Shan Kang

UBE2J1 is identified as a novel plasma cell-related gene involved in the prognosis of high-grade serous ovarian cancer

Immune cells within tumor tissues play important roles in remodeling the tumor microenvironment, thus affecting tumor progression and the therapeutic response. The current study was designed to identify key markers of plasma cells and explore their role in high-grade serous ovarian cancer (HGSOC). We utilized single-cell sequencing data from the Gene Expression Omnibus (GEO) database to identify key immune cell types within HGSOC tissues and to extract related markers via the Seurat package. The effects of immune cell markers on prognosis were analyzed via univariate Cox regression, least absolute shrinkage and selection operator (LASSO) and gene set variation analysis (GSVA) of bulk sequencing data from The Cancer Genome Atlas (TCGA)-HGSOC cohort. Finally, the effects of key markers on HGSOC cells were evaluated via Cell Counting Kit-8 (CCK-8), Transwell, colony formation, wound healing, immunofluorescence and in vivo tumor growth assays. At the single-cell level, we detected a significant increase in the proportion of plasma cells in HGSOC samples compared to that in normal ovarian samples. Within HGSOC tissues, these plasma cells were found to interact with CD8 + T cells, fibroblasts and endothelial cells. In addition, patients in the high-plasma cell-related score group had better survival rates and higher epithelial‒mesenchymal transition (EMT), apoptosis and immune scores. Moreover, univariate Cox and LASSO regression analyses revealed that ubiquitin-conjugating enzyme E2 J1 (UBE2J1) is a prognostic marker in HGSOC. Further functional studies revealed that overexpression of UBE2J1 promoted cell proliferation, invasion, migration and colony formation, whereas UBE2J1 knockdown attenuated the abovementioned cellular behaviors. Additionally, UBE2J1 overexpression promoted EMT, as evidenced by alterations in the protein expression levels of N-cadherin, snail family transcriptional repressor 2 (Slug), Twist family BHLH transcription factor 1 (Twist 1) and E-cadherin. Moreover, we found that UBE2J1 silencing was able to inhibit the tumor growth in vivo. Overall, this study elucidated the role of plasma cells and revealed UBE2J1 as a novel oncogene in HGSOC, uncovering new mechanisms related to HGSOC tumorigenesis and promising therapeutic targets for HGSOC patients.

A functional polymorphism in the poly(ADP-ribose) polymerase-1 gene is associated with platinum-based chemotherapeutic response and prognosis in epithelial ovarian cancer patients

To explore the effects of two functional genetic variants of poly(ADP-ribose) polymerase-1 (PARP-1) on the susceptibility to epithelial ovarian cancer (EOC), the platinum-based chemotherapeutic response, and the prognosis of northern Chinese patients. This case-control study included 710 EOC patients in the case group and 700 healthy women in the control group. Two polymorphisms (rs1136410 and rs8679) of PARP-1 were genotyped by polymerase chain reaction and ligase detection reaction. The genotype frequencies of rs1136410 and rs8679 were not significantly different between the case and control groups. However, the CC genotype of rs1136410 was significantly associated with a favorable response to platinum drugs. Compared with the TT genotype, the CC genotype of rs1136410 was related to a reduced risk of platinum resistance (adjusted OR: 0.40; 95% CI = 0.24-0.67; P = 0.001). In addition, multivariable analysis containing clinical variables showed that patients who carried the rs1136410 CC genotype had a significantly improved progression-free survival compared with patients who carried the TT genotype (HR = 0.67, 95% CI = 0.47-0.97, P = 0.031). The rs1136410 polymorphism may serve as a potential marker for predicting the response to platinum agents and prognosis of EOC patients treated with surgery and platinum-based chemotherapy.

Hypermethylation of the GRHL2 promoter region is associated with ovarian endometriosis

Abstract Abnormal gene expression caused by epigenetic changes, including DNA methylation, is associated with the development and progression of endometriosis. Grainyhead-like 2 gene (GRHL2), a suppressor of epithelial–mesenchymal transition, has been suggested to be associated with the occurrence, progression and poor survival of a variety of cancers. Although endometriosis is a benign disease, it has the biological behaviour of migration and invasion as malignant tumor. This study aims to determine whether the abnormal expression of the GRHL2 caused by aberrant methylation of its promoter is associated with the pathogenesis of ovarian endometriosis. Our results demonstrated that GRHL2 promoter region was significantly hypermethylated in the ectopic endometrium of patients with ovarian endometriosis compared with the normal endometrium of control patients. In contrast, the levels of GRHL2 mRNA and protein were significantly lower in the ectopic endometrium than in the control endometrium. Correlation analysis showed the methylation levels of GRHL2 were significantly negatively correlated with the mRNA expression of GRHL2. Moreover, the in vitro results suggested that the knockdown of GRHL2 could significantly increase the invasion and migration ability of EECs and may promote ZEB1 and vimentin expression while decreasing the expression of E-cadherin in EECs. Taken together, these results suggest that the low expression of GRHL2 caused by hypermethylation of the GRHL2 promoter is associated with ovarian endometriosis. The knockdown of GRHL2 may be involved in the occurrence of endometriosis by increasing EEC migration and invasion. This study provides more evidence for the hypothesis that endometriosis may be an epigenetic regulatory disorder.

Risk factors for and delayed recognition of genitourinary fistula following radical hysterectomy for cervical cancer: a population-based analysis

This study aimed to identify the risk factors for genitourinary fistulas and delayed fistula recognition after radical hysterectomy for cervical cancer. This study was a retrospective analysis of data collected in the Major Surgical complications of Cervical Cancer in China (MSCCCC) database from 2004-2016. Data on sociodemographic characteristics, clinical characteristics, and hospital characteristics were extracted. Differences in the odds of genitourinary fistula development were investigated with multivariate logistic regression analyses, and differences in the time to recognition of genitourinary fistula were assessed by Kruskal-Wallis test. In this study, 23,404 patients met the inclusion criteria. Surgery in a cancer center, a women's and children's hospital, a facility in a first-tier city, or southwest region, stage IIA, type C1 hysterectomy, laparoscopic surgery and ureteral injury were associated with a higher risk of ureterovaginal fistula (UVF) (p<0.050). Surgery in southwest region, bladder injury and laparoscopic surgery were associated with greater odds of vesicovaginal fistula (VVF) (p<0.050). Surgery at cancer centers and high-volume hospitals was associated with an increase in the median time to UVF recognition (p=0.016; p=0.005). International Federation of Gynecology and Obstetrics (FIGO) stage IIA1-IIB was associated with delayed recognition of VVF (p=0.040). Intraoperative urinary tract injury and surgical approach were associated with differences in the development of UVFs and VVFs. Patients who underwent surgery in cancer centers and high-volume hospitals were more likely to experience delayed recognition of UVF. Patients with FIGO stage IIA1-IIB disease were more likely to experience delayed recognition of VVF.