Background: The purpose of this study was to evaluate the role of differentiation-related genes (DRGs) in tumor-associated macrophages (TAMs) in non-small cell lung cancer (NSCLC).Methods: Single cell RNA-seq (scRNA-seq) data from GEO and bulk RNA-seq data from TCGA were analyzed to identify DRGs using trajectory method. Functional gene analysis was carried out by GO/KEGG enrichment analysis. The mRNA and protein expression in human tissue were analyzed by HPA and GEPIA databases. To investigate the prognostic value of these genes, three risk score (RS) models in different pathological types of NSCLC were generated and predicted NSCLC prognosis in datasets from TCGA, UCSC and GEO databases.Results: 1,738 DRGs were identified through trajectory analysis. GO/KEGG analysis showed that these genes were predominantly related to myeloid leukocyte activation and leukocyte migration. 13 DRGs (C1QB, CCL4, CD14, CD84, FGL2, MS4A6A, NLRP3, PLEK, RNASE6, SAMSN1, SPN, TMEM176B, ZEB2) related to prognosis were obtained through univariate Cox analysis and Lasso regression. C1QB, CD84, FGL2, MS4A6A, NLRP3, PLEK, SAMSN1, SPN, and ZEB2 were downregulated in NSCLC compared to non-cancer tissue. The mRNA of 13 genes were significantly expressed in pulmonary macrophages with strong cell specificity. Meanwhile, immunohistochemical staining showed that C1QB, CCL4, SPN, CD14, NLRP3, SAMSN1, MS4A6A, TMEM176B were expressed in different degrees in lung cancer tissues. ZEB2 (HR=1.4, P<0.05) and CD14 (HR=1.6, P<0.05) expression were associated with a worse prognosis in lung squamous cell carcinoma; ZEB2 (HR=0.64, P<0.05), CD84 (HR=0.65, P<0.05), PLEK (HR=0.71, P<0.05) and FGL2 (HR=0.61, P<0.05) expression were associated with a better prognosis in lung adenocarcinoma. Three RS models based on 13 DRGs both showed that the high RS was significantly associated with poor prognosis in different pathological types of NSCLC.Conclusions: This study highlights the prognostic value of DRGs in TAMs in NSCLC patients, providing novel insights for the development of therapeutic and prognostic targets based on TAM functional differences.

The predictive value of prognosis based on the histopathological subtype is a critical criterion in the new classification of lung adenocarcinoma published in 2011 by the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), and the European Respiratory Society (ERS) (IASLC/ATS/ERS). In this new classification, the differences of histopathology and prognosis are two considerable parameters to classify the subtypes of lung adenocarcinoma. Cribriform growth pattern is regarded as a variant of acinar growth pattern in lung adenocarcinoma, however, more and more studies pointed out that cribriform growth pattern is associated with more aggressive histopathological structures, higher proportion of recurrence rates, and shorter postoperative survival than acinar growth pattern. These features are similar to solid or micropapillary predominant adenocarcinoma. In this review, we summarized the clinicopathological features, prognosis, and genetic variations of cribriform growth pattern of lung adenocarcinoma, and provided a novel insight into the diagnosis and treatment of cribriform lung adenocarcinoma.

To evaluate the feasibility and safety of sleeve lobectomy after neoadjuvant therapy by assessing the postoperative morbidity. Patients who underwent sleeve lobectomy for non-small cell lung cancer (NSCLC) were retrospectively analyzed from January 2018 to December 2021. A total of 613 patients were enrolled, including 124 patients who received previous neoadjuvant therapy and 489 patients who did not. Propensity score matching was adopted to create a balanced cohort consisting of 97 paired cases. Patient demographics and perioperative outcomes were compared between the 2 groups, and logistic regression analysis was used to identify risk factors for postoperative complications. In the entire cohort, univariable logistic regression analysis showed that smoking history (odds ratio [OR], 1.501; 95% confidence interval [CI], 1.011-2.229, P = .044), open thoracotomy (OR, 1.748; 95% CI, 1.178-2.593, P = .006), and operation time more than 150 minutes (OR, 1.548; 95% CI, 1.029-2.328, P = .036) were risk factors for postoperative complications, and multivariable logistic regression analysis showed open thoracotomy was an independent risk factor (OR, 1.765; 95% CI, 1.178-2.643, P = .006). In the balanced cohort, the neoadjuvant group had a lower proportion of double-sleeve resections (3.1% vs 11.3%, P = .035) and longer postoperative chest tube drainage (6.67 ± 3.81 vs 5.13 ± 3.74 days, P < .001). However, no significant differences were observed in postoperative morbidity between the 2 groups (25.8% vs 24.7%, P = .869). The complete pathologic response of chemoimmunotherapy was significantly superior to chemotherapy alone (28.2% vs 4.1%, P < .001), and no significant differences were noted in postoperative morbidity in different neoadjuvant therapy modalities. After neoadjuvant therapy, sleeve lobectomy can be safely performed with no increased postoperative morbidity.

Background: Visceral pleural invasion (VPI) is a clinical manifestation associated with a poor prognosis, and diagnosing it preoperatively is highly imperative for successful sublobar resection of these peripheral tumors. We evaluated the roles of computed tomography (CT) features and circulating tumor cells (CTCs) for improving VPI detection in patients with clinical T1N0M0 invasive lung adenocarcinoma. Methods: Three hundred and ninety-one patients were reviewed retrospectively in this study, of which 234 presented with a pleural tag or pleural contact on CT images. CTCs positive for the foliate receptors were enriched and analyzed prior to surgery. Logistic regression analyses were performed to assess the association of CT features and CTCs with VPI, and the receiver operating characteristic (ROC) curve was generated to compare the predictive power of these variables. Results: Patients mostly underwent either segmentectomies (18.9%) or lobectomies (79.0%). Only 49 of the 234 patients with pleural involvement on CT showed pathologically confirmed VPI. Multivariate logistic regression analysis revealed that CTC level ≥10.42 FU/3 mL was a significant VPI risk factor for invasive adenocarcinoma cases ≤30 mm [adjusted odds ratio (OR) =4.62, 95% confidence interval (CI): 2.05–10.44, P<0.001]. Based on CT features, subgroup analyses showed that the solid portion size was a statistically significant independent predictor of VPI for these peripheral nodules with pleural tag, while the solid portion length of the interface was an independent predictor of pleural contact. The receiver operating curve analyses showed that the combination of CTC and CT features were highly predictive of VPI [area under the curve (AUC) =0.921 for pleural contact and 0.862 for the pleural tag, respectively]. Conclusions: CTC, combined with CT features of pleural tag or pleural contact, could significantly improve VPI detection in invasive lung adenocarcinomas at clinical T1N0M0 stage prior to the patient’s surgery.