Optimizing perioperative treatment for potentially resectable stage III squamous cell lung carcinoma: promising results of a condensed four-cycle regimen with tislelizumaband chemotherapy.

BACKGROUND: The standard care for resectable non-small cell lung cancer (NSCLC) involves perioperative therapy combining chemotherapy and immune checkpoint inhibitors, typically lasting 6 to 12 months. However, the optimal treatment strategies for potentially resectable squamous cell lung carcinoma (SCC) remain unclear. This Phase 2 trial aimed to assess the efficacy and safety of a condensed four-cycle perioperative treatment regimen with tislelizumab combined with chemotherapy in patients with potentially resectable stage III SCC. METHODS: Patients with potentially resectable stage IIIA-IIIB (N2) SCC received intravenous tislelizumab, albumin-bound paclitaxel, and carboplatin for up to four cycles. The primary endpoints were major pathologic response (MPR) and incidence of treatment-related adverse events. Safety and potential biomarkers for efficacy prediction were also assessed. RESULTS: Among 35 enrolled patients, 32 underwent surgery with R0 resection achieved in all cases. MPR was achieved in 24 patients and pathological complete response (pCR) in 14 patients. Radiographic objective response was observed in 31 patients. The 12-month and 24-month event-free survival rate was 85.7 and 61.0%, respectively. Four patients experienced grade 3 or 4 adverse events. Tumor tissue based next-generation sequencing revealed the potential associations between several biomarkers and pathological response, including tumor neoantigen burden score, 18-gene expression profile score, CD8 + T cells, M1/M2 macrophages ratio and interferon-gamma expression level. Besides, circulating tumor DNA (ctDNA) dynamics and concentration were also associated with pathological response and the presence of ctDNA at postoperative month 1 was a strong predictor for disease relapse. Furthermore, metagenomic sequencing in bronchoalveolar lavage fluid demonstrated Streptococcus was the most abundant genus in the pCR group. CONCLUSIONS: A condensed four-cycle perioperative treatment regimen of tislelizumab combined with chemotherapy demonstrated promising efficacy and manageable toxicities in potentially resectable stage III SCC. Specific biomarkers showed potential for predicting treatment efficacy and the mechanism of superior antitumor response of pCR patients was preliminarily and indirectly explored. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05024266. Registered August 27, 2021.

The predictive value of computed tomography value on high-resolution images in differentiating invasive from indolent lung adenocarcinoma.

Background: Invasive adenocarcinoma (IA) has a worse prognosis and different clinical management strategies compared to indolent lung adenocarcinoma including adenocarcinoma in situ (AIS) and minimally IA (MIA). The purpose of this study was to evaluate the predictive value of computed tomography (CT) value in differentiating invasive from indolent lung adenocarcinoma. Methods: The pathological diagnoses and imaging data of confirmed lung adenocarcinomas manifested as lung nodules with homogeneous internal density which were surgically resected between August 2021 and July 2022 were retrospectively analyzed. Differences in CT values between invasive and indolent lung adenocarcinomas were compared in the primary cohort (n=766), and receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off value. The predictive performance of the cut-off value was evaluated in the validation cohort (n=341). Results: A total of 1,107 lung nodules from 1,014 patients were included in the total cohort. The CT values had a significant difference between invasive and indolent lung adenocarcinomas (P<0.001). Using the primary cohort, we determined the optimal cut-off value of -415 Hounsfield units (HU) of the CT value based on ROC curve, which showed good discrimination between IA and AIS/MIA in both the primary and validation cohorts (sensitivity, 85.98% and 87.42%, specificity, 87.67% and 84.74%, respectively). Conclusions: The CT value of >-415 HU could be an effective predictor of invasive lung adenocarcinoma, thereby providing an appropriate clinical decision guide.

Cell-free DNA methylation profile potential in the diagnosis of lung squamous cell carcinoma.

