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.

AIM: To compare the outcomes of hand-sewn (HS) and linearly stapled (LS) esophagogastric anastomosis for esophageal cancer. METHODS: Before beginning this study, a rigorous protocol was established according to the recommendations of the Cochrane Collaboration. Databases and references were searched for all randomized controlled trials and comparative clinical studies that compared LS with HS esophagogastric anastomosis for esophageal cancer. The primary outcomes compared were anastomotic leak and stricture. Subgroup analyses were performed according to site of anastomosis. RESULTS: Fifteen studies were used, comprising 3203 patients (n = 2027 LS and 1176 HS). Primary outcome analysis revealed a significant decrease in anastomotic leakage (RR = 0.51, 95%CI: 0.41-0.65; P < 0.00001) associated with LS anastomosis. A significantly reduced rate of anastomotic stricture associated with LS was also found (RR = 0.56, 95%CI: 0.49-0.64; P < 0.00001). A subgroup analysis according to the site of anastomosis revealed a significantly reduced rate of anastomotic stricture (P < 0.00001). Although there was no significant difference in the decrease in thoracic anastomotic leakage, there was a significant decrease in cervical anastomotic leakage associated with LS (P < 0.00001). CONCLUSION: This meta-analysis indicates that the LS technique contributes to a reduced rate of leakage and stricture compared with the HS method.

In this meta-analysis, we conducted a pooled analysis of clinical studies comparing Linear Stapled (LS) versus Circular Stapled (CS) esophagogastric anastomosis for esophageal cancer. According to the recommendations of the Cochrane Collaboration, we established a rigorous study protocol. We performed a systematic electronic search of the PubMed, Embase, Cochrane Library, Web of Science, and Chinese Biomedical databases as well as Chinese scientific journals to identify articles to include in our meta-analysis. The primary outcomes compared were anastomotic leak, anastomotic stricture and 3-month mortality. Five controlled trials comprising 840 patients (523 LS vs. 317 CS) were included. Primary outcomes revealed a statistically significant decrease in anastomotic strictures [risk ratio (RR): 0.26, 95 % confidence interval (CI): 0.11–0.60, P = 0.002] compared with linear stapled anastomosis. However, there were no significant differences between the two groups with respect to anastomotic leakage [risk ratio (RR): 0.80, 95 % confidence interval (CI): 0.40–1.58, P = 0.52] and 3-month mortality [risk ratio (RR): 0.94, 95 % confidence interval (CI): 0.47–1.87, P = 0.85]. There were no statistical differences in the rate of 3-month mortality or anastomotic leakage between the two groups. However, the LS method contributed to a reduced rate of anastomotic strictures. This meta-analysis may offer some specific suggestions for esophagogastric anastomosis.

Background: Abietic acid (AA) is one of the terpenoids, which are multifunctional natural compounds. It has been reported that AA possesses favorable therapeutic effects on inflammation and obesity. Method: In the present study, we determined the inhibitory effect of AA on the proliferation and growth of non-small-cell lung cancer (NSCLC) cell lines for the first time. Then, flow cytometry and Western blot analysis were applied to determine the cell apoptosis and cell cycle. Finally, surface plasmon resonance, molecular docking and molecular dynamics (MD) simulation were performed to explore the underlying molecular mechanisms. Results: In vitro experiments indicated that AA displays significant anti-proliferative, cell cycle arresting and pro-apoptotic activities. Mechanistically, AA abrogated tumor necrosis factor-α induced phosphorylation of IκB kinase (IKKα/β) (Ser176/180) and IkBα (Ser32), and inhibited the nuclear translocation of nuclear factor‐κB. Moreover, we found that the activities of AA against NSCLC cells were mediated by its IKKβ inhibition. Molecular docking and MD simulations demonstrated that the mechanism of action between AA and IKKβ was through hydrophobic interactions. Conclusion: Our data indicate that AA could be a promising lead compound for the discovery of novel IKKβ inhibitors and potential agents for the treatment of NSCLC.

