Invasive Lung Adenocarcinoma Research Articles

Evolutionary proteogenomic landscape from pre-invasive to invasive lung adenocarcinoma

Lung adenocarcinoma follows a stepwise progression from pre-invasive to invasive. However, there remains a knowledge gap regarding molecular events from pre-invasive to invasive. Here, we conduct a comprehensive proteogenomic analysis comprising whole-exon sequencing, RNA sequencing, and proteomic and phosphoproteomic profiling on 98 pre-invasive and 99 invasive lung adenocarcinomas. The deletion of chr4q12 contributes to the progression from pre-invasive to invasive adenocarcinoma by downregulating SPATA18, thus suppressing mitophagy and promoting cell invasion. Proteomics reveals diverse enriched pathways in normal lung tissues and pre-invasive and invasive adenocarcinoma. Proteomic analyses identify three proteomic subtypes, which represent different stages of tumor progression. We also illustrate the molecular characterization of four immune clusters, including endothelial cells, B cells, DCs, and immune depression subtype. In conclusion, this comprehensive proteogenomic study characterizes the molecular architecture and hallmarks from pre-invasive to invasive lung adenocarcinoma, guiding the way to a deeper understanding of the tumorigenesis and progression of this disease.

PMILACG Model: A Predictive Model for Identifying Invasiveness of Lung Adenocarcinoma Based on High-Resolution CT-Determined Ground Glass Nodule Features.

PMILACG Model: A Predictive Model for Identifying Invasiveness of Lung Adenocarcinoma Based on High-Resolution CT-Determined Ground Glass Nodule Features.

The value of intratumoral and peritumoral radiomics features in differentiating early-stage lung invasive adenocarcinoma (≤3 cm) subtypes.

The identification of different subtypes of early-stage lung invasive adenocarcinoma before surgery contributes to the precision treatment. Radiomics could be one of the effective and noninvasive identification methods. The value of peritumoral radiomics in predicting the subtypes of early-stage lung invasive adenocarcinoma perhaps clinically useful. This retrospective study included 937 lung adenocarcinomas which were randomly divided into the training set (n=655) and testing set (n=282) with a ratio of 7:3. This study used the univariate and multivariate analysis to choose independent clinical predictors. Radiomics features were extracted from 18 regions of interest (1 intratumoral region and 17 peritumoral regions). Independent and conjoint prediction models were constructed based on radiomics and clinical features. The performance of the models was evaluated using receiver operating characteristic (ROC) curves, accuracy (ACC), sensitivity (SEN), and specificity (SPE). Significant differences between areas under the ROC (AUCs) were estimated using in the Delong test. Patient age, smoking history, carcinoembryonic antigen (CEA), lesion location, length, width and clinic behavior were the independent predictors of differentiating early-stage lung invasive adenocarcinoma (≤3 cm) subtypes. The highest AUC value among the 19 independent models was obtained for the PTV0~+3 radiomics model with 0.849 for the training set and 0.854 for the testing set. As the peritumoral distance increased, the predictive power of the models decreased. The radiomics-clinical conjoint model was statistically significantly different from the other models in the Delong test (P<0.05). The intratumoral and peritumoral regions contained a wealth of clinical information. The diagnostic efficacy of intra-peritumoral radiomics combined clinical model was further improved, which was particularly important for preoperative staging and treatment decision-making.

IL-37 inhibits glycolysis of lung adenocarcinoma by inhibiting the expression of PFKFB3.