Background: Aberrant methylation plays an essential role in early cancer development. In this study, we investigated methylation patterns in lung squamous cell carcinoma (LUSC) and matched non-tumor tissue and plasma samples to evaluate the potential of these patterns in the diagnosis of LUSC. Methods: The study group included 49 patients with stage I-III LUSC. We collected resected tumor tissue, paired peritumoral tissue, distant normal tissue, and corresponding plasma samples. A bespoke lung cancer bisulfite sequencing panel was used to profile the methylation level. Another 48 healthy volunteers provided control plasma samples. Results: Peritumoral and distant normal tissues presented similar methylation signatures, distinct from those in tumor tissue samples. A comparison of methylation profiles led to the identification of 871 tumor-specific differentially methylated blocks, including 847 hypermethylated and 24 hypomethylated blocks (adjusted P value <0.05). All top-ranked blocks were tumor-related. Tissue samples were analyzed for field cancerization to identify progressively aggravating aberrant methylations during tumor initiation and development. The analysis revealed that 221 blocks presented a stepwise increase in methylation levels, while seven blocks presented a stepwise decrease in methylation pattern as the sampling drew nearer to the tumor. The malignant contaminated ratio (MCR) confirmed the presence of distinct methylation patterns between tumor and peritumoral tissue samples. We then constructed a diagnostic panel using a combined diagnostic score of cell-free DNA (cfDNA) that showed high sensitivity and specificity. The healthy controls had a significantly lower combined diagnostic score (cd-score) than LUSC patients. Additionally, based on the methylation profiles, LUSC could be classified into two subgroups, C1 and C2. The methylation profile of the C2 group was not distinct from the healthy controls, which had a significantly lower cd-score than did the C1 group. Conclusions: LUSC-specific methylation patterns could potentially discriminate between peritumoral tissue, distant normal tumor tissue, and tumor tissues. This preliminary study also supported the potential utility of cfDNA methylation analysis in diagnosing LUSC.

Neo-adjuvant chemotherapy plus immunotherapy in resectable N1/N2 NSCLC.

BACKGROUND: Locally advanced non-small cell lung cancer (NSCLC) with N1/N2 lymph node metastasis is challenging with poor survival. Neo-adjuvant chemo-immunotherapy has gained benefits in a proportion of these patients. However no specific biomarker has been proved to predict the effect before therapy. In addition, the relationship of nodal status and survival after neo-adjuvant chemo-immunotherapy is still not well stated. METHODS: A total of 75 resectable NSCLC patients with N1/N2 stage who received neo-adjuvant chemo-immunotherapy plus surgery were retrospectively studied. The clinical characteristics, surgical information and safety parameters were collected. The correlations of major pathological response (MPR) and pathological complete response (pCR) with clinical data were analyzed. The progression free disease(PFS) and overall survival(OS) were evaluated with pathological response and nodal status. RESULTS: Of the 75 patients, 69 (92%) patients experienced treatment related adverse effects, while grade 3-4 adverse effects occurred in 8 (10%) patients. All the patients received surgical R0 resection with a MPR rate of 60% and a pCR rate of 36%. 67% of N1 patients and 77% of N2 patients had nodal clearance after neo-adjuvant treatment. A significant difference was observed between pathological response with age, histology and multiple lymph node metastasis. The PFS was better in the MPR cohort. The PFS was 90.1% and 83.6% at the nodal clearance group at the time of 12 and 18 months, compared with 70.1% and 63.7% at the nodal residual group. CONCLUSIONS: The neo-adjuvant chemo-immunotherapy for locally advanced NSCLC with nodal positive was safe and feasible. The patients with elder age and squamous-cell carcinoma (SCC) were more likely to have better pathological response, while multiple nodal metastasis was a negative predictor. The clearance of lymph node resulted in significantly longer PFS and OS.

Risk factors for postoperative cerebral infarction in patients after lung resection: a single-center case-control study.