Background: Chemotherapy is still the primary adjuvant strategy of cancer therapy; however, the emergence of multi-drug resistance has been a cause for concern. Autophagy has been demonstrated to have a protective role against chemotherapeutic drugs in cancer cells, and autophagy inhibition is generally considered to be a promising therapeutic strategy. However, the paucity of effective and specific autophagy inhibitors limits its application. Purpose: The objective of this study was to explore the effect of DCA, small molecular antitumor agent, on the autophagy regulation and chemosensitization in NSCLC cells. Methods: We investigated the autophagy regulation of dichloroacetate (DCA) by laser confocal microscopy and western blotting in A549 and H1975 cell lines. The MTT assay and flow cytometry was performed for explore the chemosensitization effectiveness of DCA. The results were verified with subcutaneous tumor model in nude mice and the immunohistochemistry was applied for assessing the level of cell apoptosis and autophagy in vivo post treatment. Results: We found that DCA, which exhibited antitumor properties in various carcinoma models, induced apoptosis of non-small cell lung cancer cells (NSCLC) by inhibiting cancer cell autophagy. Furthermore, Perifosine, an AKT inhibitor, can greatly weaken the capacity of inducing apoptosis by DCA. The results indicate that the AKT-mTOR pathway, a main negative regulator of autophagy, is involved in the DCA-induced inhibition of autophagy. Then, we detected the effectiveness of autophagy inhibition by DCA. When used in co-treatment with the chemotherapeutic drug paclitaxel (PTX), DCA markedly decreased cell autophagy, enhanced apoptosis and inhibited proliferation in A549 and H1975 cells. The results of the xenograft experiment demonstrate that co-treatment of PTX and DCA can significantly decrease cell proliferation in vivo and prolong the survival of mice. Conclusion: Our results suggest that DCA can inhibit cell autophagy induced by chemotherapeutics, providing a new avenue for cancer chemotherapy sensitization.

Nucleolar and spindle-associated protein 1 (NUSAP1) is a microtubule-associated protein that plays a crucial role in mitosis. Despite initial reports suggesting a potential involvement of NUSAP1 in tumor progression and malignant cell regulation, there has been no systematic analysis of its role in the tumor immune microenvironment, nor its predictive value for prognosis and immunotherapy response across different cancer types. In this study, we analyze NUSAP1 mRNA and protein expression levels in various human normal and tumor tissues, using data from TCGA, GTEx, CPTAC, HPA databases, and clinical samples. Our findings reveal that NUSAP1 is highly expressed in multiple tumor tissues across most cancer types and is primarily expressed in malignant and immune cells, according to single-cell sequencing data from the TISCH database. Prognostic analysis based on curated survival data from the TCGA database indicates that NUSAP1 expression levels can predict clinical outcomes for 26 cancer types. Furthermore, Gene Set Enrichment Analysis (GSEA) suggests that NUSAP1 promotes cell proliferation, tumor cell invasion, and regulation of anti-tumor response. Analysis of immune score, immune cell infiltration, and anti-cancer immunity cycle using ESTIMATE, TIMER, and TIP databases show that high NUSAP1 levels are associated with low CD4⁺T and NKT cell infiltration but high Th2 and MDSC infiltration, inversely correlated with antigen-presenting molecules and positively correlated with a variety of immune negative regulatory molecules. Notably, patients with melanoma, lung, and kidney cancer with high NUSAP1 expression levels have shorter survival times and lower immunotherapy response rates. Using Cmap analysis, we identify Entinostat and AACOCF3 as potential inhibitors of NUSAP1-mediated pro-oncogenic effects. In vitro and in vivo experiments further confirm that NUSAP1 knockdown significantly reduces the proliferation ability of A549 and MCF-7 cells. Overall, our study highlights the potential of NUSAP1 expression as a novel biomarker for predicting prognosis and immuno-therapeutic efficacy across different human cancers and suggests its potential for developing novel antitumor drugs or improving immunotherapy.