Aerobic glycolysis is one of the hallmarks of cancer. The metabolic phenotype of tumor cells is characterized by preferential dependence on glycolysis under aerobic conditions. Recent researchers have provided a piece of information on the effectiveness of targeting glycolysis. Thus, targeted glucose metabolism therapy is still a research hotspot. Interleukin 37 (IL-37) plays an important role in tumor development. Previous studies have found that IL-37 can inhibit the progression of lung adenocarcinoma in a variety of ways. For example, IL-37 can inhibit the migration and invasion of lung adenocarcinoma by inhibiting the interleukin 6(IL-6)/ Signal transducing activator of transcription 3(STAT3) pathway. IL-37 inhibits tumor growth by regulating RNA methylation at the M6A site of lung adenocarcinoma. It has been found that overexpression of IL-37 in macrophages can reverse the Warburg effect. The mechanism of IL-37 on glucose metabolism of tumor cells has not been studied. In research, glucose uptake and lactic acid production were inhibited in A549 cells with recombinant human IL-37(rhIL-37). Also, rhIL-37 inhibited the expression level of PFKFB3 in A549 cells. To verify whether the two aspects of rhIL-37's effects on A549 cells are related, we applied PFK15, a specific inhibitor of PFKFB3, to prove that rhIL-37 inhibits the glucose uptake and lactate production of A549 cells by inhibiting the expression of PFKFB3, and further inhibits the progression of lung adenocarcinoma.

TPI1 promotes MAPK/ERK-induced EMT, cell migration and invasion in lung adenocarcinoma.

Triosephosphate isomerase 1 (TPI1), as a widely involved glycolytic enzyme, plays a significant role in glucose metabolism and is highly expressed in various tumors. However, its role in lung adenocarcinoma (LUAD) remains incompletely understood. Through bioinformatic analysis, we identified a positive association between high expression of TPI1 and metastasis in LUAD. Western blot, RT-qPCR, wound healing assays and transwell experiments, were employed to investigate potential mechanisms. In this study, bioinformatic analysis showed that high expression of TPI1 was associated with poor prognosis in LUAD patients. We examined the expression of TPI1 in 29 paired LUAD tissues and found that TPI1 expression was higher in LUAD tissues than in paired adjacent noncancerous tissues. Meanwhile, overexpression of TPI1 promoted the epithelial-mesenchymal transition (EMT) process in LUAD cells, while silencing TPI1 weakened the EMT process. Furthermore, TPI1 was shown to regulate EMT through the MAPK/ERK signaling pathway. TPI1 promotes LUAD metastasis by activating the MAPK/ERK signaling pathway.

Systemic immune-inflammation index predicts survival in patients with resected lung invasive mucinous adenocarcinoma

BackgroundThe prognostic-related factors of lung invasive mucinous adenocarcinoma(IMA) are unclear because of its rarity. Various inflammation-based biomarkers were reported to predict the survival of malignant diseases. This study aims to explore the prognostic significance of the systemic immune-inflammation index(SII), which is calculated using absolute platelet, neutrophil, and lymphocyte counts, among patients with invasive mucinous adenocarcinoma. MethodsFrom January 2015 to December 2019, 106 patients were identified as having IMA accepted radical resection and enrolled in the retrospective study. We analyzed the overall survival and disease-free survival using the Kaplan-Meier method and log-rank test. Receiver operating characteristic curve was used to find the optimal SII cut-off values for survival. A Cox regression model was carried out for multivariable analyses. ResultsThe study cohort included 53 men and 53 women, with a mean age of 60 years (range 29 to 78 years, median 61 years). The median SII measured before surgery was 378.47 (range: 79.87–1701.97). ROC analyses revealed that the optimal cut-off values of SII was 379.43 for predicting both OS and DFS. An elevated SII (≥379.43) was observed in 52 patients (49.1 %), and was associated with younger age (P = 0.02), advanced T staging (P = 0.042), lymph node metastasis (P = 0.018) and pneumonic-type IMA (P = 0.018). Multivariable analysis showed that SII and pneumonic-type IMA were independent prognostic predictors of OS and DFS in radically resected IMA patients (P < 0.05). ConclusionHigh SII is correlated with worse outcome and can be a novel prognostic biomarker for IMA patients accepted radical surgery.

