OBJECTIVES:The micropapillary pattern is a high-risk factor for postoperative recurrence in lung adenocarcinoma (LUAD), but the role of adjuvant chemotherapy (ACT) in stage IA LUAD with micropapillary pattern (LUADmp) after resection remains unclear. METHODS:From September 2017 to August 2020, in the phase II trial, resected stage IA LUADmp patients received ACT (pemetrexed and carboplatin), forming the ACT-group. While those meeting the trial criteria but declining ACT in the same period were designated as the SoC-group. Recurrence-free survival (RFS) was compared between groups using univariate and multivariate analyses. RESULTS:The number of patients in ACT-group and SoC-group was 81 and 75, respectively. Compared to SoC-group, patients in ACT-group were younger (60.0 years vs 64.0 years, p = 0.019), had a lower proportion of EGFR/ALK mutation (58.0% vs 78.7%, p = 0.006), and had a higher proportion of Spread Through Air Spaces (59.3% vs 40.0%, p = 0.016). At the cut-off date of January 31st 2025, the median duration of follow-up was 65.6 months. Five-year RFS in ACT-group met the prespecified primary end-point, and no significant difference was observed between ACT-group and SoC-group (ACT-group vs SoC-group: 88.9% vs 86.7%, log-rank p = 0.534). Multivariate analysis showed ACT could not predict RFS independently (HR, 0.865, 95% CI, 0.334-2.240, p = 0.765). CONCLUSIONS:ACT was not significantly associated with improved RFS for stage IA LUADmp patients postoperatively. This study was registered at ClinicalTrials.gov: NCT03351842.

Objective:The necessity of adjuvant targeted therapy in stage IB epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) remains controversial. We aimed to evaluate the efficacy of adjuvant EGFR tyrosine kinase inhibitors in patients with high-risk pathologic features and sought to explore potential subgroups that may derive benefit. Methods:This study reviewed patients with pathologic-stage IB EGFR-mutant NSCLC and high-risk factors between 2018 and 2020. Propensity score matching was used to match patients who received adjuvant EGFR tyrosine kinase inhibitors (adjuvant targeted therapy, or ATT) with those who did not (non-ATT). Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test. Results:A total of 361 patients were included, of whom 41 received ATT and 320 did not. The median follow-up was 63.6 months. In the overall cohort, post-matched DFS (hazard ratio [HR], 0.60; 95% CI, 0.31-1.17) and OS (HR, 1.06; 95% CI, 0.41-2.71) did not differ between the ATT and non-ATT groups. Multivariable analysis identified the presence of a ground-glass opacity component as a favorable prognostic factor. Subsequent subgroup analyses demonstrated that ATT significantly prolonged DFS in patients with pure-solid tumors (HR, 0.33; 95% CI, 0.12-0.92), but not OS (HR, 0.55; 95% CI, 0.13-2.28). In contrast, ATT was not associated with improved DFS or OS in patients with part-solid tumors. Conclusions:Adjuvant targeted therapy did not improve long-term survival in stage IB EGFR-mutant NSCLC with high-risk features, although it prolonged DFS in pure-solid tumors. A de-escalation strategy may be considered for postoperative management, particularly in part-solid tumors.

Background The discrepancies in clinicopathologic characteristics and prognosis between invasive mucinous adenocarcinoma (IMA) and nonmucinous lung adenocarcinoma with a mucin-laden feature (MNLA) remain unclear. Methods Data were collected retospectively for 978 consecutive patients with IMA/MNLA who underwent surgical resection between October 2017 and December 2019. Survival outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. The adjusted hazard ratio (aHR) with 95% confidence interval (CI) of the prognosticator was calculated using a multivariable Cox proportional hazards model. Results Pure IMA was associated with a higher prevalence of KRAS mutation (51.5%), while MNLA was associated with higher prevalences of EGFR mutation (40.4%) and EML4-ALK rearrangement (19.1%). Regarding prognosis, compared to patients with pure IMA, patients with MNLA or mixed IMA had worse disease-free survival (MNLA: aHR, 2.620, 95% CI, 1.690-4.061; mixed IMA: aHR, 3.458, 95% CI, 1.704-7.016) and overall survival (MNLA: aHR, 2.229, 95% CI, 1.185-4.193; mixed IMA: aHR, 1.723, 95% CI, 0.632-4.698). Among patients who experienced recurrence, those with pure IMA had a higher incidence of intrathoracic-only recurrence compared to those with MNLA (80.8% vs 39.6%), demonstrating that extrathoracic-only recurrence was more prevalent in MNLA (35.1% vs 7.3%). The recurrence pattern of mixed IMA was different from that of pure IMA (pure IMA vs mixed IMA: intrathoracic-only, 80.8% vs 50.0%; both intrathoracic and extrathoracic, 11.5% vs 40.0%). Conclusions Although MNLA, pure IMA, and mixed IMA have consistent mucin-laden features, they appear to exhibit differences in prognosis, clinicopathologic characteristics, and molecular profiles.

