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Hepatocellular carcinoma (HCC) is closely associated with chronic liver disease and possesses a high incidence. DEP domain containing 1B (DEPDC1B) expression has been found to be upregulated in HCC according to bioinformatics analysis. This paper sought to study the specific role of DEPDC1B in HCC. The data of DEPDC1B expression and individual overall survival in HCC and normal liver tissues were acquired from UALCAN database. The association between DEPDC1B and the downstream signal, kinesin family member 23 (KIF23), was determined using LinkedOmics and STRING database, and subsequently confirmed by co-immunoprecipitation assay. The expression levels of DEPDC1B and KIF23 in normal hepatic epithelial cells and HCC cell lines were assessed by RT-qPCR and Western blotting, respectively. Following transfection with small interference RNA-DEPDC1B, the influences of DEPDC1B knockdown on cell proliferation, colony formation, cell cycle, cell invasion, migration, and KIF23 expression were evaluated. In addition, the effects of KIF23 overexpression on the above aspects of HCC cells were also determined, as well as the expression level of p53 signaling-related proteins. The results indicated that DEPDC1B was highly expressed in HCC cells. DEPDC1B knockdown inhibited the proliferation, migration, invasion, cycle, and KIF23 expression in HCC cells. Moreover, KIF23 overexpression reversed the inhibitory effect of DEPDC1B knockdown in HCC cells and the activation of the p53 signaling. In conclusion, DEPDC1B knockdown exerts anti-cancer role in HCC by activating the p53 signaling through KIF23.

Objectives Understanding if police malfeasance might be “contagious” is vital to identifying efficacious paths to police reform. Accordingly, we investigate whether an officer’s propensity to engage in misconduct is associated with her direct, routine interaction with colleagues who have themselves engaged in misbehavior in the past. Methods Recognizing the importance of analyzing the actual social networks spanning a police force, we use data on collaborative responses to 1,165,136 “911” calls for service by 3475 Dallas Police Department (DPD) officers across 2013 and 2014 to construct daily networks of front-line interaction. And we relate these cooperative networks to reported and formally sanctioned misconduct on the part of the DPD officers during the same time period using repeated-events survival models. Results Estimates indicate that the risk of a DPD officer engaging in misconduct is not associated with the disciplined misbehavior of her ad hoc, on-the-scene partners. Rather, a greater risk of misconduct is associated with past misbehavior, officer-specific proneness, the neighborhood context of patrol, and, in some cases, officer race, while departmental tenure is a mitigating factor. Conclusions Our observational findings—based on data from one large police department in the United States—ultimately suggest that actor-based and ecological explanations of police deviance should not be summarily dismissed in favor of accounts emphasizing negative socialization, where our study design also raises the possibility that results are partly driven by unobserved trait-based variation in the situations that officers find themselves in. All in all, interventions focused on individual officers, including the termination of deviant police, may be fruitful for curtailing police misconduct—where early interventions focused on new offenders may be key to avoiding the escalation of deviance.

Previous studies have confirmed that microRNA (miR)-128-3p is expressed at low levels in gastric cancer (GC), and low miR-128-3p expression promotes the growth of GC cells. However, whether the dysregulation of miR-128-3p expression affects tumor-infiltrating lymphocytes (TILs) and leads to immune escape remains unclear. In the present study, predictive bioinformatics approaches showed that miR-128-3p expression was inversely correlated with tumor-infiltrating lymphocyte enrichment. When CD4 + T cells and regulatory T cells (Tregs) were enriched, lower miR-128-3p expression was associated with worse overall survival. However, when numbers of CD8 + T cells were decreased, the upregulation of miR-128-3p expression had a favorable effect on GC prognosis. Dual-luciferase reporter assays and cell biology experiments revealed that interleukin 16 (IL16) was the target of miR-128-3p and was negatively regulated by miR-128-3p. In addition, GC cells were cocultured with T lymphocytes, and the subsequent flow cytometric analysis showed that overexpression of miR-128-3p in tumor cells decreased the percentages of CD4+ CD25+ Foxp3+ Tregs by downregulating IL16 expression in GC, whereas miR-128-3p inhibition had the opposite effect. Moreover, the recombinant IL16 reversed the effects of miR-128-3p overexpression, and a competitive antibody against the IL16 receptor CD4 also reversed the effects of miR-128-3p knockdown. These studies identified the mechanism by which the miR-128-3p/IL16 axis promotes the infiltration of CD4+ Tregs in GC, and this mechanism will be a promising therapeutic target in GC immunotherapy.

