International journal of clinical and experimental pathology最新文献

[This corrects the article on p. 1224 in vol. 12, PMID: 31933937.].

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a five-year survival rate of 13%, the lowest among all malignant tumors. The work aims to use bioinformatics methods to mine Nerve-cancer crosstalk-related genes (NCCGs) in pancreatic cancer and evaluate their correlation with tumor stage and prognosis, thereby providing a new direction of development and experimental basis for pancreatic cancer treatment. This study included 185 individuals with PDAC from the TCGA database, together with clinical and RNA sequencing data. A review of prior studies revealed the mechanism of neural-cancer crosstalk and identified 42 neural-cancer crosstalk-related genes (NCCGs). Multivariate logistic regression analysis showed that NGFR (OR=39.076, 95% CI; P<0.05), CHRNB2 (OR=41.076, 95% CI; P<0.05), and CHRNA10 (OR=39.038, 95% CI; P<0.05) were identified as independent risk factors for PNI development. Pearson correlation analysis revealed that CHRNA10 was negatively connected with PDAC microsatellite instability, whereas CHRNA10, CHRNB2, and NGFR were negatively correlated with PDAC tumor mutation burden. The GEPIA database revealed that CHRNB2 expression was higher in stage I PDAC. The pancreatic cancer single-cell dataset PAAD_CRA001160 revealed that malignant tumor cells, ductal cells, endothelial cells and fibroblasts accounted for a large proportion in the tumor microenvironment of pancreatic cancer. Furthermore, the NGFR gene was shown to be more significantly expressed in various pancreatic cancer cells. Bioinformatics analysis was used to create a validated prognostic model of pancreatic cancer, which explored the critical mechanisms of neural-tumor interactions and revealed the potential of cancer-neural crosstalk-related genes as prognostic biomarkers and anti-tumor therapy targets.

The hepatocarcinoma (HCC) is the most important liver tumor. It represents 90% of liver cancer cases. One of the main problems is the limited prompt cancer diagnosis and the advanced stages where the chances of treatment are limited. The main diagnostic methods for HCC are imaging techniques and liver biopsy. With advances in technology, proteins as significant diagnostic biomarkers have increased. The objective of this review is to describe the role of Alpha-fetoprotein (AFP), Glipican 3 (GPC-3), and Kininogen 1 (KNG-1) as biomarkers for the diagnosis of hepatocellular carcinoma. A systematic search of studies was carried out in the literature and the diagnostic values of these proteins were compared. The results showed that the combined use of biomarkers increases the diagnostic capacity for the detection of hepatocellular carcinoma.

[This corrects the article on p. 6671 in vol. 7, PMID: 25400746.].

Background: Age-related macular degeneration (AMD) is a complex disease with a pathophysiology that remains incompletely understood. PCSK7 is closely related to the normal development of ocular tissues; however, the roles and mechanisms of PCSK7 in AMD have yet to be elucidated. Therefore, the purpose of this study was to investigate the specific manifestations of PCSK7 in AMD.

Methods: An AMD cell model was established by using hydrogen peroxide (H₂O₂)-treated ARPE-19 cells. The efficiency of PCSK7 overexpression was analyzed by western blotting (WB) and quantitative reverse transcription PCR (RT-qPCR). Subsequently, a Cell Counting Kit 8 (CCK-8) assay was employed to assess the proliferation of ARPE-19 cells, while flow cytometry and immunofluorescence were utilized to examine apoptosis. Iron accumulation and glutathione (GSH) levels in cells were measured using Enzyme-linked immunosorbent assay (ELISA), and WB was conducted to evaluate the expression of anti-ferroptosis protein. Finally, JC-1 staining was performed to assess mitochondrial membrane potential.

Results: Overexpressing of PCSK7 enhanced the proliferation and inhibited the apoptosis of ARPE-19 cells treated with H₂O₂. Additionally, increased PCSK7 expression suppressed intracellular iron levels and GSH content, thereby inhibiting the ferroptosis process. Furthermore, overexpression of PCSK7 restored mitochondrial membrane potential, alleviating H₂O₂-induced mitochondrial damage.

Conclusions: PCSK7 might be one of the targets for the treatment of AMD through the regulation of retinal epithelial cell death.

Background: Bromodomain and extra terminal domain (BET) proteins are important epigenetic regulators that promote the transcription of genes in the chromatin region associated with acetylated histones. Small molecule BET inhibitor JQ1 suppresses the biologic function of BET proteins in a variety of tumors and inhibits their proliferation.

Methods: We investigated the effect of JQ1 in the treatment of pancreatic cancer. In addition, we evaluated the expression level of BRD4 protein in pancreatic cancer tissues using the Gene Expression Profiling Interactive Analysis (GEPIA) and the Human protein Altas databases and analyzed the correlation between BRD4 and the clinicopathologic features and immune checkpoints of pancreatic adenocarcinoma using UALACN and TIMER databases.

Results: JQ1 significantly inhibited the proliferation of pancreatic adenocarcinoma (PAAD) cells and induced cell senescence but had little effect on Senescence-associated secretory phenotype (SASP). Interestingly, JQ1 inhibited the epithelial-mesenchymal transition (EMT) and Wnt signaling pathways.