A CT-based deep learning model: visceral pleural invasion and survival prediction in clinical stage IA lung adenocarcinoma

Pathologic visceral pleural invasion (VPI) in patients with early-stage lung cancer can result in the upstaging of T1 to T2, in addition to having implications for surgical resection and prognostic outcomes. This study was designed with the goal of establishing and validating a CT-based deep learning (DL) model capable of predicting VPI status and stratifying patients based on their prognostic outcomes. In total, 2077 patients from three centers with pathologically confirmed clinical stage IA lung adenocarcinoma were enrolled. DL signatures were extracted with a 3D residual neural network. DL model was able to effectively predict VPI status. VPI predicted by the DL models, as well as pathologic VPI, was associated with shorter disease-free survival. The established deep learning signature provides a tool capable of aiding the accurate prediction of VPI in patients with clinical stage IA lung adenocarcinoma, thus enabling prognostic stratification.

Clinicopathological and computed tomography features associated with recurrence-free survival of patients with small-sized peripheral invasive lung adenocarcinoma after sublobectomy.

Sublobar resection is gradually becoming a standard treatment for small-sized (≤2 cm) peripheral non-small cell lung cancer (NSCLC), with lung adenocarcinoma (LADC) being the most frequent histologic subtype. However, the prognostic predictors for preoperatively determining whether sublobectomy is feasible for patients with early LADC have not yet been well identified. Therefore, this study aimed to investigate the clinicopathological and computed tomography (CT) features associated with the recurrence-free survival (RFS) of patients with small-sized invasive LADC (SILADC) after sublobar resection. This retrospective cohort study analyzed 107 patients with SILADC who underwent preoperative chest CT scan and sublobar resection from December 2012 to March 2019. The Kaplan-Meier survival was used to analyze the relationship between clinicopathological characteristics, preoperative chest CT findings, and RFS. The Cox proportional hazards regression was used to identify independent prognostic factors of poor RFS. For clinicopathological characteristics, RFS was shorter in patients aged ≥70 years, smokers, and those with micropapillary/solid-predominant adenocarcinomas (all P values <0.05). For preoperative CT features, RFS was shorter in patients with tumor size ≥1.4 cm, solid component size ≥1.1 cm, proportion of solid component ≥72%, solid density, spiculation, vascular convergence sign, peripheral fibrosis, and type II pleural tag (all P values <0.05). Multivariate analysis showed proportion of solid component ≥72% [hazard ratio (HR): 5.920; P=0.006; 95% confidence interval (CI): 1.686-20.794], spiculation (HR: 5.026; P=0.001; 95% CI: 2.008-12.581), and type II pleural tag (HR: 4.638; P=0.002; 95% CI: 1.773-12.136) were independent risk factors for poor prognosis in patients with SILADC after sub-lobectomy. Clinicopathological and CT characteristics are helpful for predicting the RFS of patients with SILADC after sublobar resection and can be used as an auxiliary tool for thoracic surgeons to choose the best surgical mode.

Clinical characteristics and progression of pre-/minimally invasive lung adenocarcinoma harboring ALK or RET rearrangements: a retrospective cohort study.

Patients harboring anaplastic lymphoma kinase (ALK) or rearranged during transfection (RET) rearrangements are usually diagnosed at a relatively late stage with nodal and distant metastasis, and rapid progression course of ALK/RET fusion-positive lung cancer were well-known. However, clinical characteristics and course of pre-/minimally invasive lung adenocarcinoma harboring ALK or RET fusions are poorly described. Identifying patients with gene fusions at early stage may offer surgical options that could cure those patients. We retrospectively included patients with surgically resected pre-/minimally invasive lung adenocarcinomas harboring epidermal growth factor receptor (EGFR) mutations or ALK/RET rearrangements, and further compared the patient clinical characteristics, nodule natural course, and survival outcomes. Radiological characteristics including ground-glass component, cystic airspace, pleural attachment, etc. were specially assessed for this study. EGFR (exons 18-22) was detected by Sanger sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the ALK/RET rearrangements. Lung cancer-specific survival (LCSS), relapse-free survival (RFS), and overall survival (OS) were all evaluated. Of 238 patients with pre-/minimally invasive lung adenocarcinomas, 226 patients had EGFR mutations, 7 patients had ALK fusions, and 5 patients had RET fusions. Average age at surgery was 45.3 years for ALK/RET-positive group and 52.6 years for EGFR-positive group (P=0.049). Radiologically, among the 12 patients with ALK/RET fusions, the majority of lesions (10/12) manifested as mixed ground-glass opacities (mGGOs), which was significantly more prevalent when compared with patients with EGFR mutations (83.4% vs. 24.3%, P<0.001). Moreover, a substantial proportion of cystic airspace was found in ALK/RET-positive group but not in EGFR-positive group (66.7% vs. 14.2%, P<0.001). Among four patients with ALK/RET fusions undergoing surveillance over 1 year before surgery, two of them developed rapid radiologic progression. The 5-year LCSS and RFS were 100%, 100% for ALK/RET-positive group, and 100%, 100% for EGFR-positive group, respectively. ALK/RET-positive pre-/minimally invasive lung adenocarcinomas were mostly characterized as mGGOs with cystic airspace developing rapid nodule progression, and no recurrence occurred during long-term follow-up after resection. This provides insights into proper curative surgery timing in the management of patients with gene fusions. However, these findings must be treated with caution and validated in future multi-center studies with larger sample size.