Background: Patients who undergo lung resection are at risk of postoperative cerebral infarction, but the risk factors remain unclear, so the present study was a comprehensive investigation in patients who underwent lung resection for pulmonary nodules. Methods: The clinical characteristics of patients with postoperative cerebral infarction and patients who underwent lung resection on the same day but did not develop cerebral infarction were retrospectively compared. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors for cerebral infarction after lung resection. Results: A total of 22 patients with postoperative cerebral infarction and 316 controls were included. Multivariate logistic regression analysis revealed that a history of cerebral infarction [odds ratio (OR), 7.289; P=0.030], activated partial thromboplastin time (APTT) <26.5 s (OR, 3.704; P=0.018), body mass index (BMI) ≥24.0 kg/m2 (OR, 3.656; P=0.015), and surgical method (P=0.005) were independent risk factors for cerebral infarction after lung resection. Compared with patients undergoing lobectomy, the risk for postoperative cerebral infarction was significantly increased in patients undergoing segmentectomy (OR, 24.322; P=0.001), wedge resection (OR, 6.992; P=0.018), or combined surgical approach (OR, 29.921; P=0.028). Conclusions: A history of cerebral infarction, APTT <26.5 s, BMI ≥24.0 kg/m2, and surgical method were independent risk factors for cerebral infarction after lung resection. Strengthening thromboprophylaxis in patients with these risk factors may help to reduce the incidence of postoperative cerebral infarction.

Identification of a three-gene expression signature and construction of a prognostic nomogram predicting overall survival in lung adenocarcinoma based on TCGA and GEO databases.

Background: Lung adenocarcinoma (LUAD) is the major cause of cancer mortality. Traditional prognostic factors have limited importance after including other parameters. Thus, developing a more credible prognostic model combined with genes and clinical parameters is necessary. Methods: The messenger RNA (mRNA) expression and clinical information from The Cancer Genome Atlas (TCGA)-LUAD datasets and microarray data from three Gene Expression Omnibus (GEO) databases were obtained. We identified differentially-expressed genes (DEGs) between lung tumor and normal tissues through integrated analysis of the three GEO datasets. Univariate and multivariate Cox regression analyses were conducted to select survival-associated DEGs and to establish a prognostic gene signature which was associated with overall survival (OS). The expression of gene proteins was assessed in 180 LUAD tissue microarrays (TMAs) by immunohistochemistry (IHC). We verified its predictive performance with a Kaplan-Meier (KM) curve, receiver operating characteristic (ROC) curve, and Harrell's concordance index (C-index) and validated it in external GEO databases. Multivariate Cox regression analysis was performed to identify the significant prognostic indicators in LUAD. Furthermore, we established a prognostic nomogram based on TCGA-LUAD dataset. Results: A three-gene signature was constructed to predict the OS of LUAD patients. The KM analysis, ROC curve, and C-index present a good predictive ability of the gene signature in TCGA dataset [P<0.0001; C-index 0.6375; 95% confidence interval (CI): 0.5632-0.7118; area under the ROC curve (AUC) 0.674] and the external GEO datasets (P=0.05, 0.004, and 0.04, respectively). Univariate and multivariate Cox regression analyses also verified that LUAD patients with low-risk scores had a decreased risk of death compared to those with a high-risk score in TCGA database [hazard ratio (HR) =0.3898; 95% CI: 0.1938-0.7842; P<0.05]. Finally, we constructed a nomogram integrating the gene signature and clinicopathological parameters (P<0.0001; C-index 0.762; 95% CI: 0.714-0.845; AUC 0.8136). Compared with conventional staging, a nomogram can effectively improve prognosis prediction. Conclusions: The nomogram is closely associated to the OS of LUAD patients. This consequence may be beneficial to individualized treatment and clinical decision-making.

Effects of 24-hour postoperative intravenous fluid on postoperative outcomes after lobectomy: a retrospective observational study.

