Xifeng Xiong

Prognostic Significance of the CXCLs and Its Impact on the Immune Microenvironment in Ovarian Cancer

The chemokine (C-X-C motif) ligand (CXCL) family in tumor tissue is closely related to tumor growth, metastasis, and survival. However, the differential expression profile and prognostic value of the CXCLs in ovarian cancer (OC) have not been elucidated. Therefore, we studied the expression levels and mutations of CXCLs in OC patient in TCGA and various public databases. The expression differences of CXCLs in OC cancer tissues and normal tissues were compared through the Gene Expression Profiling Interactive Analysis (GEPIA) database. The effect of CXCLs on OC prognosis was analyzed using the Kaplan-Meier curves in GEPIA database. The impact of CXCLs on immune infiltration and clinicopathological outcomes in OC was assessed using the TIMER algorithm. Compared with normal tissues, we found that eight CXCLs were significantly differentially expressed in OC. The expression levels of CXCL9 ( P = 0.0201 ), CXCL11 ( P = 0.0385 ), and CXCL13 ( P = 0.0288 ) were significantly associated with tumor stage. CXCL13 was the only gene that significantly affected both disease-free survival (DFS) and overall survival (OS) in OC, and higher CXCL13 transcript levels implied longer DFS and OS. Although there was no significant impact on DFS, CXCL10 ( P = 0.0079 ) and CXCL11 ( P = 0.0011 ) expression levels had a significant effect on OS in OC. At the same time, CXCLs were significantly associated with several immune-infiltrating cells in OC tissues. The CXCLs were significantly associated with one or more immune-infiltrating cells in OC tissue. CXCL13 was differentially expressed in OC and significantly affected the prognosis of patients and was a potential marker of OC prognosis.

FBP1 knockdown decreases ovarian cancer formation and cisplatin resistance through EZH2-mediated H3K27me3

Abstract Worldwide, ovarian cancer (OC) is the seventh common cancer and the second most common cause of cancer death in women. Due to high rates of relapse, there is an urgent need for the identification of new targets for OC treatment. The far-upstream element binding protein 1 (FBP1) and enhancer of zeste homolog 2 (EZH2) are emerging proto-oncogenes that regulate cell proliferation and metastasis. In the present study, Oncomine data analysis demonstrated that FBP1 was closely associated with the development of OC, and The Cancer Genome Atlas (TCGA) data analysis indicated that there was a positive correlation between FBP1 and EZH2 in ovarian tissues. Moreover, we found that FBP1 knockdown suppressed tumor formation in nude mice and cisplatin resistance of OC cells, but the role of FBP1 in the cisplatin resistance of OC cells remained unclear. In addition, we verified physical binding between FBP1 and EZH2 in OC cells, and we demonstrated that FBP1 knockdown enhanced cisplatin cytotoxicity in OC cells and down-regulated EZH2 expression and trimethylation of H3K27. These results suggested that FBP1 increases cisplatin resistance of OC cells by up-regulating EZH2/H3K27me3. Thus, FBP1 is a prospective novel target for the development of OC treatment.