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.

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.

Downregulation of HDAC6 promotes angiogenesis in hepatocellular carcinoma cells and predicts poor prognosis in liver transplantation patients.

HDAC6, a member of histone deacetylation family, is reported to play critical roles in transcription regulation, cell cycle progression, and cancer development. However, the expression status and significance of HDAC6 in hepatocellular carcinoma (HCC) is still controversial, and little is known about the role of HDAC6 in HCC angiogenesis and the correlation between expression of HDAC6 and prognosis of HCC patients with liver transplantation (LT). Our experiments showed HDAC6 was significantly downregulated in HCC tissues (P = 0.025), and low expression of HDAC6 was found to be closely associated with recurrence (P = 0.006), and could predict poor recurrence-free survival (P = 0.047) for HCC patients with LT. Moreover, knockdown of HDAC6 could promote HUVEC migration, proliferation, and tube formation in vitro, and suppress HCC cell apoptosis, and promote HCC cell proliferation in hypoxia. Remarkably, knockdown of HDAC6 could significantly up-regulate the expression of HIF-1α and VEGFA in vivo and in vitro, which facilitated HIF-1α mediated angiogenesis in HCC. Further study showed that HDAC6 was down-regulated under hypoxia in a time dependent manner. Hence, the present findings suggested a role for suppression of HDAC6 in promoting the angiogenesis in HCC by HIF-1α/VEGFA axis. HDAC6 may serve as a recurrence predictive factor for HCC after LT and pharmacological or genetic activation of HDAC6 could be a novel anti-angiogenesis approach for HCC therapy.

Expression and Critical Role of Interleukin Enhancer Binding Factor 2 in Hepatocellular Carcinoma.

Interleukin enhancer binding factor 2 (ILF2), a transcription factor, regulates cell growth by inhibiting the stabilization of mRNA. Currently, its role has gained recognition as a factor in the tumorigenic process. However, until now, little has been known about the detailed role ILF2 plays in hepatocellular carcinoma (HCC). In this study, we investigated the expression levels of ILF2 in HCC tissue with Western blot and immunohistochemical assays. To examine the effect of ILF2 on liver cancer cell growth and apoptosis, small interfering RNAs (siRNAs) targeting ILF2 were recombined to create lentiviral overexpression vectors. Our results showed higher expression levels of ILF2 mRNA and ILF2 protein in HCC tissue compared with matched peritumoral tissue. Expression of ILF2 may regulate cell growth and apoptosis in liver cancer cells via regulation of B-cell lymphoma 2 (Bcl-2), Bcl-2 related ovarian killer (Bok), Bcl-2-associated X protein (BAX), and cellular inhibitor of apoptosis 1 (cIAP1). Moreover, we inoculated nude mice with liver cancer cells to investigate the effect of ILF2 on tumorigenesis in vivo. As expected, a rapid growth was observed in cancer cells inoculated with a lentiviral vector coding Flag-ILF2 (Lenti-ILF2) compared with the control cells. Hence, these results promote a better understanding of ILF2's potential role as a therapeutic target in HCC.

BAG3 regulates epithelial-mesenchymal transition and angiogenesis in human hepatocellular carcinoma.

Bcl2-associated athanogene 3 (BAG3) protein is a co-chaperone of heat-shock protein (Hsp) 70 and may regulate major physiological and pathophysiological processes. However, few reports have examined the role of BAG3 in human hepatocellular carcinoma (HCC). In this study, we show that BAG3 regulates epithelial-mesenchymal transition (EMT) and angiogenesis in HCC. BAG3 was overexpressed in HCC tissues and cell lines. BAG3 knockdown resulted in reduction in migration and invasion of HCC cells, which was linked to reversion of EMT by increasing E-cadherin expression and decreasing N-cadherin, vimentin and slug expression, as well as suppressing matrix metalloproteinase 2 (MMP-2) expression. In a xenograft tumorigenicity model, BAG3 knockdown effectively inhibited tumor growth and metastasis through reduction in CD34 and VEGF expression and reversal of the EMT pathway. In conclusion, BAG3 is associated with the invasiveness and angiogenesis in HCC, and the BAG3 gene may be a novel therapeutic approach against HCC.

Up-regulation of eEF1A2 promotes proliferation and inhibits apoptosis in prostate cancer.

BACKGROUND: eEF1A2 is a protein translation factor involved in protein synthesis, which possesses important function roles in cancer development. This study aims at investigating the expression pattern of eEF1A2 in prostate cancer and its potential role in prostate cancer development. METHODS: We examined the expression level of eEF1A2 in 30 pairs of prostate cancer tissues by using RT-PCR and immunohistochemical staining (IHC). Then we applied siRNA specifically targeting eEF1A2 to down-regulate its expression in DU-145 and PC-3 cells. Flow cytometer was used to explore apoptosis and Western-blot was used to detect the pathway proteins of apoptosis. RESULTS: Our results showed that the expression level of eEF1A2 in prostate cancer tissues was significantly higher compared to their corresponding normal tissues. Reduction of eEF1A2 expression in DU-145 and PC-3 cells led to a dramatic inhibition of proliferation accompanied with enhanced apoptosis rate. Western blot revealed that apoptosis pathway proteins (caspase3, BAD, BAX, PUMA) were significantly up-regulated after suppression of eEF1A2. More importantly, the levels of eEF1A2 and caspase3 were inversely correlated in prostate cancer tissues. CONCLUSION: Our data suggests that eEF1A2 plays an important role in prostate cancer development, especially in inhibiting apoptosis. So eEF1A2 might serve as a potential therapeutic target in prostate cancer.

