Several targeted immunotherapies have recently showed significant advances in treatment of non-small cell lung cancer (NSCLC), including antibodies and inhibitors targeting programmed death-1 (PD-1) and its ligand (PD-L1). Tumor tissue samples were prospectively collected from 183 patients with NSCLC including lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). PD-L1 expression level was measured by immunohistochemistry assay and tumor mutational burden (TMB) status was assessed by next generation sequencing. Correlations between PD-L1 expressions, TMB status with clinicopathological characteristics were analyzed. PD-L1 expression was detected in 37% of ADC group and 55% in SQCC group while all clinicopathological characteristics were found comparable between these two groups. PD-L1 expression was negatively associated with overall survival in ADC group (P < 0.0001) but not in SQCC group (P = 0.418). In consistent with PD-L1 expression level, TMB status was significantly lower in ADC subjects as compared to SQCC subjects (P = 0.024) while PD-L1 positive subgroup and TMB high subgroup shared less subjects within ADC group than SQCC group. More importantly, the combination of TMB status and PD-L1 expression successfully identified responders, who showed significant longer median overall survival than non-responders (32 months vs. 8.5 months) in ADC subjects (P < 0.0001) but not in SQCC subjects. Here we tested the hypothesis that monitoring TMB, in addition to the existing PD-L1 expression level, could represent valuable non-invasive biomarkers for the chemotherapy and targeted therapy. Further analyses are in need to further assess the prognostic value of TMB for ADC and SQCC patients receiving immunotherapy.

Background: This study investigated the clinical efficiency of enhanced recovery after surgery (ERAS) using uniportal video‐assisted thoracoscopic surgery for lung cancer.Methods: The clinical data of 83 patients with early‐stage non‐small cell lung cancer (NSCLC) at the First Affiliated Hospital of Soochow University from January 2016 to February 2017 were retrospectively analyzed. ERAS was applied to 38 patients (ERAS group), while 45 patients received conventional surgical treatment (control group). The operative duration, number of lymph nodes retrieved, blood loss, visual analogue scale (VAS), postoperative duration of chest tube placement, length of hospital stay, and postoperative complications were compared between the groups.Results: Surgeries were conducted successfully in all patients, and no mortality occurred during the perioperative period. The ERAS group had better VAS on the third postoperative day, shorter chest tube duration, and shorter length of hospital stay (P < 0.05). No differences between the groups in terms of operative duration, number of lymph nodes retrieved, blood loss, VAS on the first postoperative day, or complication rate were found (P > 0.05).Conclusions: ERAS using uniportal video‐assisted thoracoscopic surgery for NSCLC patients is safe and practicable, and could also reduce the length of hospital stay.

Understanding the stepwise progression of esophageal squamous cell carcinoma (ESCC) is crucial for developing customized strategies for early detection and optimal clinical management. Herein, we aimed to unravel the transcriptional and immunologic alterations occurring during malignant transformation and identify clinically significant biomarkers of ESCC. Digital spatial profiling (DSP) was performed on 11 patients with early-stage ESCC (pT1) to explore the transcriptional alterations in epithelial, immune cell, and non-immune cell stromal compartments across regions of distinct histology, including normal tissues, low- and high-grade dysplasia, and cancerous tissues. Furthermore, single-cell spatial transcriptomics was performed using the CosMx Spatial Molecular Imaging (SMI) system on 4 additional patients with pT1 ESCC. Immunohistochemical (IHC) analysis was performed on consecutive histological sections of 20 pT1 ESCCs. Additionally, public bulk and single-cell RNA-sequencing (scRNA-seq) datasets were analyzed, and in vitro and in vivo functional studies were conducted. Spatial transcriptional reprogramming and dynamic cell signaling pathways that determined ESCC progression were delineated. Increased infiltration of macrophages from normal tissues through dysplasia to cancerous tissues occurred. Macrophage subtypes were characterized using the scRNA-seq dataset. Cell–cell communication analysis of scRNA-seq and SMI data indicated that the migration inhibitory factor (MIF)-CD74 axis may exhibit pro-tumor interactions between macrophages and epithelial cells. DSP, SMI, and IHC data demonstrated that DTX3L expression in epithelial cells and BST2 expression in stromal cells increased gradually with ESCC progression. Functional studies demonstrated that DTX3L or BST2 knockdown inhibited ESCC proliferation and migration and decreased M2 polarization of tumor-associated macrophages. Spatial profiling comprehensively characterized the molecular and immunological hallmarks from normal tissue to ESCC, guiding the way to a deeper understanding of the tumorigenesis and progression of this disease and contributing to the prevention of ESCC. Within this exploration, we uncovered biomarkers that exhibit a robust correlation with ESCC progression, offering potential new avenues for insightful therapeutic approaches.

AMP‐activated protein kinase (AMPK) serves as a “supermetabolic regulator” that helps maintain cellular energy homeostasis. However, the role of AMPK in glucose metabolism reprogramming in lung cancer remains unclear. Here, our study shows that low AMPK expression correlates with metastasis and clinicopathologic parameters of non–small‐cell lung cancer. Low AMPK significantly enhances the Warburg effect in HBE and A549 cells, which in turn induces the expression of mesenchymal markers and enhances their invasion and migration. At the mechanistic level, low AMPK up‐regulates HK2 expression and glycolysis levels through HDAC4 and HDAC5. Collectively, our findings demonstrate that low AMPK‐induced metabolism can promote epithelial‐mesenchymal transition progression in normal bronchial epithelial cells and lung cancer cells, and increase the risk for tumour metastasis.

Background: Lung cancer is a major public health issue in most countries, including China. The expression of RelB is associated with poor prognosis in diverse cancers. However, whether RelB expression could be an indicator of poor prognosis in non‐small cell lung cancer (NSCLC) is still unclear.Methods: The expression of RelB in NSCLC tumor tissue and adjacent non‐neoplastic tissues were examined by immunohistochemistry. Chi‐square or two‐tailed Fisher's exact tests were used to analyze possible associations between qualitative clinicopathological variables and RelB expression. Kaplan–Meier analysis and a Cox regression model were employed to determine independent prognostic factors.Results: The expression of RelB was increased in tumor tissue compared with adjacent non‐neoplastic tissue in NSCLC patients. High RelB expression was significantly correlated with degree of differentiation (P = 0.023), depth of tumor invasion (P < 0.001), lymph node metastasis (P = 0.017), distant metastases (P = 0.004), and tumor node metastasis stage (P < 0.001) in patients with NSCLC. NSCLC patients with high RelB expression had significantly shorter overall survival than those with low RelB expression (P < 0.001). Our results indicate that high RelB expression is an independent prognostic factor for patients with NSCLC (P < 0.001).Conclusions: High RelB expression could provide a basis for judgment of prognosis in patients with NSCLC.