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Abstract Background This study aims to reveal the serum tumor marker (STM) levels in lung adenocarcinoma (LUAD) histological subtypes and evaluate their values in predicting the solid and micropapillary components (SMC). Methods We retrospectively analyzed 3100 invasive LUAD patients between January 2017 and December 2020. Associations between preoperative STMs (CEA, CYFRA21‐1, CA199, CA724, NSE, AFP) and LUAD subtypes were evaluated. Multivariate regression analyses were used to determine the independent predictors. Predictive models for SMC were constructed and AUC (area under the curve) was calculated. Results CEA and CYFRA21‐1 levels differed across the LUAD histological subtypes, with the SPA (solid‐predominant adenocarcinoma) having the highest level and the LPA (lepidic‐predominant adenocarcinoma) harboring the lowest level (p

Background: This study aims to reveal the serum tumor marker (STM) levels in lung adenocarcinoma (LUAD) histological subtypes and evaluate their values in predicting the solid and micropapillary components (SMC). Methods: We retrospectively analyzed 3100 invasive LUAD patients between January 2017 and December 2020. Associations between preoperative STMs (CEA, CYFRA21‐1, CA199, CA724, NSE, AFP) and LUAD subtypes were evaluated. Multivariate regression analyses were used to determine the independent predictors. Predictive models for SMC were constructed and AUC (area under the curve) was calculated. Results: CEA and CYFRA21‐1 levels differed across the LUAD histological subtypes, with the SPA (solid‐predominant adenocarcinoma) having the highest level and the LPA (lepidic‐predominant adenocarcinoma) harboring the lowest level (p <0.001). Tumors with SMC also had higher CEA and CYFRA21‐1 levels than those absence of SMC. Gender, tumor size, CEA, Ki‐67, EGFR mutation (solid components only), and tumor differentiation were significantly independently associated with the containing of SMC. Patients were split into two data sets (training set: 2017–2019 and validation set: 2020). The model with gender and tumor size yielded an AUC of 0.723 (training set) and 0.704 (validation set) for the solid component. Combination of CEA, gender, and tumor size led to a significant increase in the predictive accuracy (training set: 0.771, p = 0.009; validation set: 0.747, p = 0.034). The AUC of the model for micropapillary component with only gender and tumor size was 0.699 and 0.711 in the training set and validation set, respectively. Integration of CEA with gender and tumor size significantly improved the predictive performance with an AUC of 0.746 (training set, p = 0.045) and 0.753 (validation set, p <0.001). Conclusion: Serum CEA and CYFRA21‐1 varied considerably according to LUAD histological subtypes. The combination of serum CEA and other factors showed prominent values in predicting the SMC. [ABSTRACT FROM AUTHOR]