Dalgaardmassey6675
To study the characteristics of
(
) exonuclease domain mutations in Chinese patients with endometrial carcinoma (EC).
This study analyzed data from 529 patients with EC in The Cancer Genome Atlas (TCGA) and 467 EC patients evaluated at the Shanghai First Maternity and Infant Hospital (SFMIH).
mutation heterogeneity was analyzed in paired curettage and hysterectomy samples from 120 SFMIH patients. Sanger sequencing identified mutations in the
exonuclease domain, and correlations between
mutation status and various clinicopathological features were determined by chi-squared testing and Cohen's kappa analysis, with Kaplan-Meier survival curves generated to assess correlations between
mutation status and overall survival (OS).
Thirty-five mutations were identified in 467 samples (7.5%), and novel mutations were detected in the SFMIH cohort. Compared to the TCGA cohort, the SFMIH cohort had fewer
mutations when matched by age (<60) and histology (endometrioid) (p < 0.001 and p = 0.010, respectively). In our study cohort,
mutations were significantly associated with adjuvant treatment (p = 0.029), and patients with
mutations who underwent chemoradiotherapy had a poor OS (p < 0.0001). Notably, shorter OS was significantly associated with
mutations in hysterectomy samples from patients aged >60 years or with stage I disease in the paired curettage-hysterectomy group.
The significant difference in
mutation profiles between the TCGA and SFMIH cohorts, as well as the poor consistency between the curettage and hysterectomy samples, suggests that different parameters need to be applied to determine the prognosis of patients with EC in China.
The significant difference in POLE mutation profiles between the TCGA and SFMIH cohorts, as well as the poor consistency between the curettage and hysterectomy samples, suggests that different parameters need to be applied to determine the prognosis of patients with EC in China.
The Warburg effect, also known as aerobic glycolysis, plays a dominant role in the development of gastrointestinal (GI) cancers. In this study, we analyzed the expression of key genes involved in the Warburg effect in GI cancers and investigated the effect of suppressing the Warburg effect in vitro in liver cancer cell lines.
The Cancer Genome Atlas (TCGA) RNA-Seq data were used to determine gene expression levels, which were analyzed with GraphPad Prism 7.00. Genetic alterations were queried with cBioPortal. The influence of the Warburg effect on liver cancer cell viability, migration and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity was determined by means of MTT, transwell and GAPDH activity assays.
The levels of expression of genes associated with the Warburg effect were increased in tumors. To our knowledge, this is the first report of upregulated expression of
,
,
,
and
in liver cancer. Clinically, overexpression of these genes was associated with significantly worse overall survival of liver cancer patients. In vitro, selective inhibition of GADPH suppressed the growth and metastasis of Huh-7, Bel7404 and Hep3B hepatocellular carcinoma cell lines.
The Warburg effect may play an important role in GI cancers, especially in liver cancer.
The Warburg effect may play an important role in GI cancers, especially in liver cancer.
The transforming growth factor β regulator 4 (TBRG4) has been proved to be involved in various types of tumor. However, its contribution in human osteosarcoma (OS) is still unclear.
In the present study, immunohistochemistry and quantitative real-time PCR were performed to investigate the expression of TBRG4 in OS tissues obtained from patients and three types of cell lines. The effect of TBRG4 knockdown using lentivirus on tumorigenesis was detected by CCK8, high-content screening analysis, colony formation assay and flow cytometric analysis. Bioinformatics analysis was operated to investigate related signaling pathways following TBRG4 knockdown.
The results showed that the expression of TBRG4 increased significantly in OS tissues and MG63 cell line. #link# TBRG4 knockdown inhibited cell proliferation, colony and tumor formation, while activating cell apoptosis. Ingenuity Pathway Analysis and Western blot assay further indicated that TBRG4 knockdown may regulate the proliferation of human MG63 cells through PI3K/Akt signaling pathway.
Our results suggest that TBRG4 may become a promising therapeutic target for the treatment of human OS.
Our results suggest that TBRG4 may become a promising therapeutic target for the treatment of human OS.
ST7 antisense RNA 1 (ST7-AS1) is a long noncoding RNA that affects the progression of gastric cancer and laryngeal squamous cell carcinoma. Herein, ST7-AS1 expression was detected in cervical cancer tissues and cell lines. In selleck chemicals llc , its biological roles in inducing the aggressive phenotype of cervical cancer and its associated mechanisms of action were illustrated.
ST7-AS1 expression in cervical cancer tissues and cell lines was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Malignancy was determined using Cell Counting Kit-8 assay, flow cytometry, transwell migration and invasion assays, and xenograft experiments. Bioinformatics analysis was performed to predict the interaction between ST7-AS1 and microRNA-543 (miR-543). Luciferase reporter assay, RNA immunoprecipitation assay, Western blotting, qRT-PCR, and rescue experiments were performed to further identify the interactions among ST7-AS1, miR-543, and transient receptor potential melastatin 7 (TRPM7).
ST7-AS1 was upreression, suggesting that this pathway can serve as a promising therapeutic target for cervical cancer.
The newly identified ST7-AS1/miR-543/TRPM7 axis promoted the oncogenicity of cervical cancer cells both in vitro and in vivo. Our study highlighted the importance of this novel axis in cervical cancer progression, suggesting that this pathway can serve as a promising therapeutic target for cervical cancer.
