Journal of Oncology最新文献

An inverse association between use of antiepileptic drugs (AEDs) and prostate cancer (PCa) has been suggested, putatively due to the histone deacetylases inhibitory (HDACi) properties of the AEDs. In a case-control study in Prostate Cancer data Base Sweden (PCBaSe), PCa cases diagnosed between 2014 and 2016 were matched to five controls by year of birth and county of residence. AED prescriptions were identified in the Prescribed Drug Registry. Odds ratios (ORs) and 95% confidence intervals for risk of PCa were estimated using multivariable conditional logistic regression, adjusted for civil status, education level, Charlson comorbidity index, number of outpatient visits, and cumulative duration of hospital stay. Dose responses in different PCa risk categories and HDACi properties of specific AED substances were further explored. 1738/31591 (5.5%) cases and 9674/156802 (6.2%) controls had been exposed to AED. Overall, users of any AED had a reduced risk of PCa as compared to nonusers (OR: 0.92; 95% CI: 0.87-0.97) which was attenuated by adjustment to healthcare utilisation. A reduced risk was also observed in all models for high-risk or metastatic PCa in AED users compared to nonusers (OR: 0.89; 95% CI: 0.81-0.97). No significant findings were observed for dose response or HDACi analyses. Our findings suggest a weak inverse association between AED use and PCa risk, which was attenuated by adjustment for healthcare utilisation. Moreover, our study showed no consistent dose-response pattern and no support for a stronger reduction related to HDAC inhibition. Further studies focusing on advanced PCa and PCa treatments are needed to better analyse the association between use of AED and risk of PCa.

Hepatocellular carcinoma (HCC) is a highly lethal and heterogeneous malignancy with multiple genetic alternations and complex signaling pathways. The complexity and multifactorial nature of HCC pose a tremendous challenge regarding its diagnosis and treatment. Emerging evidence has indicated an important regulatory role of epigenetic modifications in HCC initiation and progression. Epigenetic modifications are stably heritable gene expression traits caused by changing the accessibility of chromatin structure and genetic activity without alteration in the DNA sequence and have been gradually recognized as a hallmark of cancer. In addition, accumulating data suggest a potential value of altered hydroxymethylation in epigenetic modifications and therapeutics targeting the epigenetically mediated regulation. As such, probing the epigenetic field in the era of precision oncology is a valid avenue for promoting the accuracy of early diagnosis and improving the oncological prognosis of HCC patients. This review focuses on the diagnostic performance and clinical utility of 5-hydroxymethylated cytosine, the primary intermediate product of the demethylation process, for early HCC diagnosis and discusses the promising applications of epigenetic-based therapeutic regimens for HCC.

Long noncoding (lnc) RNAs regulate cancer progression. However, the importance of lncRNAs and how they are regulated in colorectal cancer (CRC) are unclear. We aim to evaluate the function of lncRNA ADAMTS9-AS2 in CRC and its fundamental mechanism. Levels of ADAMTS9-AS2, miR-27a-3p, and B-cell translocation gene 2 (BTG2) were measured by qPCR. Cell viability was analyzed by CCK-8 and colony formation. Migration and invasion were tested by transwell assay. The interactions among ADAMTS9-AS2, miR-27a-3p, BTG2, and YTHDF2 were analyzed by luciferase test, immunoblotting, RNA pull-down, or RNA immunoprecipitation (RIP). An animal model was adopted to assess ADAMTS9-AS2's function. Overexpressing ADAMTS9-AS2 inhibited cell migration, invasion, colony formation capacity, and proliferation in vitro. The direct targeting of miR-27a-3p by ADAMTS9-AS2 abrogated the latter's effect in CRC cells. BTG2 was identified a target of miR-27a-3p, and silencing BTG2 weakened miR-27a-3p's effect. Knocking down ADAMTS9-AS2 abolished sh-YTHDF2's inhibitory effect on cell proliferation and invasion. Finally, overexpressing ADAMTS9-AS2 restrained xenograft growth. M6A reader YTHDF2-mediated degradation of ADAMTS9-AS2 promotes colon carcinogenesis via miR-27a-3p/BTG2 axis.

