BackgroundAlthough many prediction models in diagnosis of solitary pulmonary nodules (SPNs) have been developed, few are widely used in clinical practice. It is therefore imperative to identify novel biomarkers and prediction models supporting early diagnosis of SPNs. This study combined folate receptor‐positive circulating tumor cells (FR+CTC) with serum tumor biomarkers, patient demographics and clinical characteristics to develop a prediction model.MethodsA total of 898 patients with a solitary pulmonary nodule who received FR+CTC detection were randomly assigned to a training set and a validation set in a 2:1 ratio. Multivariate logistic regression was used to establish a diagnostic model to differentiate malignant and benign nodules. The receiver operating curve (ROC) and the area under the curve (AUC) were calculated to assess the diagnostic efficiency of the model.ResultsThe positive rate of FR+CTC between patients with non‐small cell lung cancer (NSCLC) and benign lung disease was significantly different in both the training and the validation dataset (p < 0.001). The FR+CTC level was significantly higher in the NSCLC group compared with that of the benign group (p < 0.001). FR+CTC (odds ratio, OR, 95% confidence interval, CI: 1.13, 1.07–1.19, p < 0.0001), age (OR, 95% CI: 1.06, 1.01–1.12, p = 0.03) and sex (OR, 95% CI: 1.07, 1.01–1.13, p = 0.01) were independent risk factors of NSCLC in patients with a solitary pulmonary nodule. The area under the curve (AUC) of FR+CTC in diagnosing NSCLC was 0.650 (95% CI, 0.587–0.713) in the training set and 0.700 (95% CI, 0.603–0.796) in the validation set, respectively. The AUC of the combined model was 0.725 (95% CI, 0.659–0.791) in the training set and 0.828 (95% CI, 0.754–0.902) in the validation set, respectively.ConclusionsWe confirmed the value of FR+CTC in diagnosing SPNs and developed a prediction model based on FR+CTC, demographic characteristics, and serum biomarkers for differential diagnosis of solitary pulmonary nodules.

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e15130 Background: Lung adenocarcinoma (LADC) with micropapillary component (MPC) is a special pathological subtype of LADC, which poses higher invasive with poor prognosis, regardless of proportion of MPC. The effectiveness of molecular targeted therapy in MPC-LADC patients is still being explored without sufficient clinical evidence. Herein, we comprehensive analyzed the genetic alterations of MPC-LADC in order to find effective potential drug-target genes and guide new therapeutic strategies. Methods: We enrolled 31 MPC-LADC patients at Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University from January 2019 to December 2020, and also randomly selected 89 non-MPC-LADC patients as a reference cohort. FFPE or fresh tumors and matched blood samples were performed for NGS-based target panel detection of at least 420 genes (range 420-638 genes), and we analyzed the genomic alterations of the genes with intersection in the above panels sequencing. Results: In our MPC-LADC cohort, the proportion of micropapillary component in 31 tumors were: 5 cases with MPC < 5%, 13 cases with MPC 5% - 20%, 10 cases with MPC ≥20% and other 3 cases unclear. The most frequently mutant genes were EGFR (61.3%, 19/31), TP53 (41.9%, 13/31), ALK (19.4%, 6/31), CTNNB1 (16.1%, 5/31), KRAS (12.9%, 4/31) and SMAD4 (12.9%, 4/31). Moreover, 90.3% (28/31) patients harbored genomic alterations in RTK/RAS/MAPK pathway, 54.8% (17/31) in cell-cycle pathway, 38.7% (12/31) in Wnt pathway, and 19.4% (6/31) in PI3K/AKT/mTOR pathway. Notably, the median age of patients with ALK fusions were younger than wild-type patients (53 vs 60 years, p < 0.05). Patients with KRAS mutations had larger tumor sizes than wild-type patients (Median: 3.4 vs 2.2 cm, p < 0.05), and their lesions are more prone to vascular invasion (p < 0.05). Compared with the reference group of non-MPC-LADC patients, three mutant genes were significantly enriched in MPC-LADC group, namely, CTNNB1 (16.1% vs 1.1%, p < 0.01), ALK (16.1% vs 2.2%, p < 0.05) and SMAD4 (12.9% vs 2.2%, p < 0.05). Finally, we obtained the date of micropapillary lung adenocarcinoma in Memorial Sloan-Kettering Cancer Center (MSK) from cBioPortal database, and survival outcome analysis displayed that EGFR mutations were significantly associated with poor overall survival (OS) (p < 0.05). Conclusions: In this study, we comprehensive revealed the genomic alterations of Chinese MPC-LADC patients and their association with clinicopathological characteristic. Several MPC-enriched genes including EGFR, ALK, KRAS, CTNNB1 and SMAD4 were identified which may be potential genetic drivers of micropapillary lung tumors and could help us to reveal distinct therapeutic avenues of MPC-LADC.