No abstract

Background: Breast cancer (BRCA) is the most common malignancy with high heterogeneity in women, and the prognostic prediction for BRCA has remained poor. Ferroptosis, a recently identified iron-dependent form of programmed cell death, plays a significant role in BRCA treatment. Some BRCA cell lines are proven to be sensitive to ferroptosis, and some ferroptosis-related genes have been identified as divers or suppressors in the progress of BRCA. This study aimed to explore the prognostic value of ferroptosis-related genes in BRCA.Methods: A ferroptosis-related gene list, messenger RNA (mRNA) gene expression of BRCA patients, and corresponding clinicopathological data were collected from public databases. The patients of the Cancer Genome Atlas (TCGA) were identified as the training cohort, and the ones of the Gene Expression Omnibus (GEO) were looked as the validation cohort. Univariate Cox regression analysis was utilized to identify prognostic ferroptosis-related genes, and subsequent multivariate analysis further screened out important genes to establish a prognostic model. Receiver operating characteristic (ROC) curves were used to validate the model in both internal and external cohorts. Functional analysis was generated to evaluate the potential correlation between tumor immunity and ferroptosis-related genes in BRCA.Results: A ferroptosis-related gene signature stratifying patients into 2 risk score groups was established based on the TCGA cohort, and validated in the GEO cohort. Patients with lower risk scores had better overall survival (OS) compared to those with higher risk scores (P<0.001, TCGA cohort; P<0.05, GEO cohort). The risk score was independently associated with the OS of BRCA patients (P<0.001, TCGA cohort; P<0.05, GEO cohort). The area under the curves (AUCs) of the model in the training and validation cohorts were all around 0.7. Immune-related biological pathways and immune status were significantly different between the 2 divided risk groups. Conclusions:The novel prognostic model composed of 9 ferroptosis-related genes accurately predicts the survival of BRCA patients. It might provide a new sight for ferroptosis-related BRCA therapy.

Purpose: Colon cancer is the most common malignant tumor in the intestine. Abnormal Carboxylesterases 3 (CES3 expression had been reported to be correlated to multiple tumor progression.However, the association among CES3 expression and prognostic value and immune effects in colonic adenocarcinoma (COAD) were unclear.Patients and methods: The transcription pro le of CES3 were downloaded from The Cancer Genome Atlas (TCGA). The CES3 protein expression and the prognostic value were veri ed based on tissue microarray data. The Cancer immune group Atlas (TCIA), Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and the GSE78220 immunotherapy cohort were used to forecast immunotherapy e cacy. Finally, a prognostic immune signature was constructed and veri ed.Results: Compared with normal colon tissues, the expression of mRNA and protein levels of CES3 were downregulated in tumor tissues. CES3 expression was associated with TIICs. Hihg-CES3 COAD patients had better e cacy of concurrent immunotherapy. CES3-related immune genes (CRIs) were identi ed and were then used to construct prognostic immune signature and had been successfully veri ed in GES39582.Conclusion: CES3 might be a potential immune-related gene and promising prognostic biomarker in COAD. downloaded from TCGA website (The Cancer Genome Atlas, https://portal.gdc.cancer.gov/, accessed on March 21, 2022)(17). GSE39582 was obtained from the GEO database (Gene Expression Omnibus, https://www.ncbi.nlm.nih.gov/geo/) to validate the TCGA-COAD signature. Patients who missing complete transcriptome information and clinically relevant information were excluded before analysis, and R software was used for data cleaning. The CRIs were acquired from IMMPORT database (https://immport.niaid.nih.gov) (18). The data in this study were derived from public databases, so there were no ethical tissues involved. Analysis of differential CES3 expressionCOAD patients were divided into high-and low-CES3 groups based on the median value of CES3 mRNA expression in the TCGA database. R "limma" package was applied to analyze the difference of CES3 mRNA expression between normal and tumor tissues. The R "survival" package was used to study the relevance between overall survival (OS) and CES3 expression. The Cox regression model was used to gure up and visualize the corresponding clinical information and OS in the forest package. Analysis of functional biopathway with CES3The R "ggplot2" and "cluster Pro ler" packages were used to the Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Furthermore, Gene Set Enrichment Analysis (GSEA)(19) was used to analyze the potential pathways of CES3 related top enriched genes.Adjusted p values < 0.05, the enrichment of standardized scores (NES) ≥ 1, and the false discovery rate (FDR) ≥ 0.25 are signi cant difference.

BRAF non-V600 mutations are a distinct molecular subset of colorectal cancer (CRC) that has little to no clinical similarity to the BRAF V600 mutations. It is generally considered that the BRAF non-V600 mutations correlate with better survival of CRC patients. In this report, we present an unusual case of that a midlife female patient who was initially diagnosed with stage IIIC colon cancer, and multiple metastases were found 25 months after radical surgery. Next-generation sequencing (NGS) revealed the BRAF p.N581I (c.1742A&gt;T) mutation. She received chemotherapy, targeted therapy, and immunotherapy. However, the disease progressed rapidly with rare metastasis of the bone and cerebellum. This case highlights that the BRAF non-V600 mutations, such as BRAF p.N581I mutant, may lead to resistance to epidermal growth factor receptor (EGFR) inhibitors and result in a rapid course in colorectal cancer. The role of BRAF p.N581I mutation in colorectal cancer demands more attention.