Background: Tumor mutational burden (TMB) is a potential biomarker to predict tumor response to immuno-oncology agents in patients with metastatic non-small cell lung cancer (NSCLC). Materials and Methods: A multi-site cohort study evaluated patients diagnosed with stage IV NSCLC between 2012 and 2019 who had received comprehensive genomic profiling (CGP) and any NSCLC-related treatment at 9 U.S. cancer centers. Baseline characteristics and clinical outcomes were compared between patients with TMB 10 showed a significant association towards longer overall survival (OS) (HR: 0.43, 95% CI: 0.21–0.88, p = 0.02) and progression-free survival (PFS) (HR: 0.43, 95% CI: 0.21–0.85, p = 0.02) in patients treated with first-line immunotherapy and tested by Foundation Medicine or Caris at treatment initiation. Conclusions: TMB levels greater than or equal to 10 mut/Mb, when tested by Foundation Medicine or Caris at treatment initiation, were significantly associated with improved OS and PFS among patients treated with first-line immunotherapy-containing regimens. Additional prospective research is warranted to validate this biomarker along with PD-L1 expression.

Pyroptosis is an inflammatory programmed cell death, showing potentials to be a novel anti-cancer approach. However, the roles of pyroptosis-related (PR) genes (PRGs) in pancreatic adenocarcinoma (PAAD) remain elusive. In the present study, we constructed a novel PR risk signature through the lasso regression analysis. The risk signature was greatly conducive to PAAD prognostic assessment. PR risk score was identified as an independent prognostic factor and could distinguish the prognostic differences of most clinical subgroups. Meanwhile, it could improve the traditional prognostic models based on TNM-staging. Next, its prognostic value was also tested in five validation cohorts. Using CIBERSORT, ESTIMATE, and ssGSEA algorithms, the effects of PR risk signature on tumor immune microenvironment (TIM) were explored. High PR risk suppressed antitumor immune through decreasing the infiltrating levels of CD8 T and NK cells. The genomic information and histological expression of risk PRGs were uncovered by USCA and HPA databases. Somatic mutation, methylation alteration, and homozygous CNV of eight PRGs barely occurred in PAAD samples. As for therapeutic correlation, PR risk score may not predict the efficacy of PD-1/L1 inhibitors and was weakly associated with multiple drug susceptibilities. Finally, the biofunctions of toll like receptor 3 (TLR3) in pancreatic cancer (PC) cells were investigated through qPCR, MTT, colony formation, and Transwell assays. Overexpression of TLR3 could promote the proliferation, migration, and invasion of PC cells. In conclusion, PRGs play crucial roles in prognosis, progression, and immune microenvironment of PAAD. TLR3 is expected to be a promising therapeutic target.

