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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).

Background Tumor size and consolidation‐to‐tumor ratio (CTR) are crucial for non–small cell lung cancer (NSCLC) prognosis. However, the optimal CTR cutoff remains unclear. Whether tumor size and CTR are independent prognostic factors for part‐solid NSCLC is under debate. Here, we aimed to evaluate the prognostic impacts of CTR and tumor size on NSCLC, especially on part‐solid NSCLC. Methods We reviewed 1366 clinical T1 NSCLC patients who underwent surgical treatment. Log‐rank test and Cox regression analyses were adopted for prognostic evaluation. The “surv_cutpoint” function was used to identify the optimal CTR and tumor size cutoff values. Results There were 416, 510, and 440 subjects with pure ground‐glass opacity (pGGO), part‐solid, and pure solid nodules. The 5‐year overall survival (disease‐free survival) for patients with pGGO, part‐solid, and pure solid nodules were 99.5% (99.5%), 97.3% (95.8%), and 90.4% (78.9%), respectively. Multivariate Cox regression analysis indicated that CTR was an independent prognostic factor for the whole patients, and the optimal CTR cutoff was 0.99. However, for part‐solid NSCLC, CTR was not independently associated with survival, even if categorized by the optimal cutoffs. The predicted optimal cutoffs of total tumor size and solid component size were 2.4 and 1.4 cm for part‐solid NSCLC. Total tumor size (HR = 6.21, 95% CI: 1.58–24.34, p = 0.009) and solid component size (HR = 2.27, 95% CI: 1.04–5.92, p = 0.045) grouped by the cutoffs were significantly associated with part‐solid NSCLC prognosis. Conclusions CTR was an independent prognostic factor for the whole NSCLC, but not for the part‐solid NSCLC. Tumor size was still meaningful for part‐solid NSCLC.

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