In elderly men, prostate cancer is a leading cause of death. Tumor cells require more energy to progress than normal cells, and this energy is mainly dependent on the large amount of ATP support generated by lipid metabolism. Therefore, in this study, we focused on long noncoding RNAs related to lipid metabolism in prostate cancer to discover the biological mechanisms of lipid metabolism regulation. The TCGA-PRAD cohort was used in this study for computational biology analysis. In lipid metabolism biological pathways, 1959 long noncoding RNAs were identified by Pearson correlation coefficient analysis of protein-coding genes, then univariate regression with P values fewer than 0.05. We further identified 784 lncRNAs that were lipid metabolism-related lncRNAs considered to have prognostic value for disease-free survival. Subsequently, we constructed two lncRNA expression patterns of lipid metabolism based on these lncRNAs by nonnegative matrix dimensionality reduction. These two expression patterns showed significant differences in disease-free survival curves for those diagnosed with prostate cancer. We found significant differences in mRNA surveillance pathway and mRNA processing between C1 and C2 groups based on the WGCNA method to explore the biological characteristics of these two expression patterns. Finally, we constructed a disease-free survival (PFS) model based on these lncRNAs. The results identified lncRNAs involved in lipid metabolism and revealed differences in their expression patterns. Additionally, the results offer candidate ideas and approaches concerning the precision treatment of prostate cancer by studying lipid metabolism by candidate long noncoding RNAs.

[This retracts the article DOI: 10.1155/2022/4537021.].

Background: Approximately 10% of cancer patients worldwide have colorectal cancer (CRC), a prevalent gastrointestinal malignancy with substantial mortality and morbidity. The purpose of this work was to investigate the APOC1 gene's expression patterns in the CRC tumor microenvironment and, using the findings from bioinformatics, to assess the biological function of APOC1 in the development of CRC.

Methods: The TCGA portal was employed in this investigation to find APOC1 expression in CRC. Its correlation with other genes and clinicopathological data was examined using the UALCAN database. To validate APOC1's cellular location, the Human Protein was employed. In order to forecast the relationship between APOC1 expression and prognosis in CRC patients, the Kaplan-Meier plotter database was used. TISIDB was also employed to evaluate the connection between immune responses and APOC1 expression in CRC. The interactions of APOC1 with other proteins were predicted using STRING. In order to understand the factors that contribute to liver metastasis from CRC, single-cell RNA sequencing (scRNA-seq) was done on one patient who had the disease. This procedure included sampling preoperative blood and the main colorectal cancer tissues, surrounding colorectal cancer normal tissues, liver metastatic cancer tissues, and normal liver tissues. Finally, an in vitro knockdown method was used to assess how APOC1 expression in tumor-associated macrophages (TAMs) affected CRC cancer cell growth and migration.

Results: When compared to paracancerous tissues, APOC1 expression was considerably higher in CRC tissues. The clinicopathological stage and the prognosis of CRC patients had a positive correlation with APOC1 upregulation and a negative correlation, respectively. APOC1 proteins are mostly found in cell cytosols where they may interact with APOE, RAB42, and TREM2. APOC1 was also discovered to have a substantial relationship with immunoinhibitors (CD274, IDO1, and IL10) and immunostimulators (PVR, CD86, and ICOS). According to the results of scRNA-seq, we found that TAMs of CRC tissues had considerably more APOC1 than other cell groups. The proliferation and migration of CRC cells were impeded in vitro by APOC1 knockdown in TAMs.

Conclusion: Based on scRNA-seq research, the current study shows that APOC1 was overexpressed in TAMs from CRC tissues. By inhibiting APOC1 in TAMs, CRC progression was reduced in vitro, offering a new tactic and giving CRC patients fresh hope.

