Role of the KRT7 Biomarker in Immune Infiltration and Paclitaxel Resistance in Ovarian.

Context: Paclitaxel (PTX) resistance is often associated with poor outcomes for patients with ovarian cancer (OC), but its mechanism is unknown. Clinicians are increasingly using immunotherapy in the management of OC, and the ability to assess tumor-immune interactions and identify effective, predictive, prognostic molecular biomarkers for OC is an urgent need. Objective: The study intended to explore the potential tumorigenesis mechanisms to identify promising biomarkers and improve survival in OC patients. Design: The research team performed a genetic analysis. Setting: The study took place at First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China. Outcome Measures: The research team: (1) obtained GSE66957 and GSE81778 gene expression profiles from the Gene Expression Omnibus (GEO) database and identified 468 differentially expressed genes (DEGs); (2) conducted functional enrichment analysis and constructed a protein-to-protein interaction (PPI) network; (3) identified the OC survival-related genes using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) webserver and compared those genes with upregulated DEGs to identify the core genes; (4) used GEPIA2 and the Kaplan-Meier plotter to explore the expression profiles and the prognostic values of the core genes in OC; (5) used the LinkOmics, Oncomine, and GEPIA2 web servers to perform co-expression analysis and explore functional networks correlated with keratin 7 (KRT7); (6) performed correlation analyses between KRT7, the six main types of tumor-infiltrating lymphocytes (TILs), and immune signatures, using the TIMER tool; and (7) subsequently detected the KRT7 expression in the cell lines IOSE80, A2780, A2780/PTX, ho8910, skov3, and ovcar3 using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) technology. Results: High expression levels of KRT7 were significantly correlated with progression-free survival (PFS) and poor overall survival (OS) for OC patients, with logrank P = .0074 and logrank P = .014, respectively. The expression levels of KRT7 were also significantly correlated with the infiltrated neutrophil levels (r = 0.169, P = .0077). The study identified neutrophils as potential predictors of survival in OC. Moreover, the expression levels of KRT7 in OC were positively correlated with 51 (31.68%) of the 161 immune gene markers. The RT-qPCR analyses revealed a high expression of KRT7 in the paclitaxel-resistant OC cell line. Conclusions: KRT7 is correlated with immune infiltration and paclitaxel resistance in OC patients. Therefore, clinicians could use KRT7 as a prognostic marker and a target in the development of new drugs.

Construction and validation of a risk scoring model for diffuse large B-cell lymphoma based on ferroptosis-related genes and its association with immune infiltration.

BACKGROUNDS: The prognostic significance of ferroptosis-related genes is well known. However, survival- and ferroptosis-related genes are not currently considered in risk scoring models for diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: Ferroptosis regulators and markers were downloaded from the FerrDb database. The transcriptome profiling data were collected from the cancer genome atlas (TCGA). Transcriptome data and corresponding clinical information of DLBCL were downloaded from the gene expression omnibus (GEO). The validation data were downloaded using the UCSC Xena browser. ConsensusClusterPlus was used to categorize DLBCL samples according to gene expression profiles. The survival function was plotted with the Kaplan-Meier plots. The nomogram was built using multivariate logistic regression analysis and the Cox proportional hazards regression model. RESULTS: Based on the GSE11318 dataset of 203 samples and 267 ferroptosis-related gene expression profiles, we identified four clusters. A total of 19 survival-related genes were found associated with ferroptosis. The prognostic risk scoring model was constructed based on the regression coefficients. The obtained area under the receiver operating characteristic curve (AUC) values were 0.769, 0.801, and 0.791 for 1-, 3-, and 5-year survival, respectively. DLBCL samples with cluster 2 or cancer stage IV have shorter survival. Correlations between the immune infiltration and risk scores of the 12 immune cells were demonstrated. The response of DLBCL to doxorubicin was effectively validated by the risk scoring model. CONCLUSIONS: In this study, a ferroptosis-based risk scoring model for patients with DLBCL was constructed and validated in an independent dataset. This risk score model has a better efficacy in predicting survival compared to clinical characteristics.

MicroRNA-374c-5p regulates the invasion and migration of cervical cancer by acting on the Foxc1/snail pathway.

Some microRNAs (miRNAs) have been implicated in cervical cancer development and progression. However, the roles and mechanisms of several miRNAs in epithelial-mesenchymal transition (EMT) in cervical cancer remain poorly understood. Here, we conducted a microarray analysis and found that miR-374c-5p was most down-regulated miRNA in TGFß1-treated cervical cancer cells compared to the expression in parental cell lines. Ectopic overexpression of miR-374c-5p inhibited cervical cancerl invasion and migration in TGFß1- treated cervical cancer cells. Conversely, miR-374c-5p knockdown increased the migration and invasion abilities of parental cell lines. Moreover, miR-374c-5p exerted its function by directly targeting the FOXC1 3/-UTR and repressing FOXC1 expression, thus leading to suppression of snail. In clinical cervical cancer samples, lower miR-374c-5p expression predicted poor patient survival and highe lymph node metastasis in cervical cancers. miR-374c-5p was negatively correlated with FOXC1, which was upregulated in cervical cancers with lymph node metastasis. Taken together, our findings highlight the important role of miR-374c-5p in regulating cervical cancers metastasis by targeting FOXC1, suggesting that miR-374c-5p may represent a novel potential therapeutic target and prognostic marker in cervical cancers.