Identification of immunity- and ferroptosis-related genes for predicting the prognosis of serous ovarian cancer

Abstract

BackgroundSerous ovarian cancer (SOC) is the most common type of ovarian cancer (OC), with bad outcomes. To improve the prognosis of SOC patients, a novel risk signature was developed by combining immunity- and ferroptosis-related genes. MethodsBy means of comparing SOC tissues with normal tissues, we screened the differential expression of immunity-related genes (DE-IRGs) and ferroptosis-related genes(DE-FRGs) with the standards of |log2fold change| > 1 and false discovery rate (FDR) < 0.05. After obtaining the meaningful differentially expressed genes from immune and ferroptosis (DEGs), we established a prognostic risk signature by utilizing Cox regression analyses in TCGA training set, which was validated in TCGA testing set and GSE26712 dataset. Besides, the differential expression of immune-related markers, immunophenoscore (IPS), TIDE score,T cell dysfunction score and T cell exclusion score were also analyzed. We further verified the expression of target genes in ovarian tumor cells lines by QRT-PCR. ResultsA risk signature constructed by totally four immunity- and ferroptosis-related DEGs (CXCL11, CX3CR1, FH, and DNAJB6) was developed, which distinguished the SOC patients as high-risk and low-risk groups. Patients in the high-risk group showed a lower overall survival (OS) than those in the low-risk group. Furthermore, the risk score was independent when analyzed with clinical augments, which was significantly associated with 13 KEGG signaling pathways. The gene signature showed favorable predictive performance according to Receiver operating characteristic (ROC) curves. Notably, the expression of immune-related markers or IPS indicated a negative connection with the risk score. SOC patients had a lower score of TIDE and T cell dysfunction than Whom had a higher score. Nonetheless, there were no significant differences in T cell exclusion scores between the two groups.Compared with normal ovarian cell line IOSE-80,QRT-PCR experiments exhibited that CXCL11, CX3CR1and FH were up-regulated in ovarian tumor cells lines(SK-OV-3,COC1,A2780),while DNAJB6 was down-regulated. ConclusionFour-biomarker signature formed by immunity- and ferroptosis-related genes may be clinically used as risk stratifcation tool in serous ovarian cancer,which can help further clinical decision-making regarding prognostic prediction,individualized treatment and follow-up scheduling.