Glioma is one of the leading causes of tumor-related deaths worldwide, but its potential mechanism remains unclear. This study aimed to explore the biological role and potential mechanism of argininosuccinate synthase 1 (ASS1) in glioma. The relative expression levels of ASS1 in glioma specimens and cell lines were calculated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. The biological functions of ASS1 were demonstrated using the 5-ethynyl-2ʹ-deoxyuridine (EdU) assay, transwell assay, and in vivo experiments. In addition, methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), and luciferase reporter assays were performed to explore the molecular mechanism of ASS1 in glioma. ASS1 expression levels were found to be downregulated in glioma specimens and cell lines. Functionally, we confirmed that ASS1 inhibited glioma cell proliferation, migration, invasion, and growth both. Furthermore, we found that ASS1 was a target of N(6)-adenosine-methyltransferase-14 (METTL14)-mediated N6-methyladenosine (m6A) modification. Overexpression of METTL14 markedly elevated ASS1 mRNA m6A modification and suppressed ASS1 mRNA expression. We also revealed that METTL14-mediated ASS1 mRNA degradation relied on the YTH m6A RNA-binding protein 2 (YTHDF2)-dependent pathway. We confirmed that decreased ASS1 expression promoted the cell proliferation, migration, and invasion in glioma, and that the METTL14/ASS1/YTHDF2 regulatory axis may be an effective therapeutic target for glioma.

Most patients with ovarian cancer (OC) get remission after undergoing cytoreductive surgery and platinum-based standard chemotherapy, but more than 50% of patients with advanced OC relapse within the first 5 years after treatment and develop resistance to standard chemotherapy. The production of medicinal properties is the main reason for the poor prognosis and high mortality of OC patients. Cisplatin (DDP) resistance is a major cause for poor prognosis of OC patients. PTPRZ1 can regulate the growth and apoptosis of ovarian cancer cells, while the molecular mechanism remains unknown. This study was designed to investigate the roles of PTPRZ1 in DDP-resistant OC cells and possible mechanism. PTPRZ1 expression in OC tissues and normal tissues was analyzed by GEPIA database and verified by Real-time Quantitative Reverse Transcription PCR (RT-PCR) assay. PTPRZ1 expression in normal ovarian cancer cells and DDP-resistant OC cells was also analyzed. Subsequently, RT-PCR, Western blot, MTT experiment and flow cytometry were used to assess the effects of PTPRZ1-PI3K/AKT/mTOR regulating axis on DDP resistance of OC. PTPRZ1 expression was abnormally low in OC tissues, and notably reduced in DDP-resistant OC cells. MTT experiment and flow cytometer indicated that overexpression of PTPRZ1 enhanced the DDP sensitivity of OC cells and promoted the cell apoptosis. Moreover, the results of our research showed that PTPRZ1 might exert its biological effects through blocking PI3K/AKT/mTOR pathway. PTPRZ1 overexpression inhibitied OC tumor growth and resistance to DDP in vivo. Overall, PTPRZ1 might suppress the DDP resistance of OC and induce the cytotoxicity by blocking PI3K/AKT/mTOR pathway.

It was to explore the clinical efficacy and safety of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) targeted drugs combined with hyaluronic acid-gadolinium sesquioxide-nanoparticles (HA-Gd2O3-NPs) in non-small cell lung cancer (NSCLC). In this study, 70 patients with stage IV EGFR mutant NSCLC diagnosed in the First Affiliated Hospital of Jinzhou Medical University were selected. They were randomly divided into the combined group (35 cases) and the control group (35 cases). HA-Gd2O3-NPs were prepared by hydrothermal polymerization, and combined with EGFR-TKI in the clinical treatment of NSCLC. The results showed that HA-Gd2O3-NPs were spherical with a uniform particle size of about 124 nm. The NSCLC survival rate of the combined group was 37.2 ± 5.3% under 6 Gy X-ray irradiation, and that of the control group was 98.4 ± 12.6% under 6 Gy X-ray irradiation. The total effective rate of the control group (20%) was significantly lower than that of the study group (42.86%) (P

