Background: Emerging evidence has suggested that dysbiosis of the lung microbiota may be associated with the development of lung diseases. However, the interplay between the lung microbiome and lung cancer remains unclear. The aim of the present study was to evaluate and compare differences in taxonomic and derived functional profiles in the lung microbiota between lung cancer and benign pulmonary diseases. Methods: Bronchoalveolar lavage fluid (BALF) samples were collected from 32 patients with lung cancer and 22 patients with benign pulmonary diseases, and further analyzed by 16S rRNA amplicon sequencing. The obtained sequence data were deeply analyzed by bioinformatics methods. Results: A significant differentiation trend was observed between the lung cancer and control groups based on principal coordinate analysis (PCoA), while richness and evenness in the lung microbiome of lung cancer patients generally resembled those of patients with benign pulmonary diseases. Phylum TM7 and six genera (c:TM7-3, Capnocytophaga, Sediminibacterium, Gemmiger, Blautia and Oscillospira) were enriched in the lung cancer group compared with the control group (adjust P<0.05). The area under the curve (AUC) combining the microbiome with clinical tumor markers to predict lung cancer was 84.52% (95% CI: 74.06–94.97%). In addition, predicted KEGG pathways showed that the functional differences in metabolic pathways of microbiome varied with groups. Conclusions: The results indicated that differences existed in the lung microbiome of patients with lung cancer and those with benign pulmonary diseases, and some certain bacteria may have potential to predict lung cancer, though future larger-sample studies are required to validate this supposition.

The tripartite motif containing 23 (TRIM23) gene is a member of the tripartite motif (TRIM) family that participates in many pathophysiological processes. However, the role of TRIM23 in lung adenocarcinoma (LUAD) remains unclear. In the present study, TRIM23 was first screened by next‐generation sequencing between the cisplatin (DDP)‐resistant A549/DDP cell line and the parental A549 cell line, combined with integrated analysis of the Gene Expression Omnibus (GEO) data (E‐GEOD‐43493 and E‐GEOD‐43494). The expression of TRIM23 was then verified to be upregulated in the DDP‐resistant LUAD cells and tissues. The knockdown of TRIM23 expression in A549/DDP cells caused increased apoptosis, decreased IC₅₀ values of DDP, NF‐κB nuclear translocation, inhibition of cell proliferation in vitro and in vivo, inhibition of GLUT1/3 expression, glucose uptake, and lactate and ATP production. TRIM23 overexpression resulted in the opposite effects in A549 cells. In addition, the inhibition of proliferation in A549 cells caused by NF‐κB signaling inhibitor PTDC or glycolysis inhibitor 3‐BrPA could be weakened by TRIM23 overexpression. Furthermore, immunohistochemical analysis revealed that TRIM23 was upregulated in 46.1% (70/152) of LUAD cases, and elevated TRIM23 expression was correlated with high expression of NF‐κB, poor cellular differentiation, and adverse overall survival (OS) and disease‐free survival (DFS). In conclusion, our study demonstrates that TRIM23 acts as an oncogene in LUAD and promotes DDP resistance by regulating glucose metabolism via the TRIM23/NF‐κB/ GLUT1/3 axis.

The farnesoid X receptor (FXR) regulates inflammation and immune responses in a subset of immune-mediated diseases. We previously reported that FXR expression promotes tumor cell proliferation in non–small cell lung cancer (NSCLC). Here we study the relevance of FXR to the immune microenvironment of NSCLC. We found an inverse correlation between FXR and PD-L1 expression in a cohort of 408 NSCLC specimens; from this, we identified a subgroup of FXRhighPD-L1low patients. We showed that FXR downregulates PD-L1 via transrepression and other mechanisms in NSCLC. Cocultured with FXRhighPD-L1low NSCLC cell lines, effector function and proliferation of CD8+ T cell in vitro are repressed. We also detected downregulation of PD-L1 in FXR-overexpressing Lewis lung carcinoma (LLC) mouse syngeneic models, indicating an FXRhighPD-L1low subtype in which FXR suppresses tumor-infiltrating immune cells. Anti–PD-1 therapy was effective against FXRhighPD-L1low mouse LLC tumors. Altogether, our findings demonstrate an immunosuppressive role for FXR in the FXRhighPD-L1low NSCLC subtype and provide translational insights into therapeutic response in PD-L1low NSCLC patients treated with anti–PD-1. We recommend FXRhighPD-L1low as a biomarker to predict responsiveness to anti–PD-1 immunotherapy.

