Hepatocellular carcinoma (HCC) ranks fourth in cancer-related mortality worldwide. N1-methyladenosine (m1A), a methylation modification on RNA, is gaining attention for its role across diverse ...biological processes. However, m1A-related regulatory genes expression, its relationship with clinical prognosis, and its role in HCC remain unclear. In this study, we utilized The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database to investigate alterations within 10 m1A-related regulatory genes and observed a high mutation frequency (23/363). Cox regression analysis and least absolute shrinkage and selection operator were used to explore the association between m1A-related regulatory genes expression and HCC patient survival and identified four regulators that were remarkably associated with HCC patient prognosis. Additionally, an independent cohort from International Cancer Genome Consortium was studied to validate our discoveries and found to be consistent with those in the TCGA dataset. In terms of mechanism, gene set enrichment analysis linked these four genes with various physiological roles in cell division, the MYC pathway, protein metabolism, and mitosis. Kyoto Encyclopedia of Genes and Genomes analysis revealed that PI3K/Akt signaling pathway had potential relevance to m1A-related regulatory genes in HCC. These findings indicate that m1A-related regulatory genes may play crucial roles in regulating HCC progression and be exploited for diagnostic and prognostic purposes.
Objective
To investigate the association between microRNA-3615 (miR-3615) expression and the prognosis and clinicopathological features in patients with hepatocellular carcinoma (HCC).
Methods
We ...obtained clinicopathological and genomic data and prognostic information on HCC patients from The Cancer Genome Atlas (TCGA) database. We then analyzed differences in miR-3615 expression levels between HCC and adjacent tissues using SPSS software, and examined the relationships between miR-3615 expression levels and clinicopathological characteristics. We also explored the influence of miR-3615 expression levels on the prognosis of HCC patients using Kaplan–Meier survival curve analysis.
Results
Based on data for 345 HCC and 50 adjacent normal tissue samples, expression levels of miR-3615 were significantly higher in HCC tissues compared with adjacent tissues. MiR-3615 expression levels in HCC patients were negatively correlated with overall survival time and positively correlated with high TNM stage, serum Ki-67 expression level, and serum alpha-fetoprotein level. There were no significant correlations between miR-3615 expression and age, sex, and pathological grade.
Conclusion
MiR-3615 may be a promising new biomarker and prognostic factor for HCC.
Liver cancer is the fourth leading cause of cancer related mortality in the world, with hepatocellular carcinoma (HCC) representing the most common primary subtype. Two‐thirds of HCC patients have ...advanced disease when diagnosed, and for these patients, treatment strategies remain limited. In addition, there is a high incidence of tumor recurrence after surgical resection with the current treatment regimens. The development of novel and more effective agents is required. Cyclin‐dependent kinases (CDKs) constitute a family of 21 different protein kinases involved in regulating cell proliferation, apoptosis, and drug resistance, and are evaluated in preclinical and clinical trials as chemotherapeutics. To summarize and discuss the therapeutic potential of targeting CDKs in HCC, recent published articles identified from PubMed were comprehensively reviewed. The key words included hepatocellular carcinoma, cyclin‐dependent kinases, and CDK inhibitors. This review focuses on the emerging evidence from studies describing the genetic and functional aspects of CDKs in HCC. We also present an overview of CDK inhibitors that have shown efficacy in laboratory studies of HCC. Although many of the studies assessing CDK‐targeting therapies in HCC are at the preclinical stage, there is significant evidence that CDK inhibitors used alone or in combination with established chemotherapy drugs could have significant applications in HCC.
Hepatocellular carcinoma (HCC) is a common malignancy with high mortality worldwide. Despite advancements in diagnosis and treatment in recent years, there is still an urgent unmet need to explore ...the underlying mechanisms and novel prognostic markers. Anoikis has received considerable attention because of its involvement in the progression of human malignancies. However, the potential mechanism of anoikis-related genes (ANRGs) involvement in HCC progression remains unclear.
We use comprehensive bioinformatics analyses to determine the expression profile of ANRGs and their prognostic implications in HCC. Next, a risk score model was established by least absolute shrinkage and selection operator (Lasso) Cox regression analysis. Then, the prognostic value of the risk score in HCC and its correlation with clinical characteristics of HCC patients were further explored. Additionally, machine learning was utilized to identify the outstanding ANRGs to the risk score. Finally, the protein expression of DAP3 was examined on a tissue microarray (TMA), and the potential mechanisms of DAP3 in HCC was explored.
ANRGs were dysregulated in HCC, with a low frequency of somatic mutations and associated with prognosis of HCC patients. Then, nine ANRGs were selected to construct a risk score signature based on the LASSO model. The signature presented a strong ability of risk stratification and prediction for overall survival in HCC patients.Additionally, high risk scores were closely correlated with unfavorable clinical features such as advanced pathological stage, poor histological differentiation and vascular invasion. Moreover, The XGBoost algorithm verified that DAP3 was an important risk score contributor. Further immunohistochemistry determined the elevated expression of DAP3 in HCC tissues compared with nontumor tissues. Finally, functional analyses showed that DAP3 may promote HCC progression through multiple cancer-related pathways and suppress immune infiltration.