Predicting visceral pleural invasion in lung adenocarcinoma presenting as part-solid density utilizing a nomogram model combined with radiomics and clinical features.

To develop and validate a preoperative nomogram model combining the radiomics signature and clinical features for preoperative prediction of visceral pleural invasion (VPI) in lung nodules presenting as part-solid density. We retrospectively reviewed 156 patients with pathologically confirmed invasive lung adenocarcinomas after surgery from January 2016 to August 2019. The patients were split into training and validation sets by a ratio of 7:3. The radiomic features were extracted with the aid of FeAture Explorer Pro (FAE). A CT-based radiomics model was constructed to predict the presence of VPI and internally validated. Multivariable regression analysis was conducted to construct a nomogram model, and the performance of the models were evaluated with the area under the receiver operating characteristic curve (AUC) and compared with each other. The enrolled patients were split into training (n = 109) and validation sets (n = 47). A total of 806 features were extracted and the selected 10 optimal features were used in the construction of the radiomics model among the 707 stable features. The AUC of the nomogram model was 0.888 (95% CI: 0.762-0.961), which was superior to the clinical model (0.787, 95% CI: 0.643-0.893; p = 0.049) and comparable to the radiomics model (0.879, 95% CI: 0.751-0.965; p > 0.05). The nomogram model achieved a sensitivity of 90.5% and a specificity of 76.9% in the validation dataset. The nomogram model could be considered as a noninvasive method to predict VPI with either highly sensitive or highly specific diagnoses depending on clinical needs.

Transcriptomic landscape based on annotated clinical features reveals PLPP2 involvement in lipid raft-mediated proliferation signature of early-stage lung adenocarcinoma

BackgroundImage-based screening improves the detection of early-stage lung adenocarcinoma (LUAD)but also highlights the issue of high false-positive diagnoses, which puts patients at a risk of unnecessary over-treatment. Therefore, more precise discrimination criteria are required to ensure that patients with early-stage LUAD receive appropriate treatments.MethodsWe integrated 158 early-stage LUAD cases from 2 independent cohorts, including 30 matched resected specimens with complete radiological and pathological information, and 128 retrospective pathological pair-samples with partial follow-up data. This integration allowed us to conduct a correlation analysis between clinical phenotype and transcriptome landscape. Immunohistochemistry was performed using tissue microarrays to examine the expression of phospholipid phosphatase 2 (PLPP2) and lipid-raft markers. Lipidomics analysis was used to determine the changes of lipid components in PLPP2-overexpressed cells. To assess the effects of PLPP2 on the malignant phenotypes of LUAD cells, we conducted mice tumor-bearing experiments and in vitro cellular experiments by knocking down PLPP2 and inhibiting lipid raft synthesis with MβCD, respectively.ResultsBioinformatics analysis indicated that the co-occurrence of lipid raft formation and rapid cell proliferation might exhibit synergistic effects in driving oncogenesis from lung preneoplasia to adenocarcinoma. The enhanced activation of the cell cycle promoted the transition from non-invasive to invasive status in early-stage LUAD, which was related to an increase in lipid rafts within LUAD cells. PLPP2 participated in lipid raft formation by altering the component contents of lipid rafts, such as esters, sphingomyelin, and sphingosine. Furthermore, elevated PLPP2 levels were identified as an independent prognostic risk factor for LUAD patients. Further results from in vivo and in vitro experiments confirmed that PLPP2 could induce excessive cell proliferation by enhancing lipid raft formation in LUAD cells.ConclusionsOur study has revealed the characteristics of gene expression profiles in early-stage LUAD patients with the different radiological and pathological subtypes, as well as deciphered transcriptomic evolution trajectory from preneoplasia to invasive LUAD. Furthermore, it suggests that PLPP2-mediated lipid raft synthesis may be a significant biological event in the initiation of early-stage LUAD, offering a potential target for more precise diagnosis and therapy in clinical settings.