Neoadjuvant immunochemotherapy has transformed treatment paradigms in non-small cell lung cancer, yet its applicability in limited-disease small cell lung cancer (LD-SCLC) remains unknown. Here, we report findings from LungMate-006, the first prospective Phase II trial evaluating PD-1 blockade with tislelizumab combined with platinum-etoposide in LD-SCLC. Among 15 enrolled patients, the regimen achieved an objective response rate of 66.7% and enabled curative-intent surgery in 60% of patients, all with R0 resection. Major pathological response and pathological complete response occurred in 44.4% and 33.3% of surgical cases, respectively. Median event-free and overall survival reached 21.7 and 32.7 months. Metabolic response by PET-CT more accurately predicted pathological remission than radiographic shrinkage alone. Bulk RNA sequencing revealed a treatment-induced transition from a metabolically active baseline state toward an extracellular matrix-remodeled, CAF- and macrophage-enriched microenvironment, alongside upregulation of genes associated with tumor stemness and immune evasion. These transcriptomic changes suggest stromal-myeloid-mediated adaptive resistance in non-MPR tumors and highlight potential avenues for refining perioperative immunochemotherapy strategies in SCLC.

BACKGROUND:This study aimed to examine the risk factors for postoperative acute exacerbation (AE) and prognosis in patients with concomitant lung cancer and idiopathic pulmonary fibrosis (LC-IPF). PATIENTS AND METHODS:We retrospectively analyzed 382 patients with LC-IPF who underwent tumor resection. Clinical characteristics and outcomes were compared between patients with and without AE. Logistic regression was used to identify risk factors for AE, while Cox regression was employed to assess factors influencing overall survival (OS). RESULTS:The median age was 69.0 years (male, 87.7%). In total, 19 (5.0%) patients developed perioperative AE, with a 30-day postoperative mortality rate of 2.9%. The median follow-up time was 424 days; 67 patients experienced tumor recurrence, whereas 23 died from IPF-AE. Patients with severe IPF (> 50% of the lungs) demonstrated higher perioperative AE rates (29.4% versus 3.8%, P = 0.001). Patients who received prophylactic steroids demonstrated a lower perioperative AE incidence (6.8% versus 2.1%, P = 0.072). Univariate logistic regression revealed severe IPF and pneumonectomy as risk factors for perioperative AE, whereas prophylactic steroids was protective against AE. Multivariate Cox regression indicated that severe IPF and reduced diffusing capacity for carbon monoxide (DLCO) were associated with poorer OS, while prophylactic steroids had no significant impact on OS. CONCLUSIONS:Patients with severe IPF exhibited higher rates of perioperative AE and poorer OS. Perioperative steroid use may reduce the risk of AE but has not been associated with improved long-term outcomes. These findings highlight the need for individualized perioperative strategies in this high-risk population.