In conclusion, the anoikis-based signature can be utilized as a novel prognostic biomarker for HCC, and DAP3 may play an important role in the development and progression of HCC.
While the mechanisms of human cancer development are not fully understood, evidence of microRNA (miRNA, miR) dysregulation has been reported in many human diseases, including cancer. miRs are small ...noncoding RNA molecules that regulate posttranscriptional gene expression by binding to complementary sequences in the specific region of gene mRNAs, resulting in downregulation of gene expression. Not only are certain miRs consistently dysregulated across many cancers, but they also play critical roles in many aspects of cell growth, proliferation, metastasis, apoptosis, and drug resistance. Recent studies from our group and others revealed that miR-1 is frequently downregulated in various types of cancer. Through targeting multiple oncogenes and oncogenic pathways, miR-1 has been demonstrated to be a tumor suppressor gene that represses cancer cell proliferation and metastasis and promotes apoptosis by ectopic expression. In this review, we highlight recent findings on the aberrant expression and functional significance of miR-1 in human cancers and emphasize its significant values for therapeutic potentials.
Overexpression and/or hyperactivation of cyclin-dependent kinase 4 (CDK4) has been found in many types of human cancers, and a CDK4 specific inhibitor, palbociclib, has been recently approved by the ...FDA for the treatment of breast cancer. However, the expression and the therapeutic potential of CDK4 in osteosarcoma remain unclear. In the present study, CDK4 was found to be highly expressed in human osteosarcoma tissues and cell lines as compared with normal human osteoblasts. Elevated CDK4 expression correlated with metastasis potential and poor prognosis in osteosarcoma patients as determined by immunohistochemical analysis in a human osteosarcoma tissue microarray (TMA). CDK4 inhibition by either palbociclib or specific small interference RNA (siRNA) exhibited dose-dependent inhibition of osteosarcoma cell proliferation and growth, accompanied by suppression of the CDK4/6-cyclinD-Rb signaling pathway. Flow cytometry analysis showed that CDK4 knockdown arrested osteosarcoma cells in the G1 phase of the cell cycle and induced cell apoptosis. Furthermore, inhibition of CDK4 significantly decreased osteosarcoma cell migration in vitro determined by the wound healing assay. These data highlight that CDK4 may be a potential promising therapeutic target in the treatment of human osteosarcoma.
•CDK4 is highly expressed in human osteosarcoma tissues and cell lines.•Elevated CDK4 correlates with clinicopathological features of osteosarcoma patients.•CDK4 inhibition decreases osteosarcoma cell proliferation, growth and migration.•CDK4 inhibition induces osteosarcoma cell cycle arrest and apoptosis.•CDK4 may be a promising therapeutic target for osteosarcoma treatment.
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, leading to a large global cancer burden. Hepatocyte growth factor (HGF) and its high-affinity receptor, mesenchymal ...epithelial transition factor (c-Met), are closely related to the onset, progression, and metastasis of multiple tumors. The HGF/c-Met axis is involved in cell proliferation, movement, differentiation, invasion, angiogenesis, and apoptosis by activating multiple downstream signaling pathways. In this review, we focus on the function of the HGF/c-Met axis in HCC. The HGF/c-Met axis promotes the onset, proliferation, invasion, and metastasis of HCC. Moreover, it can serve as a biomarker for diagnosis and prognosis, as well as a therapeutic target for HCC. In addition, it is closely related to drug resistance during HCC treatment.
The purpose of this study was to evaluate the clinical diagnostic value of metagenomic next-generation sequencing (mNGS) for tuberculosis (TB).
This retrospective study included 52 patients with ...suspected TB infection. mNGS, targeted PCR, acid-fast staining and, T-SPOT.TB assay were performed on the specimen. The positive rate of mNGS and traditional detection methods was statistically analyzed. Pathological tests were performed when necessary.
In total, 52 patients with suspected of TB in this study were included in the analysis, and 31 patients were finally diagnosed with TB. Among 52 patients, 14 (26.9%) cases were positive for acid-fast staining. The positive rate of T-SPOT.TB assay in 52 patients was 73.1% (38/52). Among 52 patients, 39 (75%) were detected positive for
(
TB) by mNGS. Regarding the detection rate of MTB, mNGS were as high as 75% (39/52), whereas acid-resistant staining was only 26.9% (14/52), which showed a statistically significant difference (p<0.05). The positive rates of T-SPOT.TB assay and mNGS were not statistically significant (p>0.05). Of the 52 suspected TB patients, 24 had targeted PCR, of which 18 were PCR positive. In 24 patients, the positive rate of PCR was 75%, and the positive rate of mNGS was 100%, with statistical difference between them (p<0.05).
The detection rate of MTB by mNGS was higher than that by conventional acid-fast staining and PCR, but not statistically significant compared with T-SPOT.TB assay. As an adjunctive diagnostic technology, mNGS can be combined with traditional detection methods to play a guiding role in the diagnosis and treatment of TB.
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