Identification of Ferroptosis-Related Gene Prognostic Signature and HSF1 for Reversing Doxorubicin and Gemcitabine Resistance in Uterine Carcinosarcoma.

PURPOSE: Iron metabolism and ferroptosis play crucial roles in the pathogenesis of cancer. In this study, we aim to study the role of ferroptosis-related genes (FRGs) in uterine carcinosarcoma (UCS) and identify potential target for UCS. METHODS: Prognostic differentially expressed FRGs were identified of in the TCGA cohort. Integrated analysis, cox regression, and the least absolute shrinkage and selection operator (LASSO) methods of FRGs were performed to construct a multigene signature prognostic model. Moreover, a dataset from Gene Expression Omnibus (GEO) served as an external validation. HSF1 was knockdown in MES-SA and FU-MMT-1 cells, and cell viability, lipid ROS, and intracellular iron level were detected when combined with doxorubicin or gemcitabine. RESULT: Five FRGs were selected to construct a prognostic model of UCS. The group with high-risk signature score exhibited obviously lower overall survival (OS) than the group with low risk signature score in both TCGA and validated GEO cohorts. Multivariate Cox regression analysis further indicated that the risk score was an independent factor for the prognosis of UCS patients. The high-risk group of UCS has a higher sensitivity in the treatment of doxorubicin and gemcitabine. Knocking down of HSF1 in MES-SA and FU-MMT-1 cells was more sensitive to doxorubicin and gemcitabine via increasing ferroptosis. CONCLUSIONS: The five FRGs risk signature prognostic model having a superior and drug sensitivity predictive performance for OS in UCS, and HSF1 is a potential marker sensitive to doxorubicin and gemcitabine in UCS patients.

A Novel Circulating MiRNA-Based Signature for the Diagnosis and Prognosis Prediction of Early-Stage Cervical Cancer.

BACKGROUND: MicroRNAs (miRNAs) have been shown to play a key role in regulating the progression of cervical cancer (CC). This study aimed to develop a circulating miRNA-based molecular signature for the diagnosis and prognosis prediction of early-stage CC. METHODS: This study included 112 patients diagnosed with early-stage CC, 45 patients confirmed with cervical intraepithelial neoplasia (CIN) and 90 healthy subjects. Compared to the normal controls, the expression level of miR-21 was increased, while the levels of miR-125b and miR-370 were decreased in CC in both GSE30656 and The Cancer Genome Atlas (TCGA) cohort. The expression levels and diagnostic value of these candidate miRNAs were then validated through qRT-PCR. Their diagnostic and prognostic values for early-stage CC were further explored. RESULTS: Compared to the patients with CIN and healthy subjects, serum miR-21 was increased, while serum miR-125b and serum miR-370 were reduced in early-stage CC. In addition, combining these molecules yielded good performance for differentiating early-stage CC from CIN or healthy subjects. Moreover, strong association was found between serum miR-21 and lymph node metastasis (LNM) as well as recurrence-free survival of early-stage CC. Similar observations were found for serum miR-125b and serum miR-370. Patients with simultaneously high serum miR-21 + low serum miR-125b + low serum miR-370 suffered a high risk of LNM and recurrence, while those with low serum miR-21 + high serum miR-125b + high serum miR-370 had little risk for LNM and recurrence. CONCLUSIONS: Combining serum miR-21, miR-125b and miR-370 as a miRNA-based signature is promising for the detection and prognosis prediction of early-stage CC.