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Des-γ-carboxy Prothrombin in hepatocellular carcinoma post-operative recurrence risk evaluation
While the value of Des-γ-carboxy prothrombin in hepatocellular carcinoma diagnosis has been widely acknowledged, whether or how Des-γ-carboxy prothrombin could be used in recurrence evaluation remains largely unexplored.
Multiomic quantification of the KRAS mutation dosage improves the preoperative prediction of survival and recurrence in patients with pancreatic ductal adenocarcinoma
Most cancer mutation profiling studies are laboratory-based and lack direct clinical application. For clinical use, it is necessary to focus on key genes and integrate them with relevant clinical variables. We aimed to evaluate the prognostic value of the dosage of the KRAS G12 mutation, a key pancreatic ductal adenocarcinoma (PDAC) variant and to investigate the biological mechanism of the prognosis associated with the dosage of the KRAS G12 mutation. In this retrospective cohort study, we analyzed 193 surgically treated patients with PDAC between 2009 and 2016. RNA, whole-exome, and KRAS-targeted sequencing data were used to estimate the dosage of the KRAS G12 mutant. Our prognostic scoring system included the mutation dosage from targeted sequencing ( > 0.195, 1 point), maximal tumor diameter at preoperative imaging ( > 20 mm, 1 point), and carbohydrate antigen 19-9 levels ( > 150 U/mL, 1 point). The KRAS mutation dosage exhibited comparable performance with clinical variables for survival prediction. High KRAS mutation dosages activated the cell cycle, leading to high mutation rates and poor prognosis. According to prognostic scoring systems that integrate mutation dosage with clinical factors, patients with 0 points had superior median overall survival of 97.0 months and 1-year, 3-year, and 5-year overall survival rates of 95.8%, 70.8%, and 66.4%, respectively. In contrast, patients with 3 points had worse median overall survival of only 16.0 months and 1-year, 3-year, and 5-year overall survival rates of 65.2%, 8.7%, and 8.7%, respectively. The incorporation of the KRAS G12 mutation dosage variable into prognostic scoring systems can improve clinical variable-based survival prediction, highlighting the feasibility of an integrated scoring system with clinical significance.
SREBF1-based metabolic reprogramming in prostate cancer promotes tumor ferroptosis resistance
Metabolic reprogramming in prostate cancer has been widely recognized as a promoter of tumor progression and treatment resistance. This study investigated its association with ferroptosis resistance in prostate cancer and explored its therapeutic potential. In this study, we identified differences in the epithelial characteristics between normal prostate tissue and tissues of various types of prostate cancer using single-cell sequencing. Through transcription factor regulatory network analysis, we focused on the candidate transcription factor, SREBF1. We identified the differences in SREBF1 transcriptional activity and its association with ferroptosis, and further verified this association using hdWGCNA. We constructed a risk score based on SREBF1 target genes associated with the biochemical recurrence of prostate cancer by combining bulk RNA analysis. Finally, we verified the effects of the SREBPs inhibitor Betulin on the treatment of prostate cancer and its chemosensitization effect. We observed characteristic differences in fatty acid and cholesterol metabolism between normal prostate tissue and prostate cancer tissue, identifying high transcriptional activity of SREBF1 in prostate cancer tissue. This indicates that SREBF1 is crucial for the metabolic reprogramming of prostate cancer, and that its mediated metabolic changes promoted ferroptosis resistance in prostate cancer in multiple ways. SREBF1 target genes are associated with biochemical recurrence of prostate cancer. Finally, our experiments verified that SREBF1 inhibitors can significantly promote an increase in ROS, the decrease in GSH, and the decrease in mitochondrial membrane potential in prostate cancer cells and confirmed their chemosensitization effect in vivo. Our findings highlighted a close association between SREBF1 and ferroptosis resistance in prostate cancer. SREBF1 significantly influences metabolic reprogramming in prostate cancer cells, leading to ferroptosis resistance. Importantly, our results demonstrated that SREBF1 inhibitors can significantly enhance the therapeutic effect and chemosensitization of prostate cancer, suggesting a promising therapeutic potential for the treatment of prostate cancer.
Nationwide analysis of sex differences in waiting times for cataract surgery in Sweden between 2010 and 2022
Sex-based disparities in healthcare access remain a global challenge. We aimed to investigate differences in waiting times for cataract surgery between males and females in Sweden, hypothesizing that such disparities might persist even within a universal healthcare system.
Intraoperative frozen section examination for penile cancer surgery: a systematic review
Penile cancer (PeCa) is rare but aggressive and life changing. Penile-preserving surgery (PPS) allows length preservation for sexual activity and normal voiding. Intraoperative frozen section examination (FSE) of resection margins helps to decide on how much penile tissue is excised. Oncological outcomes and diagnostic accuracy of FSE to date, however, are not well documented. The objective of this systematic review was to evaluate the efficacy of FSE in the treatment of PeCa and its impact on oncological outcomes. A systematic review was conducted with reference to the PRISMA statement. Studies published from 2009 to 2024 were identified through a search conducted between 1975 and 2024. The search yielded 7 studies involving 574 patients. Intraoperative FSE had a high percentage of accuracy, with a mean accuracy of 95.4% and a range of 92.9–99.4%. The mean values of sensitivity, specificity, positive predictive value, and negative predictive values were 71.4%, 99.9%, 98.8%, and 96.5%, respectively. Functional outcomes with PPS were encouraging, especially in terms of sexual function. The average local recurrence rate was 7.9%. There is a paucity of data on PeCa FSE in the literature. However, it appears that FSE is accurate and can be helpful in guiding surgeons intraoperatively when performing PPS.
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