Background: Postoperative fluid management plays a key role in providing adequate tissue perfusion, stabilizing hemodynamics, and reducing morbidities related to hemodynamics. This study evaluated the dose-response relationship between postoperative 24-hour intravenous fluid volume and postoperative outcomes in patients with non-small cell lung cancer (NSCLC) undergoing video-assisted thoracoscopic surgery (VATS) lobectomy. Methods: A retrospective analysis of adult patients with NSCLC undergoing VATS lobectomy between May 2016 and April 2017 was performed. The primary exposure variable was total intravenous crystalloid infusion in the 24-hour postoperative period. The observation outcomes were postoperative pulmonary complications, acute kidney injury (AKI), in-hospital mortality, readmission within 30 days, prolonged hospital stay, postoperative length of stay, and total hospital care costs. Univariate and multivariate analyses were performed. Results: Of the 563 patients, 136 (24.2%) with pulmonary complications were observed. Binary logistics regression showed that, relative to the group with moderate postoperative 24-hour crystalloid infusion, the risk for postoperative pulmonary complications was significantly increased in the restrictive [odds ratio (OR) 1.815, 95% CI: 1.083-3.043; P=0.024] and liberal (OR 2.692, 95% CI: 1.684-4.305; P<0.001) groups. Conclusions: In patients with NSCLC undergoing VATS lobectomy, both restrictive and liberal 24-hour postoperative crystalloid infusions were related to adverse effects on postoperative outcomes and the optimal volume of 24-hour postoperative intravenous crystalloid infusion was 1,080-<1,410 mL.

Trends in population mortality rates in the United States from 1969 to 2017.

BACKGROUND: Fundamental transformations in overall population health have occurred in the past five decades and are continuing. Our aim in this study was to characterize the trends in population mortality rates in the United States (U.S.) from 1969 to 2017. METHODS: Data on the 109,836,044 deaths registered in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed by sex, race and ethnicity, and age. Temporal trends in population mortality rates were examined from 1969 to 2017. All data analyses were performed using the SEER*Stat software. RESULTS: The overall mortality rate for males and females in the U.S. per 100,000 population fell by 46.1% and 39.3%, from 1,610.0 and 1,019.3 in 1969 to 867.2 and 619.2 in 2017, respectively. This decline in overall mortality was mainly attributable to a decrease in mortality caused by heart and cerebrovascular diseases. From 1969 to 2017, the overall mortality rate was higher in males than females, and in blacks than whites for both sexes. From 1979 to 2017, the mortality rates of heart diseases, cerebrovascular diseases, and diabetes were all higher in blacks than in whites for both sexes. CONCLUSIONS: The results indicate that the U.S. has dramatically reduced its overall annual mortality rate between 1969 and 2017; however, the disparities among different races are still apparent.

VIRMA contributes to non-small cell lung cancer progression via N6-methyladenosine-dependent DAPK3 post-transcriptional modification.

N6-methyladenosine (m6A) has been reported to be abnormally expressed in non-small cell lung cancer (NSCLC), and plays a vital role in regulation of cell proliferation, invasion and metastasis. Vir-Like m6A methyltransferase associated (VIRMA, also called KIAA1429) has not been well studied in NSCLC. Thus, in this study, we investigated the biological impact and underlying mechanism of VIRMA in NSCLC. High expression of VIRMA was testified in patients with NSCLC and predicted worse prognosis in patients. VIRMA facilitated cell proliferation and tumor growth both in vitro and in vivo. Furthermore, VIRMA-regulated m6A modifications led to post-transcriptional suppression of death-associated protein kinase 3 (DAPK3, also called ZIP or ZIPK) through the YT521-B homology domain-containing family proteins 2/3(YTHDF2/3). Inhibition of DAPK3 rescued the tumor-suppressive phenotypes induced by VIRMA deficiency. In conclusion, VIRMA-guided m6A modifications promoted NSCLC progression via m6A-dependent degradation of DAPK3 mRNA. Therefore, VIRMA may be a novel therapeutic target in NSCLC.

Identification of key pathways and core genes involved in atherosclerotic plaque progression.