Treatment of long-segment tracheal defects (LSTDs) remains challenging, driven by the confluence of infection, oxidative stress, inflammation, and poor vascularization that compromise grafts. Here, we engineer a dual-responsive core-shell nanocapsule, co-PLGA@Cu-MSN/PP, to implement a phase-adapted paradigm for tracheal reconstruction. The inner poly(lactic-co-glycolic acid) core co-encapsulates SB431542, a transforming growth factor-beta 1 inhibitor, and Roxadustat, a hypoxia-inducible factor-1 alpha stabilizer, providing sustained anti-inflammatory and pro-angiogenic cues. The outer copper-doped mesoporous silica shell, gated by a poly(epsilon-caprolactone)-poly(ethylene glycol) copolymer, mediates pH/esterase-responsive Cu2+ release for antibacterial and antioxidative protection. The nanocapsules eradicate bacteria, attenuate ROS and pro-inflammatory cytokines, and bias macrophages toward an M2 phenotype, while concurrently enhancing pro-angiogenic functions in vitro. When embedded in acellular dermal matrix scaffolds, they support cartilaginous ring formation and yield a tubular engineered trachea with structural, biochemical and mechanical properties comparable to native trachea. In an orthotopic LSTD rabbit model, nanocapsule-loaded graft preserves airway patency, reduce infection, oxidative stress and fibrosis, enhance neovascularization and re-epithelialization, and improve survival versus controls. Transcriptomic analysis confirms coordinated activation of antibacterial, antioxidative and angiogenic pathways and suppression of MyD88-dependent toll-like receptor signaling. Collectively, this dual-responsive core-shell nanocapsule orchestrates a spatiotemporally programmed "clearance-then-repair" microenvironment for functional airway reconstruction.

Objective Part-solid nodules (PSNs) with lung adenocarcinoma (LUAD) ≤3 cm and visceral pleural invasion (VPI) are staged as T2a, yet risk stratification in this group remains unclear. We aimed to identify prognostic factors, focusing on a novel radiologic indicator—the solid-contact-length to tumor size ratio (SLTR). Method Consecutive patients with PSNs and pathologic LUAD ≤3 cm and VPI who underwent surgery from January, 2018-December, 2020 in Shanghai Pulmonary Hospital were retrospectively analyzed. SLTR was calculated from preoperative CT scans as the ratio of pleural contact length by the solid component to total tumor size and dichotomized at 0.5. Kaplan-Meier and LASSO-Cox models assessed recurrence-free survival (RFS). Discrimination was evaluated by C-index, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results Among 171 patients, 5-year RFS was 80.8% (95% CI: 74.3–88.0%). High SLTR (≥0.5) was associated with worse RFS than low SLTR (58.8% vs. 85.4%, p<0.001). In multivariable analysis, high SLTR and PL2 independently predicted recurrence; female sex was protective. Adding SLTR to a reference model including sex, histology, and VPI depth improved risk reclassification (NRI: 29.8%, p=0.040; IDI: 8.9%, p=0.020). Conclusion SLTR is an independent prognostic factor that complements VPI depth in identifying high-risk patients with part-solid LUAD and VPI. SLTR may inform postoperative risk and surveillance; its role in adjuvant-therapy selection requires prospective validation.

Background: Repairing tracheal defects remains a significant challenge in tracheal surgery. Previous attempts using traditional tissueengineered tracheal scaffolds in large animal models have largely failed due to inflammation and insufficient mechanical properties. Methods: In this study, we propose a novel approach that uses cell sheet technology to construct scaffold-free cartilage sheets in vitro. These sheets are stacked and then implanted into goats for further maturation, resulting in large neocartilage tissue with mechanical properties comparable to native tracheal cartilage. We evaluated three methods of tracheal defect repair in goat models using the stacked cartilage sheets: (1) In situ repair with stacked cartilage sheets without vascular pedicle; (2) In situ repair with stacked cartilage sheets and preservation of the vascular pedicle; (3) In situ repair with stacked cartilage sheets, preservation of the vascular pedicle, and T-tube insertion. Results: Airway stability was successfully restored in all animals, with all goats surviving until the end of the experiment without surgery-related complications. Goat 1 exhibited significant granulation tissue hyperplasia compared to goats 2 and 3. The airway morphology was best maintained in goat 3, which showed the highest degree of re-epithelialization, followed by moderate reepithelialization in goat 2, and minimal in goat 1. Conclusions: These results suggest that stacked cartilage sheets are a viable option for tracheal repair, with vascular pedicle preservation and T-tube insertion enhancing therapeutic outcomes. Our study represents the first successful use of scaffold-free cartilage sheets for tracheal repair and provides a theoretical foundation for applying this technology in tracheal reconstruction.