Background: Globally, colorectal cancer (CRC) is one of the most lethal malignant diseases. However, the currently approved therapeutic options for CRC failed to acquire satisfactory treatment efficacy. Tailoring therapeutic strategies for CRC individuals can provide new insights into personalized prediction approaches and thus maximize clinical benefits. Methods: In this study, a multi-step process was used to construct an immune-related genes (IRGs) based signature leveraging the expression profiles and clinical characteristics of CRC from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. An integrated immunogenomic analysis was performed to determine the association between IRGs with prognostic significance and cancer genotypes in the tumor immune microenvironment (TIME). Moreover, we performed a comprehensive in silico therapeutics screening to identify agents with subclass-specific efficacy. Results: The established signature was shown to be a promising biomarker for evaluating clinical outcomes in CRC. The immune risk score as calculated by this classifier was significantly correlated with over-riding malignant phenotypes and immunophenotypes. Further analyses demonstrated that CRCs with low immune risk scores achieved better therapeutic benefits from immunotherapy, while AZD4547, Cytochalasin B and S-crizotinib might have potential therapeutic implications in the immune risk score-high CRCs. Conclusions: Overall, this IRGs-based signature not only afforded a useful tool for determining the prognosis and evaluating the TIME features of CRCs, but also shed new light on tailoring CRCs with precise treatment.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. HCC cells possess biological characteristics of high invasion and metastasis. In this respect, to prevent cancer cell invasion and metastasis and early active intervention, we herein screened through the TCGA database for further prognostic analysis including overall survival and disease-free survival . The Kaplan-Meier curve suggested that Cyclin-Dependent Kinase 4 (CDK4) might be an independent prognostic factor for HCC. Moreover, we performed mRNA expression analysis to measure CDK4 levels in normal liver tissues and HCC tissues, and immunohistochemistry analysis to detect protein level of CDK4 in Non-tumor tissue and HCC tissues . Our findings indicated that the expression of CDK4 was significantly higher in tumor tissues compared with Non-tumor tissue in HCC, which increased from HCC stage 1 to 3. Furthermore, the results of transwell-assay indicated that knocking down CDK4 significantly suppresses the invasion and migration of HCC cells, and the results of bioinformatics analysis revealed that genes closely associated with CDK4 are potentially worthy of further investigation. Additionally, the results of Western Blot indicated CDK4 regulates epithelial mesenchymal transition in HCC,and CDK4 appears to regulate EMT and HCC progression via the Wnt/β-catenin pathway. Collectively, this study found the key target gene through bioinformatic analysis and further functional validation through cell experiments. In particular, CDK4 is anticipated to become a crucial hub gene to snipe the metastasis of cancer cells in HCC. Abbreviations: Hepatocellular carcinoma (HCC);Cyclin-Dependent Kinase 4(CDK4);Genomic Data Commons (GDC); genes; EC, Endometrial cancer; GEO, gene expression omnibus; GO, Gene Ontology; GSEA, Gene set enrichment analysis; KEGG, Database; TCGA, The Cancer Genome Atlas; TSGs, tumor suppressor genes;epithelial mesenchymal transition (EMT).

Breast cancer (BC), an extremely aggressive malignant tumor, causes a large number of deaths worldwide. In this study, we pooled profile datasets from three cohorts to illuminate the underlying key genes and pathways of BC. Expression profiles GSE42568, GSE45827, and GSE124646, including 244 BC tissues and 28 normal breast tissues, were integrated and analyzed. Differentially expressed genes (DEGs) were screened out based on these three datasets. Functional analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway were performed using The Database for Annotation, Visualization and Integrated Discovery (DAVID). Moreover, Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING) and Molecular Complex Detection (MCODE) plugin were utilized to visualize protein protein interaction (PPI) of these DEGs. The module with the highest connectivity of gene interactions was selected for further analysis. All of these hub genes had a significantly worse prognosis in BC by survival analysis. Additionally, four genes (CDK1, CDC20, AURKA, and MCM4) dramatically were enriched in oocyte meiosis and cell cycle pathways through re-analysis of DAVID. Moreover, the mRNA and protein levels of CDK1, CDC20, AURKA, and MCM4 were significantly increased in BC patients. In addition, knockdown of CDK1 and CDC20 by small interfering RNA remarkably suppressed cell migration and invasion in MCF-7 and MDA-MB-231 cells. In conclusion, our results suggested that CDK1, CDC20, AURKA, and MCM4 were reliable biomarkers of BC via bioinformatics analysis and experimental validation and may act as prospective targets for BC diagnosis and treatment.

