Identification of clinical prognosis features and significant DNA methylation regulation in pineoblastoma.

BACKGROUND: Pineoblastoma (PB) represents a great challenge for clinical management due to lack of a specific therapeutic regimen. This study aims to identify relevant prognostic factors and potential treatment targets by mining public databases. METHODS: The clinical characteristics and survival data of PB patients were obtained from the SEER database between 2000 and 2019 for Cox regression analysis and nomogram construction. The PB's DNA methylation data was acquired from two GEO datasets, GSE133801 and GSE215240, for bioinformatics analysis. RESULTS: Of 383 PB patients, Cox univariate analysis unveiled that male gender (p = 0.017), age younger than 3 years at diagnosis (p < 0.001) and absence of radiotherapy (p < 0.001) correlated with poorer overall survival (OS), the subsequent multivariate analysis confirmed sex (p = 0.036), age (p < 0.001) and radiotherapy (p = 0.005) as independent prognostic factors for OS. A nomogram showed robust predictive accuracy as evidenced by AUC values (1-year OS: 0.774, 3-year OS: 0.692, 5-year OS: 0.643). DNA methylation analysis observed tumor hypomethylation, notably in promoter regions. Later, the GO enrichment analysis of aberrantly methylated genes indicated associations with embryonic organ development, cellular membrane composition and DNA-binding transcription, while KEGG analysis revealed enrichment in tumor-associated MAPK, calcium and RAS signaling pathways. CONCLUSIONS: The prognosis of PB is closely associated with sex, age and receipt of radiotherapy, potentially linked to aberrations in the RAS and MAPK signaling pathways. The individual case suggests that dasatinib and trametinib are potential targeted therapies for improving PB prognosis.

Identification of a ferroptosis-related gene signature for the prognosis of pediatric neuroblastoma.

Background: Ferroptosis-related genes are correlated with the prognosis of patients with neuroblastoma (NB) remains unknown. This study aims to establish a prognostic ferroptosis-related gene model for predicting prognostic value in pediatric NB patients. Methods: The gene expression array and clinical characteristics of NB were downloaded from a public database. Correlations between ferroptosis-related genes and drug responses were analyzed by Childhood Cancer Therapeutics. The prognostic model was constructed by least absolute shrinkage and selection operator (LASSO) Cox regression and was validated in NB patients from the ICGC cohort. The survival analysis was performed by Cox regression analysis. single-sample gene set enrichment analysis (ssGSEA) was used to quantify the immune cell infiltration correlation. Results: Overall, 70 genes were identified as ferroptosis-related differentially expressed genes (DEGs) from 247 samples. Then, 13 ferroptosis-related genes were correlated with OS in the univariate Cox regression analysis. Five prognostic ferroptosis-related DEGs (pFR-DEGs) (STEAP3, MAP1LC3A, ULK2, MTOR and TUBE1), which were defined as the intersection of DEGs and prognostic ferroptosis-related genes, were identified and utilized to construct the prognostic signature. The correlation between five pFR-DEGs and drug responses was analyzed, and the box plots indicated that MTOR gene expression was highest, suggesting that MTOR expression is related to progressive NB disease. The receiver operating characteristic (ROC) curve showed that the model had moderate predictive power. The survival analysis indicated that the high-risk group had poor overall survival (OS) (P=2.087×10-06). Univariate and multivariate analyses identified the risk score as a significant prognostic risk factor [P=0.003, hazard ratio (HR) =1.933]. Immune cell infiltration correlation analysis showed that the high-risk group was related to more immune cells. Conclusions: The present study indicated a difference in ferroptosis-related gene expression between low- and high-risk NB patients. The ferroptosis-related signature could serve as a prognostic prediction tool. Additionally, immune infiltration might play an important role in different risk groups for NB patients.

Clinical predictors of pathological good response in locally advanced rectal cancer.

PURPOSE: The aim of this study was to identify the clinical predictors of pathological good response (PGR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) to clarify the indications for local excision. METHODS AND MATERIALS: A total of 173 patients with LARC (cT3-4/N +) who were treated with nCRT followed by surgery were enrolled in our retrospective study. Patients were categorized into two groups according to the different tumor responses of surgical pathology. Stage ypT0-1N0 was defined as the group with PGR, and stage ypT2-4N0/ypTanyN + was the defined as the pathological poor response (PPR) group, and the potential predictors were compared. RESULTS: Of 173 patients, PGR was achieved in 57 patients (32.95%). The distance from the inferior margin of the tumor to the anal verge, cT classification, pretreatment carcinoembryonic antigen (CEA) and the interval from the end of radiation to surgery were correlated with pathological response. In the multivariate analysis, the distance from anal verge < 5 cm (OR = 0.443, p = 0.019), pretreatment CEA < 5 ng/mL (OR = 0.412, p = 0.015) and the interval from the end of radiation to surgery ≥ 84 days (OR = 2.652, p = 0.005) were independent predictors of PGR. CONCLUSIONS: The distance from the inferior margin of the tumor to the anal verge, pretreatment CEA and the interval from the end of radiation to surgery were significant predictors of PGR in LARC. A prospective study is needed to further validate these results in the future.