MiR-126-3p suppresses tumor metastasis and angiogenesis of hepatocellular carcinoma by targeting LRP6 and PIK3R2.

BACKGROUND: The deregulation of microRNAs has been reported to play a pivotal role in hepatocellular carcinoma (HCC). MiR-126-3p has been reported to be associated with poor prognosis in HCC. However the underlying mechanism of miR-126-3p in HCC remains unclear. METHODS: The expression levels of miR-126-3p in HCC tissues and cells were detected by RT-PCR. Transwell assay and capillary tube formation assay were applied to assess the metastasis and angiogenesis in vitro. Nude mice subcutaneous tumor model was used to perform in vivo study. Dual- luciferase reporter assay was conducted to confirm the direct binding of miR-126-3p and target genes. The changes of biomarker protein levels were examined by western blot and Immunohistochemistry. RESULTS: We observed that the miR-126-3p expression levels in HCC tissues and cells were significantly down-regulated. Through gain- and loss- of function studies, we showed that miR-126-3p dramatically inhibited HCC cells from migrating and invading extracellular matrix gel and suppressed capillary tube formation of endothelial cells in vitro. Furthermore, overexpression of miR-126-3p significantly reduced the volume of tumor and microvessel density in vivo. LRP6 and PIK3R2 were identified as targets of miR-126-3p. Silencing LRP6 and PIK3R2 had similar effects of miR-126-3p restoration on metastasis and angiogenesis individually in HCC cells. Furthermore, the miR-126-3p level was inversely correlated with LRP6 and PIK3R2 in HCC tissues. In addition, the rescue experiments indicated that the metastasis and angiogenesis functions of miR-126-3p were mediated by LRP6 and PIK3R2. CONCLUSION: Our results demonstrates that deregulation of miR-126-3p contributes to metastasis and angiogenesis in HCC. The restoration of miR-126-3p expression may be a promising strategy for HCC therapy.

Long non-coding RNA HOTAIR promotes cell migration and invasion via down-regulation of RNA binding motif protein 38 in hepatocellular carcinoma cells.

Long non-coding RNA HOTAIR exerts regulatory functions in various biological processes in cancer cells, such as proliferation, apoptosis, mobility, and invasion. We previously found that HOX transcript antisense RNA (HOTAIR) is a negative prognostic factor and exhibits oncogenic activity in hepatocellular carcinoma (HCC). In this study, we aimed to investigate the role and molecular mechanism of HOTAIR in promoting HCC cell migration and invasion. Firstly, we profiled its gene expression pattern by microarray analysis of HOTAIR loss in Bel-7402 HCC cell line. The results showed that 129 genes were significantly down-regulated, while 167 genes were significantly up-regulated (fold change >2, p < 0.05). Bioinformatics analysis indicated that RNA binding proteins were involved in this biological process. HOTAIR suppression using RNAi strategy with HepG2 and Bel-7402 cells increased the mRNA and protein expression levels of RNA binding motif protein 38 (RBM38). Moreover, the expression levels of RBM38 in HCC specimens were significantly lower than paired adjacent noncancerous tissues. In addition, knockdown of HOTAIR resulted in a decrease of cell migration and invasion, which could be specifically rescued by down-regulation of RBM38. Taken together, HOTAIR could promote migration and invasion of HCC cells by inhibiting RBM38, which indicated critical roles of HOTAIR and RBM38 in HCC progression.

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.

The up-regulation of histone deacetylase 8 promotes proliferation and inhibits apoptosis in hepatocellular carcinoma.

BACKGROUND: Histone deacetylase 8 (HDAC8), a member of class I HDACs, has been reported to be involved in transcriptional regulation, cell cycle progression, and developmental events, and several studies have shown that HDAC8 plays a critical role in tumorigenesis. However, the expression level and the potential role of HDAC8 in hepatocellular carcinoma (HCC) remain unclear. AIM: The purpose of this study was to investigate protein expression of HDAC8 in HCC tissues and the effects of HDAC8 knockdown on the proliferation and apoptosis of liver cancer cells, and to explore the possible mechanisms. METHODS: First, we used quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemical staining, and western blot to examine the mRNA and protein expression of HDAC8 in HCC cell lines and tissues. Then, we assessed the correlation between clinicopathological parameters and the protein expression of HDAC8. Furthermore, we employed the interfering RNA method to explore the potential role of HDAC8 in HCC progression in vitro. RESULTS: Our results showed that expression of HDAC8 was significantly up-regulated both in HCC cell lines and tumor tissues compared to human normal liver cell line LO2 and corresponding non-tumor tissues. Moreover, we found that HDAC8 knockdown could dramatically inhibit HCC cell proliferation and enhance the apoptosis rate in vitro. Western blot revealed that intrinsic apoptotic pathway proteins, including BAX, BAD, and BAK, were elevated after HDAC8 knockdown. The cleavage of caspase-3 and PARP, which are downstream of intrinsic apoptotic pathway, were also enhanced. In addition, suppression of HDAC8 also elevated the expression of p53 and acetylation of p53 at Lys382, whereas the acetylation of p53 at Lys373 did not change. CONCLUSIONS: Our study revealed that HDAC8 was overexpressed in HCC. HDAC8 knockdown suppresses tumor growth and enhances apoptosis in HCC via elevating the expression of p53 and acetylation of p53 at Lys382. HDAC8 might serve as a potential therapeutic target in HCC.

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.

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.

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.

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.

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.

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.

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.

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.