Upregulated enhancer of rudimentary homolog promotes epithelial‑mesenchymal transition and cancer cell migration in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the deadliest cancers regarding both mortality rate and number of deaths and warrants greater effort in the development of potential therapeutic targets. The enhancer of rudimentary homolog (ERH) has been implicated in the promotion and progression of certain types of cancer. In the present study, ERH was assessed for its expression pattern and survival association with LUAD in public transcriptomic and proteomic databases. Bioinformatic methods and data from websites, including University of Alabama at Birmingham CANcer data analysis Portal and The Cancer Genome Atlas, were utilized to demonstrate the functional behaviors and corresponding pathways of ERH in LUAD. Human A549 and CL1‑0 cell lines were used to validate the findings via functional assays. It was demonstrated that the expression of ERH, at both the transcriptomic and proteomic levels, was higher in LUAD compared with in adjacent non‑tumor lung tissue and was associated with worse survival prognosis. Moreover, high ERH expression was correlated with more aggressive functional states, such as cell cycle and invasion in LUAD, and the positive ERH‑correlated gene set was associated with worse survival and an immunosuppressive tumor microenvironment. Small nuclear ribonucleoprotein polypeptide G was identified as a molecule that potentially interacted with ERH. Lastly, it was demonstrated that ERH promoted epithelial‑mesenchymal transition and cell migration invitro, but not proliferation. In conclusion, higher expression of ERH in LUAD may facilitate cancer progression and confer worse outcomes. Further deep investigation into the role of ERH in LUAD is needed.

Lack of incremental value of three-dimensional measurement in assessing invasiveness for lung cancer.

The aim of this study was to evaluate the performance of consolidation-to-tumour ratio (CTR) and the radiomic models in two- and three-dimensional modalities for assessing radiological invasiveness in early-stage lung adenocarcinoma. A retrospective analysis was conducted on patients with early-stage lung adenocarcinoma from Guangdong Provincial People's Hospital and Shenzhen People's Hospital. Manual delineation of pulmonary nodules along the boundary was performed on cross-sectional images to extract radiomic features. Clinicopathological characteristics and radiomic signatures were identified in both cohorts. CTR and radiomic score for every patient were calculated. The performance of CTR and radiomic models were tested and validated in the respective cohorts. A total of 818 patients from Guangdong Provincial People's Hospital were included in the primary cohort, while 474 patients from Shenzhen People's Hospital constituted an independent validation cohort. Both CTR and radiomic score were identified as independent factors for predicting pathological invasiveness. CTR in two- and three-dimensional modalities exhibited comparable results with areas under the receiver operating characteristic curves and were demonstrated in the validation cohort (area under the curve: 0.807 vs 0.826, P = 0.059) Furthermore, both CTR in two- and three-dimensional modalities was able to stratify patients with significant relapse-free survival (P < 0.000 vs P < 0.000) and overall survival (P = 0.003 vs P = 0.001). The radiomic models in two- and three-dimensional modalities demonstrated favourable discrimination and calibration in independent cohorts (P = 0.189). Three-dimensional measurement provides no additional clinical benefit compared to two-dimensional.