AKT Serine/Threonine Kinase 3 (AKT3) has been reported to play an important role in different tumors. However, its clinical value, biological function, and molecular mechanism in testicular germ cell tumors (TGCT) remains unclear. In the current study, we applied the Gene Set Cancer Analysis (GSCA), UCSC XENA, Gene Expression Omnibus (GEO), the Human Protein Atlas (HPA), LinkedOmics, DiseaseMeth version 2.0, TISIDB, and other databases for TGCT data mining. Then, we investigated AKT3’s mechanism of action and clinical survival significance via bioinformatics followed by in vitro experiments. We found that AKT3 was upregulated and had frequent copy number amplifications in TGCT, which were associated with poor survival outcomes of patients. On the other hand, mutations that led to AKT3 loss-of-function were correlated to a better prognosis in patients. Moreover, AKT3 silencing significantly inhibited the proliferation, DNA synthesis and colony formation of NCCIT cells (a TGCT cell line). AKT3 might participate in TGCT progression through multiple signaling pathways, such as ErbB, oxidative phosphorylation, and affecting tumor immune infiltration. Also, the upregulation of AKT3 mRNA expression might be driven by the hypomethylation of its promoter region. Overall, AKT3 is a potential TGCT oncogene and can be further used as a therapeutic target.

This study aims to investigate the potential clinical function of long non-coding RNA CERS6-AS1 (lncRNA CERS6-AS1) integrated miR-567 in gastric cancer. The expression of CERS6-AS1 in gastric cancer tissues was detected through RT-qPCR in contrast to the normal tissues. The correlation between the expression of lncRNA CERS6-AS1 and the characteristics of clinical data was analyzed. Kaplan-Meier curve was used to assess the survival analysis, while Cox proportional hazards model multivariate analysis was performed to evaluate the prognostic risk factors of gastric cancer to verify the prognostic possibility of CERS6-AS1. The expression of CERS6-AS1 in different gastric cancer cells was detected, being the development of gastric cancer cells after knockdown CERS6-AS1 studied using CCK-8, Transwell migration, and invasion detection methods. The targeting effect and interaction between CERS6-AS1 and miR-567 through biological analysis and luciferase activity detection. The expression of lncRNA CERS6-AS1 was elevated in gastric cancer tissues and cells. The results of this study demonstrate that the condition of gastric cancer patients was related to the expression of CERS6-AS1, and therefore CERS6-AS1 might be a prognostic factor for the progression of gastric cancer. In addition, the ability of gastric cancer cells to proliferate, migrate and invade could be reduced by knockdown CERS6-AS1. After CERS6-AS1 knockdown, the expression level of miR-567 in gastric cancer tissues decreased, while the expression level of miR-567 increased. In conclusion, lncRNA CERS6-AS1 might promote the progression of gastric cancer and had the potential as a prognostic marker of gastric cancer.

Circadian dysregulation involves malignant tumor initiation and progression, but the understanding of circadian rhythm's roles in bladder cancer (BCa) remains insufficient. The circadian rhythm-related genes were collected and clustered based on the Cancer Genome Atlas (TCGA), and the clustering was significantly associated with the prognosis and risk clinicopathological features. Through genomic difference analysis and gene pairing, a circadian rhythm-related signature was successfully established. Kaplan-Meier survival analysis and time-dependent receiver operating curves displayed that the prognosis model was a reliable prognosis biomarker both in the training cohort (n = 396, P = 2.687e-10) and external validation cohort (n = 224, P = 1.45e-02). The patients with high risk have high immune infiltration and high expression of immune checkpoint genes, which partly account for the poor prognosis. TIDE algorithm and the validation in IMvigor210 cohort indicated that the risk signature was a promising marker for the immunotherapeutic response. The risk model could also predict the therapeutic response of cisplatin, which was validated in the Genomics of Drug Sensitivity in Cancer database (P = 0.0049), TCGA (P = 0.038), and T24 BCa cells treated with cisplatin. The functional enrichment showed the risk model was significantly correlated with some malignant phenotypes, such as angiogenesis, epithelial-mesenchymal transition, and KRAS signaling pathway. Totally, we proposed a novel circadian rhythm-related signature for prognosis evaluation, which also helped to predict the immune infiltration and cisplatin sensitivity in BCa.