Background: Human BarH‐like homeobox 2 (Barx2), a homeodomain factor of the Bar family, plays a critical role in cell adhesion and cytoskeleton remodeling, and has been reported in an increasing array of tumor types except non‐small cell lung carcinoma (NSCLC). The purpose of the current study was to characterize the expression of Barx2 and assess the clinical significance of Barx2 in NSCLC.Methods: Quantitative real‐time polymerase chain reaction, immunohistochemistry and western blot analysis were used to examine mRNA and protein expression, respectively. The relationships between Barx2 expression and clinicopathological variables were analyzed. Cell Counting Kit‐8 and plate colony formation assay were used to detect cell proliferation. Transwell assay was used to examine cell migration ability. Glucose uptake, lactate, adenosine triphosphate, and lactate dehydrogenase assays were used to detect aerobic glycolysis.Results: Barx2 is downregulated in NSCLC tissues compared with para‐carcinoma. Furthermore, Barx2 expression shows a negative correlation with advanced TNM stage and a high level of Ki‐67. Survival analysis reveals that Barx2 level is an independent prognostic factor for NSCLC patients. The Barx2 (low) Ki‐67 (high) group had the worst prognosis. Furthermore, the data indicate that downregulation of Barx2 expression promotes cell proliferation, migration, and aerobic glycolysis, including increased lactate dehydrogenase activity, glucose utilization, lactate production, and decreased intracellular adenosine triphospahte level. Furthermore, Barx2 acts as a negative regulator of the canonical Wnt/β‐catenin pathway. Reactivation of Wnt/β‐catenin pathway by LiCl can reverse the inhibiting effect of Barx2.Conclusions: These findings reveal that Barx2 serving as a tumor suppressor gene could decrease cell proliferation, migration, and aerobic glycolysis through inhibiting the Wnt/β‐catenin signaling pathway, and predicts a good prognosis in NSCLC.

Background: There are many studies on neoadjuvant immunotherapy for locally advanced non‐small cell lung cancer (NSCLC) patients. Expert consensus recommends neoadjuvant immunotherapy for patients with resectable stage IB–IIIA NSCLC. However, there are few clinical studies or cases to verify this.Methods: Data were collected from all NSCLC patients who underwent surgical resection after neoadjuvant chemoimmunotherapy admitted to the Affiliated Hospital of Xuzhou Medical University and Xuzhou Central Hospital between September 2020 and April 2021. Data collected included patient information, relevant examination results, intraoperative parameters, postoperative complications, pathological changes, and 90‐day mortality.Results: In total, 25 patients achieved R0 resection. Eleven (44%) patients completed surgery by thoracotomy, and three (12%) procedures were changed from minimally invasive procedures due to dense adhesions of hilar lymph nodes, which rendered it difficult to dissect the blood vessels. Thirteen (52%) patients achieved a major pathological response (MPR) with eight (32%) of these patients having a pathological complete response (pCR). Twenty‐two (88%) patients showed radiological regression, and three (12%) patients had stable disease. The median drainage time was 8.50 (3–27) days. Thirteen (52%) postoperative complications were observed, but none were above grade 3.Conclusions: In this study, neoadjuvant chemoimmunotherapy was found to reduce tumor volume, cause pathological downstaging, and raise the surgical resection rate of patients with locally advanced NSCLC, and achieve a 100% R0 resection rate. There was an acceptable rate of postoperative complications. Thus, neoadjuvant chemoimmunotherapy is safe and practical.