Background:Pneumonectomy for locally advanced non-small cell lung cancer (NSCLC) carries significant risk. While perioperative chemotherapy is standard for multimodality treatment, its specific impact on long-term survival in this high-risk surgical cohort is not well-defined. This study aims to evaluate the impact of chemotherapy on long-term survival in patients with locally advanced NSCLC undergoing pneumonectomy. Methods:Data from 640 patients with T3-4N0-3M0 NSCLC who underwent pneumonectomy were extracted from the Surveillance, Epidemiology, and End Results (SEER) database (2007-2021). Patients were grouped by chemotherapy receipt and analyzed for the timing of chemotherapy. Propensity score matching (PSM) was applied to balance baseline differences. Survival outcomes were analyzed using Cox regression and subgroup interaction analyses. Results:A total of 640 patients met the inclusion criteria, of whom 390 (60.9%) received chemotherapy. The chemotherapy group was younger, had more advanced nodal disease, and higher radiotherapy rates (all P<0.001). After PSM, 204 patients were included in each group. Compared with surgery alone, chemotherapy was associated with significantly longer overall survival (OS) (median OS: 67.0 vs. 20.0 months, P<0.001). This association remained significant even after excluding patients who died within 90 days postoperatively [log-rank P=0.002, hazard ratio (HR) =0.722, 95% confidence interval (CI): 0.588-0.886]. Furthermore, chemotherapy remained an independent protective factor in multivariate analysis (HR =0.48, 95% CI: 0.39-0.60). The difference in efficacy between adjuvant and neoadjuvant chemotherapy was not statistically significant (P=0.07, HR =1.281, 95% CI: 0.976-1.683). Subgroup analysis revealed greater survival advantages in elderly patients (≥65 years). Conclusions:Chemotherapy is associated with improved survival in locally advanced NSCLC after pneumonectomy. Neoadjuvant and adjuvant chemotherapy show comparable efficacy.

Background:Lung cancer with chronic obstructive pulmonary disease (COPD) often has a more aggressive invasion without manageable driver gene mutation. This study aimed to evaluate the safety and effectiveness of immune checkpoint blockade (ICB) in lung cancer with COPD. Methods:We searched for literature reporting immunotherapy in lung cancer with or without COPD in the PubMed, Web of Science, and Cochrane Library databases between January 2011 and July 2023. Five endpoints were evaluated: checkpoint inhibitor-related pneumonitis (CIP), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results:Eighteen studies were included. Lung cancer with COPD patients had a higher incidence of CIP (20.40% vs. 11.48%) compared to those with lung cancer without COPD (NAÏVE lung cancer), with a pooled odds ratio (OR) of 2.23 [95% confidence interval (CI): 1.48-3.37]. The ORR/DCR of lung cancer with COPD was higher than that of NAÏVE lung cancer (ORR: 32.95% vs. 20.21%, DCR: 66.51% vs. 50.83%), with pooled ORs of 2.04 (95% CI: 1.38-3.01) and 1.58 (95% CI: 1.05-2.38) for ORR and DCR, respectively. Median PFS/OS was longer in lung cancer with COPD patients than in those of NAÏVE lung cancer receiving immunotherapy, with pooled hazard ratios (HRs) of 0.57 (95% CI: 0.49-0.67) and 0.57 (95% CI: 0.47-0.68) for PFS and OS, respectively. Conclusions:This meta-analysis showed that patients of lung cancer with COPD treated with ICB achieved longer survival and better radiologic response, but had a higher risk of CIP.