BACKGROUND: Atherosclerosis leads to the occurrence of cardiovascular diseases. However, the molecular mechanisms that contribute to atherosclerotic plaque rupture are incompletely characterized. We aimed to identify the genes related to atherosclerotic plaque progression that could serve as novel biomarkers and interventional targets for plaque progression. METHODS: The datasets of GSE28829 in early vs. advanced atherosclerotic plaques and those of GSE41571 in stable vs. ruptured plaques from Gene Expression Omnibus (GEO) were analyzed by using bioinformatics methods. In addition, we used quantitative reverse transcription polymerase chain reaction (qRT-PCR) to verify the expression level of core genes in a mouse atherosclerosis model. RESULTS: There were 29 common differentially expressed genes (DEGs) between the GSE28829 and GSE41571 datasets, and the DEGs were mainly enriched in the chemokine signaling pathway and the Staphylococcus aureus infection pathway (P<0.05). We identified 6 core genes (FPR3, CCL18, MS4A4A, CXCR4, CXCL2, and C1QB) in the protein-protein interaction (PPI) network, 3 of which (CXCR4, CXCL2, and CCL18) were markedly enriched in the chemokine signaling pathway. qRT-PCR analysis showed that the messenger RNA levels of two core genes (CXCR4 and CXCL2) increased significantly during plaque progression in the mouse atherosclerosis model. CONCLUSIONS: In summary, bioinformatics techniques proved useful for the screening and identification of novel biomarkers of disease. A total of 29 DEGs and 6 core genes were linked to atherosclerotic plaque progression, in particular the CXCR4 and CXCL2 genes.

Effects of preoperative pulmonary function on short-term outcomes and overall survival after video-assisted thoracic surgery lobectomy.

BACKGROUND: Preoperative pulmonary function tests are a necessary preoperative assessment tool for non-small cell lung cancer (NSCLC) patients awaiting surgery. We studied the effects of preoperative pulmonary function on short-term outcomes and overall survival (OS). METHODS: A retrospective cohort study was undertaken with adult NSCLC patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy between May 2016 and April 2017. The primary exposure variables were the percentage of predicted peak expiratory flow (PEF%), the percentage of predicted forced vital capacity (FVC%), and the percentage of predicted forced expiratory volume in 1 s. The observation outcomes were postoperative pulmonary complications (PPCs), acute kidney injury (AKI), in-hospital mortality, readmission within 30 days, and OS. Univariate and multivariate analyses were performed. RESULTS: Of the 548 patients, postoperative pneumonia was observed in 206 (37.6%). The results of the binary logistics regression analysis showed that relative to the moderate PEF% group, the risk of postoperative pneumonia was significantly increased in the marginal PEF% [odds ratio (OR) 2.076; 95% confidence interval (CI): 1.211-3.558; P=0.008] and excellent PEF% (OR 1.962; 95% CI: 1.129-3.411; P=0.017) groups. Relative to the good FVC% group, the risk of postoperative pneumonia was significantly increased in the marginal FVC% (OR 2.125; 95% CI: 1.226-3.683; P=0.007) and moderate FVC% (OR 2.230; 95% CI: 1.298-3.832; P=0.004) groups. The OS analysis did not reveal any correlations among the pulmonary function parameters and OS in this cohort. CONCLUSIONS: Preoperative PEF% and FVC% are associated with postoperative pneumonia in NSCLC patients undergoing VATS lobectomy. Preoperative PEF% is as important as FVC% in pulmonary function assessment before lung surgery.

