The Phenotypic and Genotypic Spectrum of CSF1R-Related Disorder in China.

BACKGROUND: Colony-stimulating factor 1 receptor (CSF1R)-related disorder (CRD) is a rare autosomal dominant disease. The clinical and genetic characteristics of Chinese patients have not been elucidated. OBJECTIVE: The objective of the study is to clarify the core features and influence factors of CRD patients in China. METHODS: Clinical and genetic-related data of CRD patients in China were collected. Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Sundal MRI Severity Score were evaluated. Whole exome sequencing was used to analyze the CSF1R mutation status. Patients were compared between different sexes, mutation types, or mutation locations. RESULTS: A total of 103 patients were included, with a male-to-female ratio of 1:1.51. The average age of onset was (40.75 ± 8.58). Cognitive impairment (85.1%, 86/101) and parkinsonism (76.2%, 77/101) were the main clinical symptoms. The most common imaging feature was bilateral asymmetric white matter changes (100.0%). A total of 66 CSF1R gene mutants (22 novel mutations) were found, and 15 of 92 probands carried c.2381 T > C/p.I794T (16.30%). The MMSE and MoCA scores (17.0 [9.0], 11.90 ± 7.16) of female patients were significantly lower than those of male patients (23.0 [10.0], 16.36 ± 7.89), and the white matter severity score (20.19 ± 8.47) of female patients was significantly higher than that of male patients (16.00 ± 7.62). There is no statistical difference in age of onset between male and female patients. CONCLUSIONS: The core manifestations of Chinese CRD patients are progressive cognitive decline, parkinsonism, and bilateral asymmetric white matter changes. Compared to men, women have more severe cognitive impairment and imaging changes. c.2381 T > C/p.I794T is a hotspot mutation in Chinese patients. © 2024 International Parkinson and Movement Disorder Society.

hsa_circ_0000520 influences herceptin resistance in gastric cancer cells through PI3K-Akt signaling pathway.

BACKGROUND: To investigate whether hsa_circ_0000520 affects Herceptin resistance in gastric cancer by regulating the PI3K-AKT signaling. METHODS: The expression of hsa_circ_0000520 was detected by qRT-PCR in gastric cancer tissues and cell lines. A Herceptin-resistant gastric cancer cell was established. PcDNA and pcDNA-hsa_circ_0000520 were transfected into NCI-N87R cells and treated with Herceptin at a concentration of 10 µg/mL for 24 hours. MTT tested cell proliferation, and apoptosis was measured by flow cytometry. IGF-1 treatment was used to activate PI3K-Akt signaling. The expression levels of related proteins were detected. RESULTS: The expression of hsa_circ_0000520 was reduced in gastric cancer tissues and cell lines, and hsa_circ_0000520 in NCI-N87R cells was significantly lower than that of NCI-N87 cells. Compared with the CON group, the cell viability of the Herceptin group was significantly reduced, the apoptosis rate was significantly increased, the level of Bax protein was significantly increased, and the levels of Bcl-2, p-PI3K, and p-Akt protein were significantly reduced. Compared with the Herceptin + pcDNA group, the cell viability of the Herceptin + hsa_circ_0000520 group was significantly reduced, the apoptosis rate was significantly increased, the level of Bax protein was significantly increased, and the levels of p-PI3K and p-Akt proteins were significantly reduced. After IGF-1 treatment, the cell viability was significantly increased, the apoptosis rate was significantly reduced, the level of Bax protein was significantly reduced, and the level of Bcl-2 protein was significantly increased. CONCLUSION: Hsa_circ_0000520 overexpression may reverse the Herceptin resistance of gastric cancer cells by inhibiting the PI3K-Akt signaling pathway.

Comparative analysis of radiofrequency ablation and resection for colorectal liver metastases in caudate lobe: a retrospective study.

Objective: To assess the therapeutic efficiency of radiofrequency ablation (RFA) for colorectal liver metastases (CRLM) in the caudate lobe compared with that of surgical resection.Methods: After approved by institutional review board, we retrospectively reviewed 20 patients with caudate CRLM treated by RFA or resection between 2006 and 2017. Comparative analysis was performed based on the different therapies, including patient characteristics, therapeutic outcomes, recurrences, and survivals.Results: During the median follow-up of 7 years (range, 2 -11 years), no differences in complications and recurrences were found between RFA and surgery groups (p > .05). The median overall survival (OS) of patients after RFA and resection were 41 months (95% confidence interval (CI) 23.5-70.5) and 54 months (95% CI 31.1-77.7), respectively (p = .627, hazard radio (HR) 0.7, 95% CI 0.2-2.6). However, OS of resection group was better than that of RFA group for large caudate CRLMs (>3 cm) (p = .042, HR 4.4, 95% CI 0.6-32.6).Conclusions: RFA is a feasible, safe, and effective treatment for CRLM in the caudate. Surgical resection revealed superior outcomes in the treatment of caudate CRLMs, particularly in cases with a hepatic tumor size >3 cm.