Background:Pulmonary mucinous adenocarcinoma (PMA), a rare type of adenocarcinoma, remains controversial in terms of its associated prognosis. We conducted this study to compare the oncological outcomes of lobectomy and sublobectomy for peripheral small-sized PMA. Methods:This retrospective observational study included all patients with peripheral small-sized (≤2 cm) clinical stage IA1-A2 PMA who underwent lobectomy or sublobectomy (with margin distances ≥2 cm or greater than tumor diameter) between January 2015 and December 2018. Recurrence-free survival (RFS) and overall survival (OS) were compared between the lobectomy and sublobectomy groups with Kaplan-Meier curves and log-rank tests. Results:This study examined 279 patients, with 176 cases in the lobectomy group and 103 cases in the sublobectomy group. Recurrence occurred in 8 patients, and 6 patients died. Before and after propensity score matching (PSM), log-rank tests showed no statistical differences between the lobectomy and sublobectomy groups in terms of 5-year RFS (before PSM: 97.0% vs. 98.9%; after PSM: 94.6% vs. 98.9%) or 5-year OS (before PSM: 96.9% vs. 98.8%; after PSM: 94.8% vs. 98.8%), and the recurrence patterns were also similar between the two groups. The incidence of postoperative complications, such as bronchopleural fistula, hydrothorax requiring redrainage, chylothorax, respiratory failure, and pulmonary embolism, also did not differ between the two groups. Conclusions:For peripheral small-sized PMA, sublobectomy yielded an RFS and OS comparable to those of lobectomy.

Cisplatin (CDDP) combined with pemetrexed (MTA) is commonly employed in the treatment of advanced non-small cell lung cancer. However, conventional clinical administration methods fail to achieve precise spatiotemporal delivery within the tumor microenvironment (TME), resulting in inadequate control of local drug concentrations and impeding the synergistic efficacy of chemotherapeutic drugs. Aiming to address this issue, Fe2O3 hollow multi-shelled structure (HoMS) nanocarriers with spatiotemporally controlled release properties and co-encapsulated CDDP and MTA into this nanocarrier are developed. The confined microenvironment provided by Fe2O3-HoMS enables a targeted and temporal sequential drug release tailored to clinical requirements. Furthermore, chemotherapy-induced DNA damage leads to apoptosis, accompanied by a substantial generation of reactive oxygen species (ROS). The disruption of ROS homeostasis subsequently activates the ferroptosis pathway mediated by Fe2O3-HoMS. In summary, Fe2O3-HoMS exhibits a highly controlled and temporal sequential release of two chemotherapeutic drugs in TME, and the HoMS nanocarriers are further involved in the regulation of ferroptosis, realizing a triple sequential delivery system comprising CDDP-MTA-Fe2+ and thus significantly enhancing the anti-tumor efficacy against lung cancer. This study proposes a novel approach for temporal sequential drug delivery by optimizing nanocarrier design, addressing the clinical challenge of precisely controlled drug release within tumors.

OBJECTIVES:To compare the oncological outcomes of segmentectomy for non-peripheral versus peripheral small-sized non-small-cell lung cancer (NSCLC). METHODS:This retrospective observational study included patients with clinical stage IA1-A2 NSCLC who underwent segmentectomy. Patients were separated based on tumour distance index (DI, which was calculated as the ratio of the distance from the entrance of the segmental bronchus to the proximal tumour margin to the distance to the lobar pleura along the same line): non-peripheral group (DI ≤ 2/3) and peripheral group (DI > 2/3). Disease-free survival (DFS) and overall survival were compared with log-rank tests. RESULTS:850 patients were included, comprising 274 in the non-peripheral group and 576 in the peripheral group. Recurrence occurred in 68 patients (24 in the peripheral group and 44 in the non-peripheral group), and 56 patients died (22 in the peripheral group and 34 in the non-peripheral group). Log-rank tests showed no statistical differences in 5-year DFS (92.2% vs 91.2%) and 5-year overall survival (96.3% vs 93.6%) between the two groups, but higher margin recurrence occurred in the non-peripheral group. Multivariable analysis revealed that age, tumour diameter, consolidation-to-tumour ratios, pathological subtype and pathologic stage were independent risk factors for DFS. Subgroup analysis indicated that patients with a non-peripheral solid NSCLC had a worse 5-year DFS (62.1% vs 76.3%) and a higher margin recurrence rate (13.2% vs 2.0%). CONCLUSIONS:Segmentectomy for small-sized non-peripheral NSCLC could gain a comparable outcome to the peripheral, but worse DFS and higher margin recurrence occurred in the non-peripheral solid NSCLC.