Bioinformatics analysis of differentially expressed genes in tumor and paracancerous tissues of patients with lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is the main pathological type of non-small cell lung cancer (NSCLC). In this study, we analyzed the gene expression profile of lung adenocarcinoma tumor and paracancerous tissues by bioinformatics to assess the genes and signal pathways related to lung adenocarcinoma. METHODS: The expression data of GSE7670, GSE27262, and GSE32863 were downloaded from the Gene Expression Omnibus (GEO) database. The three microarray data sets were integrated to obtain common differential expression genes of lung adenocarcinoma tumor and adjacent tissues. The STRING database was used to construct the protein-protein interaction (PPI) network of lung adenocarcinoma and mine the gene modules and core genes in the network, and the online tools, GEPIA and Kaplan-Meier plotter were used to further verify and analyze the core genes. RESULTS: There were 109 pairs of lung adenocarcinoma tissues and matched paracancerous normal lung tissues in the three data sets. Eighty-three differentially expressed genes were identified, including 16 up-regulated and 67 down-regulated genes, and 60 differentially expressed genes were successfully incorporated into the PPI network complex. Eleven core genes were identified in the PPI network complex, including three up-regulated (COMP, SPP1, COL1A1) and eight down-regulated genes (CDH5, CAV1, CLDN5, LYVE1, IL6, VWF, TEK, PECAM1). These core genes were verified by the GEPIA tumor database. Survival analysis showed that expression of the core genes was significantly related to the prognosis of lung adenocarcinoma. KEGG pathway analysis of core genes showed six genes (COMP, SPP1, COL1A1, IL6, VWF, TEK) were significantly enriched in the PI3K-Akt signaling-pathway (P=1.62E-06). CONCLUSIONS: By analyzing the differential expression genes of lung adenocarcinoma and paracancerous normal tissues with bioinformatics, 11 genes with significant differential expression and significant influence on prognosis were identified. The findings may provide new concepts for developing diagnosis and treatment targets and prognosis markers for lung adenocarcinoma.

Trends in cancer incidence and mortality rates in the United States from 1975 to 2016.

BACKGROUND: Cancer is the second leading cause of death in the United States (US). The goal of this study was to characterize the trends in cancer incidence and mortality in the US from 1975 to 2016. METHODS: In this study, we analyzed 4,711,958 cancer cases and 21,489,462 cancer death cases from the Surveillance, Epidemiology and End Results (SEER) database. Cancer incidence and mortality were assessed according to sex, race, and age group. Cancer survival rates between 2010 and 2016 were also examined. RESULTS: The continuous decline in the overall cancer mortality rate from the early 1990s has resulted in overall decreases of 33.6% and 23.6% in the cancer mortality rates of males and females, respectively. In males, the top three leading cancers and causes of cancer death from 1975 to 2016 were prostate, lung and bronchial, and colon and rectal cancers, while in females, the top three leading cancers and causes of cancer death from 1979 to 2016 were breast, lung and bronchial, and colon and rectal cancers. The 5-year relative survival rates of males and females for all cancers combined, diagnosed from 2010-2016, were 68.5% and 70.1%, respectively. The overall cancer incidence and mortality were higher in males than females from 1975-2016. Also, black people had higher mortality and shorter survival rates for all cancers combined compared with white people (in both sexes). CONCLUSIONS: This study presents a comprehensive overview of cancer incidence and mortality in the US over the past 42 years. Such information can provide a scientific basis for cancer prevention and control.

Excessive intravenous crystalloid infusion after video-assisted thoracoscopic surgery lobectomy is associated with postoperative pneumonia.

BACKGROUND: Video-assisted thoracoscopic surgery has been widely used in thoracic surgery worldwide. Our goal was to identify the risk factors for postoperative pneumonia in patients undergoing video-assisted thoracoscopic surgery lobectomy. METHODS: A retrospective analysis of adult patients undergoing video-assisted thoracoscopic surgery lobectomy between 2016 and 05 and 2017-04 was performed. We used univariate analyses and multivariate analyses to examine risk factors for postoperative pneumonia after lobectomy. RESULTS: The incidence of postoperative pneumonia was 19.7% (n = 143/727). Patients with postoperative pneumonia had a higher postoperative length of stay and total hospital care costs when compared to those without postoperative pneumonia. Multivariate analysis showed that body mass index grading ≥24.0 kg/m2 (vs. <24.0 kg/m2: odds ratio 1.904, 95% confidence interval 1.294-2.802, P = 0.001) and right lung lobe surgery (vs. left lung lobe surgery: odds ratio 1.836, 95% confidence interval 1.216-2.771, P = 0.004) were independent risk factors of postoperative pneumonia. Total intravenous crystalloid infusion grading in the postoperative 24 h ≥ 1500 mL was also identified as the risk factors (vs. 1000 to < 1500 mL: odds ratio 2.060, 95% confidence interval 1.302-3.260, P = 0.002). CONCLUSIONS: Major risk factors for postoperative pneumonia following video-assisted thoracoscopic surgery lobectomy are body mass index grading ≥24.0 kg/m2, right lung lobe surgery and total intravenous crystalloid infusion grading in the postoperative 24 h ≥ 1500 mL.

