Wei Cui

Evaluation of the SureX HPV genotyping test for the detection of high-risk HPV in cervical cancer screening

Abstract Background The SureX HPV genotyping test (SureX HPV test), which targets the human papillomavirus (HPV) E6/E7 genes was compared with the Cobas 4800 and Venus HPV tests for detecting 14 high-risk HPV (HR-HPV) types in clinical referral and follow-up patients to evaluate its value for cervical cancer screening. Methods Two different populations were enrolled in the study. The first population comprised 185 cases and was used for comparing the SureX HPV test (Health, China) with the Cobas 4800 test (Roche, USA). The second population comprised 290 cases and was used for comparing the SureX HPV test (Health, China) with the Venus HPV test (Zhijiang, China). Polymerase chain reaction (PCR) sequencing was performed for further confirmation of discordant results. Results In the first population, the overall agreement rate was 95.6% for 14 high-risk HPV types. Eight discordant cases were confirmed by PCR sequencing, which showed that the agreement rates were 75.0% between the SureX HPV test and PCR sequencing and 25.0% between the Cobas 4800 test and PCR sequencing ( P  < 0.01). In the second population, the overall agreement rate was 95.5%. Thirteen discordant cases were confirmed by PCR sequencing, which showed that the agreement rates were 76.9% between the SureX HPV test and PCR sequencing and 23.1% between the Venus HPV test and PCR sequencing ( P  < 0.01). With cervical intraepithelial neoplasia grade 2+ (CIN2+) as the reference standard, the sensitivity values of the SureX HPV test and the Venus HPV test were 93.5% and 92.0%, ( P  > 0.05), while the specificity values were 43.3% and 46.7%, respectively ( P  > 0.05). Conclusion The SureX HPV test had good consistency with both the Cobas 4800 and Venus HPV tests for 14 HR-HPV types. In addition, it avoided some false negatives and false positives. Therefore, the SureX HPV test can be used for cervical cancer screening.

ALKBH5-mediated m6A regulates the alternative splicing events of SRSF10 in ovarian cancer

N6-methyladenosine (m6A) methylation was found to be involved in the tumorigenesis and development of ovarian cancer. Until now, it is not clear to identify the mechanism by m6A demethylase ALKBH5 affects RNA splicing in ovarian cancer. In this study, we examined ALKBH5 protein expression and m6A levels by immunohistochemistry and analyzed their correlation with clinical features and prognosis in patients with ovarian cancer. We identified the elevated expression of ALKBH5 and a general reduction in the level of m6A in ovarian cancer patients. In the ovarian cancer cell line A2780, ALKBH5 depletion was found using the siRNA strategy or the CRISPR/Cas9 knockout (KO) method, which significantly reduced the level of m6A and inhibited cell viability, proliferation, and migration. The MeRIP-seq and RNA-seq showed that ALKBH5-regulated m6A RNA modification mainly affects RNA splicing function in ovarian cancer cells. SRSF10 is a key target gene involved in alternative splicing regulation through ALKBH5-m6A. ALKBH5 knockdown resulted in increased retention of SRSF10 exon 5 and decreased expression of transcript SRSF10-211. In conclusion, the alternative splicing regulation effect by ALKBH5-mediated m6A suggests a novel promising approach for m6A modification in OC and provides novel insights into the mechanisms involved in ovarian cancer therapy.