BACKGROUND:Neoadjuvant immunochemotherapy (neoICT) is not currently recommended for patients with stage II-IIIB non-small cell lung cancer (NSCLC) harboring oncogenic driver mutations, especially tyrosine kinase inhibitor-sensitizing epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK). This study aimed to compare the pathologic response and survival outcomes between neoICT and neoadjuvant chemotherapy (neoChT) in patients with stage II-IIIB NSCLC harboring driver mutations beyond EGFR exon 19 deletion (19del), exon 21 L858R, and ALK rearrangement. METHODS:Patients with stage II-IIIB NSCLC harboring driver mutations (EGFR 20ins/EGFR G719X/KRAS/BRAF/c-MET/HER-2/ROS1/RET/PIK3CA) who underwent neoICT or neoChT followed by curative-intent resection were retrospectively enrolled between November 2019 and August 2023. Kaplan-Meier analysis was performed to evaluate recurrence-free survival (RFS). Multivariable Cox proportional hazards regression was used to identify factors influencing survival outcomes after propensity score matching (2:1). RESULTS:A total of 52 and 24 patients received neoICT and neoChT, respectively. Kirsten rat sarcoma virus (KRAS) mutations were detected in 67.1% (51 of 76) of patients. The major pathologic response (MPR) rates were 53.8% and 4.2%, respectively. NeoICT conferred better RFS than neoChT (2-year RFS rate: 79.5% vs 49.9%; log-rank P = .012). After matching, multivariable Cox proportional hazards regression demonstrated that neoICT was associated with improved RFS compared with neoChT (hazard ratio, 0.33; 95% CI, 0.14-0.80). Similar findings were observed in both the KRAS-mutant and non-KRAS-mutant subgroups. In the neoICT group, nonadenocarcinoma histologic features and elevated programmed cell death ligand 1 levels were correlated with higher MPR rates. CONCLUSIONS:NeoICT resulted in superior pathologic response and survival compared with neoChT in both KRAS-mutant and non-KRAS-mutant subgroups.

BACKGROUND:Low-dose computed tomography (CT) screening has increased early-stage lung cancer detection, leading to a higher demand for video-assisted thoracoscopic surgery (VATS) lobectomy. Overlapping surgeries optimize resources but raise safety concerns. This study evaluates the safety and efficiency of overlapping VATS lobectomies in a high-volume center. METHODS:We conducted a retrospective cohort study of patients undergoing VATS lobectomy at Shanghai Pulmonary Hospital, Tongji University between 2019 and 2021. Overlapping surgeries, defined as the principal surgeon involved in 2 simultaneous procedures, were stratified by percentage of overlap duration: <50% or ≥50%. Nonoverlapping cases served as the control group. Coarsened exact matching (CEM) was applied to adjust for confounders. The primary outcome was major complications (Clavien-Dindo grade III-IV). Secondary outcomes included 90-day mortality, minor complications, unplanned readmission, hospital length of stay, and intraoperative events. RESULTS:Among 14,352 patients, overlapping cases involved greater preoperative workload (median, 221 minutes vs 85 minutes; P < .001) and later operative start times (P < .001). After CEM, 3216 matched pairs showed no significant differences in major complications, mortality, readmissions, prolonged hospital stay, or minor complications. Intraoperative events (ie, operative time, bleeding, and conversion) showed only small statistical differences without clinical significance. Subgroup analyses confirmed similar outcomes regardless of overlap duration. CONCLUSIONS:When appropriately supervised, overlapping VATS lobectomies are safe, with outcomes unaffected by even ≥50% overlap, thus optimizing efficiency in high-volume centers. This practice enhances surgical efficiency in high-volume centers without compromising patient safety.