The Predictive Value of Tumor Mutation Burden on Efficacy of Immune Checkpoint Inhibitors in Cancers: A Systematic Review and Meta-Analysis.

Background: Despite an increasing understanding about tumor mutation burden (TMB) in cancer immunity and cancer immunotherapy, the comprehensive cognition between TMB and efficiency of immune checkpoint inhibitors (ICIs) is still lacking. A systematic review and meta-analysis was conducted to evaluate the predictive value of TMB on efficacy of ICIs. Methods: Systematic literature search was conducted on PubMed, EMBASE, Web of Science and Cochrane Library up to June 16, 2019. Pooled odds ratio (OR) of objective response rate (ORR), hazard ratio (HR) of progression-free survival (PFS) and overall survival (OS) were estimated by inverse variance weighted fixed-effects model (I 2 ≤ 50%) or DerSimonian-Laird random-effects model (I 2 > 50%). In addition, heterogeneity analysis, sensitivity analysis, publication bias and subgroup analysis were conducted. Moreover, fractional polynomial regression was conducted to investigate the dose-response relationship between TMB cutoffs and efficacy of ICIs. Furthermore, we assessed ORR by TMB and programmed cell death ligand 1 (PD-L1) expression after layering each other in studies which the two could be both acquired. Results: Three thousand six hundred fifty-seven records were retrieved through database searching, and 29 studies with 4,431 patients were finally included in the meta-analysis. TMB high group had significantly improved ORR (pooled OR 3.31, 95% CI 2.61, 4.19, P < 0.001), PFS (pooled HR 0.59, 95% CI 0.49, 0.71, P < 0.001) and OS (pooled HR 0.68, 95% CI 0.53, 0.89, P = 0.004). Sensitivity analyses illustrated the results were stable, and publication bias was identified in ORR. Subgroup analyses showed the predictive value of TMB was significant in non-small-cell lung cancer (except for the OS) and melanoma. In addition, heterogeneity was substantial in targeted next generation sequencing group but tiny in whole exome sequencing group. Furthermore, TMB and PD-L1 expression were capable to predict improved ORR of ICIs after stratification of each other, with tiny heterogeneity. Conclusions: High tumor mutation burden predicted improved efficacy of immune checkpoint inhibitors in cancers, and targeted next generation sequencing for estimating tumor mutation burden in clinic should be standardized to eliminate heterogeneity in the future. Moreover, tumor mutation burden and programmed cell death ligand 1 expression were independent factors on predicting efficacy of immune checkpoint inhibitors.

miR-517a is up-regulated in glioma and promotes glioma tumorigenesis in vitro and in vivo.