Invasive FoxM1 phosphorylated by PLK1 induces the polarization of tumor-associated macrophages to promote immune escape and metastasis, amplified by IFITM1

BackgroundUnderstanding the mechanism behind immune cell plasticity in cancer metastasis is crucial for identifying key regulators. Previously we found that mitotic factors regulate epithelial-mesenchymal transition, but how these factors convert to metastatic players in the tumor microenvironment (TME) is not fully understood.MethodsThe clinical importance of mitotic factors was analyzed by heatmap analysis, a KM plot, and immunohistochemistry in lung adenocarcinoma (LUAD) patients. Immunoprecipitation, LC–MS/MS, kinase assay, and site-directed mutagenesis were performed for the interaction and phosphorylation. A tail-vein injection mouse model, Transwell-based 3D culture, microarray analysis, coculture with monocytes, and chromatin immunoprecipitation assays were used to elucidate the function of phosphorylated FoxM1 in metastasis of TME.ResultsThe phosphorylated FoxM1 at Ser25 by PLK1 acquires the reprogramming ability to stimulate the invasive traits in cancer and influence immune cell plasticity. This invasive form of p-FoxM1 upregulates the expression of IL1A/1B, VEGFA, and IL6 by direct activation, recruiting monocytes and promoting the polarization of M2d-like tumor-associated macrophages (TAMs). Upregulation of PD-L1 in LUAD having phosphomimetic FoxM1 facilitates immune evasion. In invasive LUAD with phosphomimetic FoxM1, IFITM1 is the most highly expressed through the activation of the STING-TBK1-IRF3 signaling, which enhances FoxM1-mediated signaling. Clinically, higher expression of FOXM1, PLK1, and IFITM1 is inversely correlated with the survival rate of advanced LUAD patients, providing a promising therapeutic strategy for the treatment of LUAD.ConclusionFoxM1-based therapy would be a potential therapeutic strategy for LUAD to reduce TAM polarization, immune escape, and metastasis, since FoxM1 functions as a genetic reprogramming factor reinforcing LUAD malignancy in the TME.

Discrimination of invasive lung adenocarcinoma from Lung-RADS category 2 nonsolid nodules through visual assessment: a retrospective study.

Invasive adenocarcinomas (IADs) have been identified among nonsolid nodules (NSNs) assigned as Lung Imaging Reporting and Data System (Lung-RADS) category 2. This study used visual assessment for differentiating IADs from noninvasive lesions (NILs) in this category. This retrospective study included 222 patients with 242 NSNs, which were resected after preoperative computed tomography (CT)-guided dye localization. Visual assessment was performed by using the lung and bone window (BW) settings to classify NSNs into BW-visible (BWV) and BW-invisible (BWI) NSNs. In addition, nodule size, shape, border, CT attenuation, and location were evaluated and correlated with histopathological results. Logistic regression was performed for multivariate analysis. A p value of < 0.05 was considered statistically significant. A total of 242 NSNs (mean diameter, 7.6 ± 2.8mm), including 166 (68.6%) BWV and 76 (31.4%) BWI NSNs, were included. IADs accounted for 31% (75) of the nodules. Only 4 (5.3%) IADs were identified in the BWI group and belonged to the lepidic-predominant (n = 3) and acinar-predominant (n = 1) subtypes. In univariate analysis for differentiating IADs from NILs, the nodule size, shape, CT attenuation, and visual classification exhibited statistical significance. Nodule size and visual classification were the significant predictors for IAD in multivariate analysis with logistic regression (p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value of visual classification in IAD prediction were 94.7%, 43.1%, 42.8%, and 94.7%, respectively. The window-based visual classification of NSNs is a simple and objective method to discriminate IADs from NILs. The present study shows that using the bone window to classify nonsolid nodules helps discriminate invasive adenocarcinoma from noninvasive lesions. • Evidence has shown the presence of lung adenocarcinoma in Lung-RADS category 2 nonsolid nodules. • Nonsolid nodules are classified into the bone window-visible and the bone window-invisible nonsolid nodules, and this classification differentiates invasive adenocarcinoma from noninvasive lesions. • The Lung-RADS category 2 nonsolid nodules are unlikely invasive adenocarcinoma if they show nonvisualization in the bone window.