This study was performed to explore the clinical and prognostic significance of APOB mRNA expression, DNA methylation and APOB mutation in patients with low-grade glioma (LGG).
Bioinformatic analysis was conducted using genomic, clinical and survival data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Serum APOB protein levels were measured via immunoturbidimetry in 150 patients with LGG and 100 healthy controls from Hubei General Hospital.
There was a negative association between the levels of APOB mRNA and DNA methylation (r=-0.355, P<0.0001) in patients with LGG from the TCGA database. Additionally, LGG patients with low levels of APOB mRNA exhibited better overall survival (OS) than those with high levels of APOB mRNA (HR=0.637, P=0.0085). The survival time of LGG patients with APOB hypermethylation was markedly longer than that of patients with APOB hypomethylation (HR=0.423, P=0.0185). The prognostic significance of APOB mRNA and DNA methylation was also validated with the CGGA cohort, and a similar conclusion was reached. APOB gene mutations were observed in 3% of patients with LGG from the TCGA database, and no association was detected between APOB mutations and OS (P=0.164). Furthermore, the levels of APOB protein were much lower in patients with LGG than in normal individuals (P=0.0022), and the expression of APOB protein was markedly different among groups when stratified by histological type (P<0.0001) and histological-molecular classification (P<0.0001).
APOB mRNA expression is negatively regulated by DNA methylation in patients with LGG. Low expression or hypermethylation of APOB might predict relatively favorable survival in patients with LGG.
APOB mRNA expression is negatively regulated by DNA methylation in patients with LGG. Low expression or hypermethylation of APOB might predict relatively favorable survival in patients with LGG.Tremendous progress has been achieved in the field of immune checkpoint inhibitors (ICIs) therapy in lung cancer in recent years. To generate robust, long-lasting anti-tumor immune responses in lung cancer patients, combinational ICI therapies have been explored deeply. Conventionally, chemotherapy was considered as immunosuppressive. link2 It is now recognized that chemotherapy could also reinstate cancer cell immune-surveillance and enable the perception of cancer cells as dangerous. That is to say that chemotherapeutic drugs are not only a source of direct cytotoxic effects but also an adjuvant for anti-tumor immunity. Recently, multiple clinical studies of ICIs combined with chemotherapeutic drugs have been explored and proved effective. However, there are still crucial questions that are not well addressed, such as the optimal dose and schedule for a given combination may differ across disease indications, and the appropriate strategy of selecting patient population that can benefit from ICIs remains unclear. To facilitate more rational lung cancer ICIs therapy development, this review summarizes the immune-regulatory effects and related mechanisms of chemotherapeutic drugs and the clinical progress of ICIs and their combination with chemotherapies in lung cancer treatment.
The pregnane X receptor (PXR) not only plays an important role in cellular metabolism processes but also induces the resistance of hepatocellular carcinoma (HCC) cells to molecularly targeted drugs by mediating their metabolism and clearance by these cells. Endothelial PAS domain-containing protein 1 (EPAS-1) acts as a coactivator to regulate the transcription factor activity of PXR. In the present study, a microRNA that potentially targets EPAS-1, namely miR-3609, was identified using the miRDB tool.
The expression of miR-3609 and EPAS-1 was examined by qPCR. Lentiviral particles containing the full-length sequences of miR-3609 (pri-miR-3609) were prepared. The antitumor effect of antitumor agents was examined by the in vitro and in vivo assays.
The expression of miR-3609 was negatively correlated with that of EPAS-1 in both HCC clinical specimens and paired non-tumor specimens, and the effect of miR-3609 on the expression of EPAS-1 was confirmed by Western blot experiments. Overexpression of miR-3609 decreased the expression of EPAS-1 and, in turn, repressed the activation of the PXR pathway. miR-3609 decreased the transcription factor activation of PXR, repressed its recruitment to its target gene promoter regions, and decreased the expression of its target genes CYP3A4 and P-GP. link3 In addition, miR-3609 decelerated the metabolism and clearance of sorafenib in HCC cells and enhanced the antitumor effect of sorafenib in HCC cells.
Therefore, the results indicate that miR-3609 decreases the expression of EPAS-1 and enhances the sensitivity of HCC cells to sorafenib.
Therefore, the results indicate that miR-3609 decreases the expression of EPAS-1 and enhances the sensitivity of HCC cells to sorafenib.
Metabolomics has recently been applied in the field of oncology. In this study, we aimed to use metabolomics to explore biomarkers in peritoneal metastasis of gastric cancer.
Peritoneal lavage fluid (PLF) of 65 gastric cancer patients and related clinical data were collected from the First Hospital of Jilin University. The metabolic components were identified by liquid chromatography-mass spectrometry (LC-MS). Total ion current (TIC) spectra, principal component analysis (PCA), and the Student's
-test were used to identify differential metabolites in PLF. A support vector machine (SVM) was used to screen the differential metabolites in PLF with a weight of 100%. Cluster analysis was used to evaluate the similarity between samples. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic ability of the metabolites. Univariate and multivariate logistic regression analyses were used to identify potential risk factors for peritoneal metastasis of gastric cancer.
We found the differential levels of PLF metabolites by LC-MS, TIC spectra, PCA and the
-test.