Intratumoral immune cells were reported to be associated with prognosis of bladder urothelial carcinoma (BUC). However, the role of immune cells related genes in BUC prognosis is less well defined. In the study, we analyzed data retrieved from the Cancer Genome Atlas database and found higher neutrophils and lower T cells infiltration in BUC tumor tissues were significantly correlated with patients' worse prognosis. Additionally, the expression levels of 164 genes were significantly correlated with T cells and neutrophils proportions. A Cox proportional-hazards model integrating 6 genes expression (EMP1, RASGRP4, HSPA1L, AHNAK, SLC1A6, and PRSS8) was identified. The 6-gene signature outperformed other clinical factors in risk prediction and was an independent prognostic factor for BUC. The findings were further conformed in three Gene Expression Omnibus datasets (n=331) and Jiangsu Province Hospital cohort (n = 46). Gene set enrichment analysis revealed that the model was highly involved in some immune-related pathways. A comprehensive nomogram combining the model and other clinical parameters was finally constructed to facilitate clinical application. In conclusion, a T cell and neutrophil-associated 6-gene prognostic model was identified for the survival prediction of BUC patients.

The phosphoprotein phosphatase catalytic subunit (PPPCs) family has been shown to play an important role in the development and progression of various malignancies, but its expression patterns and biological functions in breast cancer (BC) remain unclear. Therefore, we aimed to investigate the clinical significance and biological functions of the PPPCs family to understand its possible significance in the diagnosis, prognosis and treatment of breast cancer. We comprehensively investigated the expression levels, diagnostic accuracy, prognostic outcomes, biological functions and effects on immune cell infiltration of the PPPCs family in breast cancer using online databases. Except for PPP1CB, PPP1CC, PPP5C and PPEF1, the mRNA expression levels of the PPPCs family in breast cancer tissues were significantly different from those in paracancerous tissues. The differentially expressed genes (DEGs) were associated with the clinicopathological parameters and prognosis of breast cancer. The DEGs were mainly associated with the WNT signaling pathway, antigen presentation and DNA repair. In addition, the DEGs significantly affected the infiltration of immune cells in breast cancer tissues. Among the PPPCs family, PPP1CA and PPP4C played a prominent role in the progression of breast cancer, and inhibition of PPP1CA and PPP4C expression by siRNA can significantly inhibit breast cancer cells proliferation and migration. In conclusion, the PPPCs family, especially PPP1CA and PPP4C, could be used as new biomarkers to improve diagnostic accuracy, predict prognosis and novel targets for the treatment of breast cancer.

Long non-coding RNAs (LncRNAs) have crucial function in epithelial–mesenchymal transition (EMT) in pancreatic cancer. It is necessary to comprehensively analyze the potential role of EMT-related lncRNA in pancreatic cancer. In the present study, genomic data of pancreatic cancer from the TCGA database were downloaded and we found 368 EMT-related lncRNAs. According to the expression characteristics of prognostic-related lncRNAs, all samples could be divided into two clusters with different clinical outcomes and different tumor microenvironments. Moreover, an eleven EMT-related lncRNAs signature was established and verified. Patients with pancreatic cancer in the high-risk group had a shorter overall survival than those in the low-risk group and the signature could act as an independent prognostic factor. Further analysis suggested that the EMT-related lncRNAs might affect the prognosis of patients through immune mechanisms. All findings indicated that the signature and eleven lncRNAs might serve as potential prognostic biomarkers and therapeutic targets in the treatment of pancreatic cancer.