% CI: 0.792, 0.892), with a sensitivity of 89.91% (95% CI: 0.789, 1.000) and a specificity of 62.03% (95% CI: 0.510, 0.730). The AUC of CYFRA 21-1 for predicting N2 lymph node skip metastasis in stage ⅢA-N2 NSCLC was 0.855 (95% CI: 0.805, 0.905), with a sensitivity of 89.91% (95% CI: 0.789, 1.000) and a specificity of 66.74% (95% CI: 0.559, 0.775). The AUC of the combined detection of CA724 and CYFRA 21-1 for predicting N2 lymph node skip metastasis in stage ⅢA-N2 NSCLC was 0.908 (95% CI: 0.858, 0.958), with a sensitivity of 84.11% (95% CI: 0.700, 0.932) and a specificity of 88.71% (95% CI: 0.805, 0.945). Multivariate stepwise Logistic regression analysis showed that single-station N2 metastasis [O^R = 2.349 (95% CI: 1.584, 3.483) ], positive EGFR mutation [O^R = 5.275 (95% CI: 2.197, 12.669) ], low serum CA125 level [O^R = 0.413 (95% CI: 0.272, 0.628) ], low CA724 level [O^R = 0.328 (95% CI: 0.174, 0.621) ], and low CYFRA 21-1 level [O^R = 0.256 (95% CI: 0.135, 0.487) ] were all risk factors for N2 lymph node skip metastasis in stage ⅢA-N2 NSCLC (all P < 0.05).Conclusion Decreased serum levels of CA724 and CYFRA 21-1 are closely related to an increased risk of N2 lymph node skip metastasis in stage ⅢA-N2 NSCLC. Both CA724 and CYFRA 21-1 have certain predictive efficacy for the occurrence of N2 lymph node skip metastasis, and their combination can further improve the predictive efficacy.