High-temperature requirement protein A2 (HtrA2), a mitochondrial protein, is related to apoptosis regulation. However, the role of HtrA2 in hepatocellular carcinoma (HCC) remains unclear. In the present study, we explored the prognostic value and expression pattern of HtrA2 in HCC and confirmed its independent value for predicting outcomes via Cox analyses. LinkedOmics and GEPIA2 were used to construct the coexpression and functional networks of HtrA2. Additionally, the data obtained from TCGA was analyzed to investigate the relationship between the infiltration of immune cells and HtrA2 mRNA expression. Finally, the expression pattern of HtrA2 in HCC was confirmed by wet-lab experiments. The results showed high HtrA2 expression (P < 0.001) presented in tumor tissues in TCGA-HCC. Moreover, high HtrA2 expression was confirmed to be associated with poor HCC patient survival (P < 0.05). HtrA2 has also been recognized as an essential risk factor for overall survival (P=0.01, HR = 1.654, 95% CI 1.128-2.425), disease-specific survival (P=0.004, HR = 2.204, 95% CI 1.294-3.753), and progression-free interval (P=0.007, HR = 1.637, 95% CI 1.145-2.341) of HCC. HCC patients with low HtrA2 methylation had worse overall survival than patients with high methylation (P=0.0019). Functional network analysis suggests that HtrA2 regulates mitochondrial homeostasis through pathways involving multiple microRNAs and transcription factors in HCC. In addition, HtrA2 expression correlated with infiltrating levels of multiple immune cell populations. At last, increased expression of HtrA2 in HCC was confirmed using wet-lab experiments. Our study provides evidence that the upregulation of HtrA2 in HCC is an independent predictor of prognosis. Our results provide the foundation for further study on the roles of HtrA2 in HCC tumorigenesis.

Background: For elderly patients with primary spinal tumors, surgery is the best option for many elderly patients, in addition to palliative care. However, due to the unique physical function of elderly patients, the short-term prognosis is often unpredictable. It is therefore essential to develop a novel nomogram as a clinical aid to predict the risk of early death for elderly patients with primary spinal tumors who undergo surgery.

Materials and methods: In this study, clinical data were obtained from 651 patients through the SEER database, and they were retrospectively analyzed. Logistic regression analyses were used for risk-factor screening. Predictive modeling was performed through the R language. The prediction models were calibrated as well as evaluated for accuracy in the validation cohort. The receiver operating characteristic (ROC) curve and the decision curve analysis (DCA) were used to evaluate the functionality of the nomogram.

Results: We identified four separate risk factors for constructing nomograms. The area under the receiver operating characteristic curve (training set 0.815, validation set 0.815) shows that the nomogram has good discrimination ability. The decision curve analysis demonstrates the clinical use of this nomogram. The calibration curve indicates that this nomogram has high accuracy. At the same time, we have also developed a web version of the online nomogram for clinical practitioners to apply.

Conclusions: We have successfully developed a nomogram that can accurately predict the risk of early death of elderly patients with primary spinal tumors undergoing surgery, which can provide a reference for clinicians.

Background: Many studies have found that chromatin regulators (CRs) are correlated with tumorigenesis and disease prognosis. Here, we attempted to build a new CR-related gene model to predict breast cancer (BC) survival status.

Methods: First, the CR-related differentially expressed genes (DEGs) were screened in normal and tumor breast tissues, and the potential mechanism of CR-related DEGs was determined by function analysis. Based on the prognostic DEGs, the Cox regression model was applied to build a signature for BC. Then, survival and receiver operating characteristic (ROC) curves were performed to validate the signature's efficacy and identify its independent prognostic value. The CIBERSORT and tumor immune dysfunction and exclusion (TIDE) algorithms were used to assess the immune cells infiltration and immunotherapy efficacy for this signature, respectively. Additionally, a novel nomogram was also built for clinical decisions.

Results: We identified 98 CR-related DEGs in breast tissues and constructed a novel 6 CR-related gene signature (ARID5A, ASCL1, IKZF3, KDM4B, PRDM11, and TFF1) to predict the outcome of BC patients. The prognostic value of this CR-related gene signature was validated with outstanding predictive performance. The TIDE analysis revealed that the high-risk group patients had a better response to immune checkpoint blockade (ICB) therapy.

Conclusion: A new CR-related gene signature was built, and this signature could provide the independent predictive capability of prognosis and immunotherapy efficacy for BC patients.