Pathological and radiological T descriptors in invasive lung adenocarcinoma: from correlations to prognostic significance

Pathological and radiological T descriptors in invasive lung adenocarcinoma: from correlations to prognostic significance

Incidence of Lung Adenocarcinoma by Age, Sex, and Smoking Status in Taiwan.

Knowing whether the effects of smoking and other risk factors with lung adenocarcinoma (ADC) incidence varies by sex would provide information on lung cancer prevention strategies. To evaluate whether women in Taiwan have higher age- and tumor stage-specific lung ADC incidence rates than men irrespective of smoking status (ie, ever smoker or never smoker). This population-based cohort study used data sets synthesized from the Taiwan Cancer Registry (TCR) from 1979 to 2019; the TCR Long Form (TCRLF) from 2011 to 2019, which provides individual-level smoking and tumor stage information; the Taiwan Cause of Death Database (TCOD) from 1985 to 2019; the National Health Insurance Research Database (NHIRD) from 2000 to 2020; the Monthly Bulletin of Interior Statistics (MBIS) from 2011 to 2019; the National Health Interview Survey from 2001, 2005, 2009, 2013, and 2017; and Taiwan Biobank data from 2008 to 2021. Included patients were aged 40 to 84 years and had any invasive lung cancer from January 1, 2011, to December 31, 2019. Smoking status. The main outcomes were age-specific female-to-male incidence rate ratios (IRRs) of lung ADC by smoking status and tumor stage. Linked data from the TCR, TCOD, NHIRD, Taiwan National Health Interview Survey, and MBIS were used to estimate the age- and sex-specific numbers of cancer-free individuals at midyears from 2011 to 2019 by smoking status. Using the TCR and TCRLF, age-, sex-, tumor stage-, and diagnosis year-specific numbers of patients with lung ADC from 2011 to 2019 by smoking status were estimated. A total of 61 285 patients (32 599 women [53.2%]) aged 40 to 84 years (mean [SD] age, 64.66 [10.79] years) in the Taiwanese population of approximately 23 million were diagnosed with invasive lung ADC as their first lifetime cancer between 2011 and 2019. Among smokers, men had higher tobacco use by almost all examined metrics, including nearly twice the mean (SD) number of pack-years smoked (eg, 7.87 [8.30] for men aged 30-34 years vs 4.38 [5.27] for women aged 30-34 years). For 5-year age bands between 40 and 84 years, incidence of lung ADC was significantly higher among females than males for nearly all age groups irrespective of tumor stage and smoking status (eg, for the age group 70-74 years, the female-to-male IRR for late-stage lung ADC among never smokers was 1.38 [95% CI, 1.30-1.50]). In this cohort study, women had higher age- and stage-specific lung ADC incidence rates than men in Taiwan for both never and ever smokers, suggesting the possibility of differential exposures between sexes to risk factors other than smoking and the potential modification of ADC risk factors by sex. Further work is needed to determine whether this pattern replicates in other populations, discover the causes of lung ADC, and put preventive measures in place.

472P Risk of recurrence and optimal adjuvant treatment in invasive lung adenocarcinomas manifesting as radiological part-solid nodules

472P Risk of recurrence and optimal adjuvant treatment in invasive lung adenocarcinomas manifesting as radiological part-solid nodules

EP03.05-02 Genomic Landscape Features of Minimally Invasive Adenocarcinoma and Invasive Lung Adenocarcinoma

EP03.05-02 Genomic Landscape Features of Minimally Invasive Adenocarcinoma and Invasive Lung Adenocarcinoma

EP07.04-09 Pleural CEA and SUVmax as Predictors of Visceral Pleural Invasion in Clinical T1N0M0 Lung Adenocarcinoma

EP07.04-09 Pleural CEA and SUVmax as Predictors of Visceral Pleural Invasion in Clinical T1N0M0 Lung Adenocarcinoma