Chronic obstructive pulmonary disease (COPD) and lung cancer, frequently comorbid conditions intricately linked through smoking, represent significant global health challenges. COPD is a common comorbidity in nonsmall cell lung cancer (NSCLC) patients and has been shown to negatively impact prognosis. However, the molecular mechanisms underlying the interplay between COPD and lung cancer remain unclear. This study aims to identify differentially expressed genes (DEGs) associated with COPD-related lung cancer and, using various machine learning (ML) algorithms, uncover potential biomarkers for prognosis. We analyzed RNA sequencing data from 41 lung cancer patients (with and without COPD) and identified 61 DEGs, all of which were upregulated in solitary lung cancer compared to COPD-associated cases. Functional enrichment analysis revealed that these genes are involved in biological processes such as granulocyte chemotaxis and smooth muscle contraction and molecular functions including neuropeptide receptor binding. Three ML methods-support vector machine recursive feature elimination (SVM-RFE), least absolute shrinkage and selection operator (LASSO), and random forest-were applied to prioritize key biomarkers. Three genes, GAP43, NMU, and TEX29, were consistently selected across all methods. Further analysis demonstrated significant correlations between these genes and immune cell infiltration, with notable differences in immune cell composition observed in COPD-associated lung cancer. High expression levels of GAP43, NMU, and TEX29 were associated with poor survival outcomes in lung cancer patients, as validated through survival analysis of TCGA database data. Our findings suggest that these genes may serve as diagnostic and prognostic biomarkers for COPD-related lung cancer, thereby providing insights into potential therapeutic targets. Further studies with larger cohorts are required to validate these results and elucidate the underlying molecular mechanisms.

OBJECTIVE:The study objective was to investigate the clinicopathological characteristics and prognosis of mucin-laden nonmucinous lung adenocarcinoma. METHODS:Between October 2017 and December 2019, a total of 529 patients with nonmucinous lung adenocarcinoma who received surgical resection were retrospectively collected. Disease-free survival and overall survival were estimated by the Kaplan-Meier method and compared using the log-rank test. Adjusted hazard ratio (aHR) with 95% CI of the prognosticator was calculated by Cox proportional hazards model, and cumulative incidence function was measured by competing risk regression model. RESULTS:In the entire cohort, nearly all patients were diagnosed as intermediate (n = 301, 56.9%) or high grade (n = 225, 42.5%) according to the International Association for the Study of Lung Cancer pathologic grade system, and the most frequent mucin-distribution pattern was extracellular distribution (n = 307, 59.5%), followed by both intracytoplasmic and extracellular distribution (22.3%) and intracytoplasmic distribution (18.2%). Among different mucin-distribution patterns, tumors with extracellular mucin were associated with the most prevalent tumor of 2 to 5 cm (59.7%) and EGFR mutation (47.8%), and tumors with intracytoplasmic and extracellular mucin were associated with EML4-ALK rearrangement (37.5%). Tumors with extracellular mucin had poorer disease-free survival (aHR, 1.871, 95% CI, 1.158-3.020) and overall survival (aHR, 4.243, 95% CI, 1.618-11.125) compared with tumors with intracytoplasmic mucin. Subsequently, analysis of the recurrent pattern using competing risk regression model revealed that tumors with extracellular mucin were a predictor for distant recurrence (aHR, 2.824, 95% CI, 1.607-4.960). CONCLUSIONS:This study provided a comprehensive description of the clinicopathological characteristics and prognosis of patients with nonmucinous lung adenocarcinoma and demonstrated that mucin-distribution patterns significantly impact prognosis.

Lung squamous cell carcinoma (LUSC) represents a major subtype of lung cancer, and it demonstrates limited treatment options and worse survival. Identifications of a prognostic model and chemoresistance mechanism can be helpful for improving stratification and guiding therapy decisions. The integrative development of machine learning-based models reveals a random survival forest (RSF) prognostic model for LUSC. The 12-gene RSF model exhibits high prognostic power in more than 1,000 LUSC patients. High-risk LUSC patients are associated with worse survival and the activation of the epithelial-mesenchymal transition pathway. Additionally, high-risk LUSC patients are resistant to docetaxel or vinorelbine treatment. In vitro and in vivo drug sensitivity experiments indicates that high-risk HCC15/H226 tumour cells and cell line-derived xenograft models are more resistant to vinorelbine treatment. Furthermore, the combination of chemotherapy with transforming growth factor-β inhibition augments antitumour responses in LUSC tumours. Our study provides valuable insights into prognosis stratification and the development of therapeutic strategies for LUSC. A random survival forest prognostic model for the risk assessment of newly diagnosed LUSC patients may guide the application of chemotherapy in LUSC.