miR-517a has been reported to act as an oncogenic miRNA in human hepatocellular carcinoma and lung cancer. However, the roles and underlying molecular mechanism of miR-517a in glioma remain unclear. In the present study, the expression of miR-517a in clinical glioma tissues and glioma cell lines was examined by quantitative real-time PCR (qRT-PCR). Transfected with knockdown or forced expression of miR-517a, the effects of miR-517a on cell proliferation, migration, and invasion were detected through in vitro and in vivo tumorigenesis assays. Here, we report that miR-517a expression was up-regulated in glioma tissues when compared with normal brain tissues, and up-regulation of miR-517a level is tightly correlated with the status of pathology classification of glioma. A functional assay found that overexpression of miR-517a in glioma cells markedly promoted or suppressed cell proliferation, colony formation, migration and invasion, respectively. Moreover, we revealed that the knockdown of miR-517a dramatically suppressed glioma cell growth, migration, and invasion in vitro and in vivo Furthermore, we found that knockdown of miR-517a significantly induced apoptosis. Therefore, miR-517a acts an oncogenic miRNA that promotes tumor progression in glioma, and thus may become a promising therapeutic candidate for glioma.

Risk factors of postoperative pulmonary complications after minimally invasive anatomic resection for lung cancer.

PURPOSE: This study investigated the perioperative risk factors of postoperative pulmonary complications (PPCs) after minimally invasive anatomic resection for lung cancer. PATIENTS AND METHODS: We retrospectively reviewed the data from medical records of 729 lung cancer patients undergoing minimally invasive anatomic lung resections between January 2017 and December 2017. Univariate and binary logistic regression analyses were performed to select the independent risk factors for PPCs during the patient's postoperative hospitalization after surgery. RESULTS: The incidence of PPCs was 24.8% (n=181/729). No patient died during the period of hospitalization. Logistic regression analysis revealed that body mass index (BMI) ≥24.0 kg/m2 (vs <24.0 kg/m2: OR 1.514, 95% CI 1.057-2.167, P=0.024), single segmentectomy (vs single lobectomy: OR 2.115, 95% CI 1.150-3.891, P=0.016), bilobectomy or combined lobectomy and segmentectomy (vs single lobectomy: OR 2.731, 95% CI 1.013-7.361, P=0.047), and right lung lobe surgery (vs left lung lobe surgery: OR 1.519, 95% CI 1.046-2.205, P=0.028) were independent risk factors for PPCs in lung cancer patients who received minimally invasive anatomic lung resections. CONCLUSION: Individual factors such as BMI ≥24.0 kg/m2, single segmentectomy, bilobectomy or combined lobectomy and segmentectomy, and right lung lobe surgery were independent risk factors of PPCs, which should be helpful for risk stratification, patient counseling, and perioperative care for lung cancer patients.

KCTD11 inhibits growth and metastasis of hepatocellular carcinoma through activating Hippo signaling.

A lack of effective prognostic biomarkers and molecular targets is a serious problem in hepatocellular carcinoma. KCTD11, reported as a tumor suppressor, are still not well understood. In this study, KCTD11 was found low-expressed in HCC tissues and cell lines. The HCC patients with low expression of KCTD11 suggested shorter overall survival. We found KCTD11 inhibiting cell proliferation in vitro and tumor growth in vivo, by activating p21 and repressing cycle related proteins. KCTD11 also inhibited cell adhesion by decreasing CTGF and CLDN1. We found CTGF binding COL3A1 in HCCLM3, which might lead to reduction of COL3A1 expression. KCTD11 also inhibited cell migration and invasion in HCC, by repressing MMPs and EMT. We found the tumor suppression function of KCTD11 was at least partly through activating Hippo pathway in HCC. Base on the enhanced Hippo pathway, KCTD11 could activate p21 by stabilizing p53 or promoting the MST1/ GSK3ß/p21 signaling in HCC. Overall, these results suggest that KCTD11 works as a tumor suppressor and owns prognostic and therapeutic potentials in HCC.

Initial experience of Da Vinci robotic thoracic surgery at the First Affiliated Hospital of Zhejiang University.

Robot-assisted thoracic surgery (RATS) is a relatively new but rapidly adopted technique, pioneered by the urological and gynecological departments. The primary objective of this study is to present the current status, a series of improvement and innovation of Da Vinci robotic surgery in the Department of Thoracic Surgery at First Affiliated Hospital of Zhejiang University. In addition, we discuss the prospect of robotic surgical technology.