Integrating p53-associated genes and infiltrating immune cell characterization as a prognostic biomarker in multiple myeloma.

Background: Tumor genetic anomalies and immune dysregulation are pivotal in the progression of multiple myeloma (MM). Accurate patient stratification is essential for effective MM management, yet current models fail to comprehensively incorporate both molecular and immune profiles. Methods: We examined 776 samples from the MMRF CoMMpass database, employing univariate regression with LASSO and CIBERSORT algorithms to identify 15 p53-related genes and six immune cells with prognostic significance in MM. A p53-TIC (tumor-infiltrating immune cells) classifier was constructed by calculating scores using the bootstrap-multicox method, which was further validated externally (GSE136337) and through ten-fold internal cross-validation for its predictive reliability and robustness. Results: The p53-TIC classifier demonstrated excellent performance in predicting the prognosis in MM. Specifically, patients in the p53low/TIChigh subgroup had the most favorable prognosis and the lowest tumor mutational burden (TMB). Conversely, those in the p53high/TIClow subgroup, with the least favorable prognosis and the highest TMB, were predicted to have the best anti-PD1 and anti-CTLA4 response rate (40 %), which can be explained by their higher expression of PD1 and CTLA4. The three-year area under the curve (AUC) was 0.80 in the total sample. Conclusions: Our study highlights the potential of an integrated analysis of p53-associated genes and TIC in predicting prognosis and aiding clinical decision-making in MM patients. This finding underscores the significance of comprehending the intricate interplay between genetic abnormalities and immune dysfunction in MM. Further research into this area may lead to the development of more effective treatment strategies.

circZC3HAV1 Regulates TBC1D9 to Affect the Biological Behavior of Colorectal Cancer Cells.

Background: Colorectal cancer (CRC) is one of the most frequently diagnosed cancers all over the world, which accounts for a large proportion of cancer-associated deaths. The regulatory function of circular RNAs (circRNAs) has been affirmed in diverse cancers. circ_0082628, named circRNA zinc finger CCCH-type containing antiviral 1 (circZC3HAV1), has been discovered to be significantly downregulated in CRC tissues. Nevertheless, the function and mechanism of circZC3HAV1 in CRC remain unclear. Purpose: We targeted at studying the specific role and mechanism of circZC3HAV1 in CRC cells. Methods: The expression of the genes was detected by quantitative real-time polymerase chain reaction (qPCR). The binding relationship among different genes was verified by mechanism assays. Functional assays were carried out to reveal the role of different RNAs in CRC cell malignant behaviors. Results: circZC3HAV1 was significantly downregulated in CRC cells. circZC3HAV1 overexpression hampered CRC cell migratory and invasive abilities. As for the mechanism, circZC3HAV1 competitively bound with microRNA-146b-3p (miR-146b-3p) to enhance the expression of TBC1 domain family member 9 (TBC1D9). Rescue assays demonstrated circZC3HAV1 sponged miR-146b-3p and upregulated TBC1D9 to restrict migration and invasion of CRC cells. Conclusion: circZC3HAV1 could upregulate TBC1D9 via absorbing miR-146b-3p, consequently inhibiting migratory and invasive capabilities of CRC cells.

Long non-coding RNA-ZNF281 promotes cancer cell migration and invasion in gastric cancer via downregulation of microRNA-124.

It has previously been determined that long non-coding (lnc)RNA-zinc finger protein (ZNF)281 serves an oncogenic role in breast cancer; however, the role of lncRNA-ZNF281 in other cancer types is yet to be elucidated. The present study aimed to analyze the role of ZNF281 in gastric cancer by characterizing its activity in cancerous tissues and normal tissues using RT-qPCR. Overexpression experiments were also performed to investigate the interaction between ZNF281 and miR-124, and Transwell assays were conducted to analyze cell invasion and migration. The present study revealed that lncRNA-ZNF281 was upregulated, and that microRNA (miR)-124 was downregulated, in cancerous tissues compared with that in the paired adjacent healthy tissues of patients with gastric cancer. In addition, the expression levels of lncRNA-ZNF281 and miR-124 exhibited a significant inverse association. Furthermore, in vitro cell experiments determined that lncRNA-ZNF281 overexpression resulted in miR-124 inhibition, yet miR-124 overexpression did not influence lncRNA-ZNF281 expression. lncRNA-ZNF281 expression level was also associated with the clinical stage of the patient. Bioinformatics analysis revealed that lncRNA-ZNF281 may target the base pairs in the hairpin loop of the miR-124 precursor. Subsequent in vitro cell experiments indicated that lncRNA-ZNF281 overexpression resulted in promoting the migration and invasiveness of gastric cancer cells, while miR-124 over-expression led to its inhibition. In addition, miR-124 overexpression partially recovered the effects of lncRNA-ZNF281 overexpression. Therefore, lncRNA-ZNF281 may promote cancer cell migration and invasion in gastric cancer via downregulation of miR-124.