Conclusions: These results provide a theoretical basis for new targets in the treatment of pancreatic cancer.

Objective: The aim of the present study was to investigate the expression of erythroblast transformation specific-1 related gene (ERG) in patients with glioblastoma (GB) before and after bevacizumab (Bev) therapy as a predictive and prognostic biomarker.

Methods: The present study used 58 GB tissues from 29 patients in 3 settings. Sixteen tumors were removed after neoadjuvant Bev administration (neoBev) and 13 represented newly diagnosed GB without previous Bev treatment (naïve Bev). Another 29 specimens of recurrence were obtained from salvage surgery or autopsy.

Results: Immunohistochemical analysis showed both vessel density (VD) and ERG score were decreased in neoBev compared with naïve Bev. VD and ERG score tended to be lower at recurrence than at initial surgery (P=0.0026 and P=0.1338, respectively). In the naïve Bev and neoBev cohorts, overall survival (OS) with high and low expressions of ERG was comparable (P=0.7516 and P=0.3862, respectively).

Conclusion: High expression of ERG in GB with naïveBev was significantly reduced with Bev, but not changed in refractoriness. Stratification of ERG expression levels might provide a useful predictive biomarker for GB treated with Bev.

Objective: Copper, an essential metal element for humans, plays vital functions in cancer prognosis and immunity. SLC31A1, a high-affinity copper transporter, helps regulate copper homeostasis and has been implicated in tumor prognosis through mechanisms such as drug resistance, autophagy, ferroptosis, and cuproptosis. However, the role of SLC31A1 in breast cancer (BRCA) and its association with tumor immune infiltration has not been fully elucidated. This study aimed to investigate the expression pattern of SLC31A1, its clinical significance, and its effect on tumor immune infiltration in BRCA.

Methods: We comprehensively analyzed multiple datasets, including Gene Expression Profiling Interaction Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), UALCAN, and Kaplan-Meier (KM) plotter, to assess the expression of SLC31A1 and its prognostic value in BRCA. Additionally, TIMER and TISIDB were used to explore the correlation between SLC31A1 expression and the extent of tumor immune infiltration.

Results: SLC31A1 was significantly upregulated in BRCA tissues compared to adjacent non-tumor tissues. Higher SLC31A1 expression levels were associated with poorer clinical outcome. Multivariate Cox regression analysis confirmed that SLC31A1 served as an independent prognostic indicator. Furthermore, SLC31A1 expression showed significant associations with various immunomodulators, chemokines, chemokine receptors, and tumor-infiltrating lymphocytes (TILs), including CD8+ T cells, CD4+ T cells, regulatory T cells (Tregs), follicular helper T cells (Tfh), neutrophils, M2 macrophages, tumor-associated macrophages (TAMs), and monocytes. These findings suggest that SLC31A1 may regulate macrophage polarization and T cell exhaustion in BRCA, contributing to immune evasion and poor prognosis.

Conclusion: Our study underscores the importance of further research to explore the therapeutic potential of targeting SLC31A1 and to uncover its additional roles in BRCA beyond the known mechanisms of drug resistance, autophagy, ferroptosis, and cuproptosis.

The use of medicinal plants in the management or prevention of diseases is one of the oldest human medicinal practices worldwide. Justicia carnea and Jatropha carcus are widely reported for their use in the management of blood disorders, hypertension, and diabetes.

Objective: The study aimed at evaluating the effects of hydroethanolic leaf extracts of Justicia carnea and Jatropha carcus on the biochemical, hematological, and histological parameters of apparently healthy rats.

Methodology: Thirty adult rats (n = 30) with an average weight of 153 g were randomly divided into six groups (A-F). Group A: negative control; Group B: positive control; Group C: Jatropha curcas (low dose); Group D: Jatropha curcas (high dose); Group E: Justicia carnea (low dose); and Group F: Justicia carnea (high dose). Standard and scientifically approved methods were used for sacrifice and laboratory diagnosis.

Results: The study shows a significant increase in body weight across groups administered with the leaf extracts. Elevated levels of serum creatinine were recorded in rats administered with both extracts, indicating nephrotoxicity. The study also observed an increase in alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase across groups, indicating hepatotoxicity. Both extracts caused an increase in white blood cell count and hemoglobin concentration, a significant reduction in bleeding time, increased prothrombin time, and partial thromboplastin time at high dosages. Total iron binding capacity and serum ferritin values were increased in high doses and were statistically significant at P<0.05. Histomorphology of both extracts shows hepatorenal toxicity at high concentrations and none in the lungs or heart. Oral administration of Justicia carnea and Jatropha carcus extracts at high concentrations is not safe for the liver and kidneys.

Conclusion: Biochemical parameters should be monitored regularly in humans exposed to both plants. Therefore, this study scientifically confirms and supports the traditional use of the leaves of Jatropha carcus and Justicia carnea to enhance hematological parameters.

[This retracts the article on p. 2989 in vol. 12, PMID: 31934136.].