Jiawen Zhang

Clinicopathological and immunological characterization of RNA m6A methylation regulators in ovarian cancer

AbstractBackgroundN6‐methyladenosine (m6A) modification is one of the critical gene regulatory mechanisms implicated in cancer biology. However, the roles of m6A regulators in ovarian cancer are still poorly understood.MethodsWe integrated multiple databases including Gene Expression Omnibus (GEO), ROC Plotter, Kaplan‐Meier Plotter, and Tumor Immune Estimation Resource (TIMER) to explore clinicopathological significance of m6A regulators in ovarian cancer.ResultsWe showed that alterations in the expression of m6A regulators were related to the malignancy and poor prognosis of ovarian cancer. We found decreased YTHDC1 and increased RBM15 expressions were associated with ovarian cancer cell metastases and HNRNPC was a predictor of paclitaxel resistance. Moreover, dysregulated m6A regulators were enriched in the activation of cancer‐related pathways. Our results further demonstrated that the level of immune cell infiltration and the expression of various immune gene markers were closely associated with the expressions of specific m6A regulators (RBM15B, ZC3H13, YTHDF1, and IGF2BP1).ConclusionsOur study establishes a new prognostic profile of ovarian cancer patients based on m6A regulators, and highlights the potential roles of m6A regulators in ovarian cancer development.

Clinical implication and immunological characterisation of the ARF-GEF family member CYTH4 in ovarian cancer

The GTP exchange factors on ADP-ribosylation factor (ARF) mediate the GDP/GTP exchange on ARF, serve as regulators in protein trafficking and membrane dynamics, and play critical roles in various cell processes. However, the relationship between the expression of ARF-GEF family genes and clinical implications in ovarian cancer remains unclear. We performed a systematic investigation on the role of ARF-GEF family genes in ovarian cancer by using Gene Expression Omnibus (GEO), Kaplan-Meier plotter, Gene set enrichment analysis (GSEA), TIMER and TISIDB database. We found that the ARF-GEF family gene CYTH4 exhibited significant expressional upregulation in ovarian cancer compared to normal ovary tissues. The expression of CYTH4 was also higher in metastases from the omentum than in matched primary ovarian tumours. Kaplan-Meier plotter showed that high expression of CYTH4 predicted worse overall survival, progression free survival and post-progression survival of ovarian cancer patients. Notably, from our correlation analysis, CYTH4 expression showed closely association with tumour-infiltrating immune cells. Intriguingly, the expression of CYTH4 was also significantly correlated with a variety of immunomodulators, chemokines and major histocompatibility complex molecules. Overall, our findings provide a valuable source of data about the clinical significance of CYTH4 in ovarian cancer.

The distribution and pathogenic risk of non‐9‐valent vaccine covered HPV subtypes in cervical lesions

AbstractHuman papillomavirus (HPV) infection is the main cause of female precancerous lesions and cervical cancer. The development and application of HPV prophylactic vaccines have been recognized as a major effective intervention for the control of cervical lesions. However, the infection rate and clinical characters of non‐9‐valent vaccine covered HPV subtypes are still worth studying. In this retrospective study, we included patients diagnosed and treated in the Department of Gynecology of Shanghai General Hospital between January 2017 and February 2021. The clinical features of non‐9‐valent vaccine covered HPV subtypes were explored in 2179 patients who have normal results, 338 patients with cervical intraepithelial neoplasia 1 (CIN1), and 153 patients with ≥CIN2. Univariate analysis showed that compared to the normal cervix group, age ≥50, pregnancy ≥5, delivery ≥3, menopause, no condom use, and cervical transformation zone type III were risk factors for CIN1 or ≥CIN2 (p < 0.05). Thirty‐one percent of CIN1 and 26% of ≥CIN2 were attributed to HPV51, HPV53, HPV56, and HPV68. Multivariate analysis revealed that HPV53, HPV81, age, menopause, cervical transformation area and involved glands were independent risk factors for ≥CIN2 group compared to the CIN1 group (p < 0.05). Additionally, among the 14 non‐9‐valent vaccine covered HPV subtypes, the infection rates of HPV53, 56, 51, and 68 were higher in this study. In conclusion, our study demonstrated the distribution and pathogenic risk of non‐9‐valent vaccine covered HPV subtypes in cervical lesions. These findings might supply a foundation for optimizing cervical cancer prevention in the post‐vaccine era.