Lulu Yu

Surgical Management of Fibroids: A Changing Landscape

Background: Uterine fibroids affect patients’ quality of life and contribute significantly to health care costs. Studies from 2009 to 2011 demonstrated that fibroids disproportionately affect Black women, with lower odds of uterine preservation and minimally invasive approaches. Objective: This is a retrospective cohort study of data abstracted from the National Surgical Quality Improvement Program database from 2015 to 2019 examining trends in surgical management of uterine fibroids and exploring disparities in surgical approach in a modern cohort. Results: In total, 52,909 women underwent hysterectomy and 15,485 women underwent myomectomy between 2015 and 2019. Over the study period, the overall number of surgeries for fibroids increased by 44.2% with minimally invasive hysterectomy responsible for the majority of this increase. The proportion of patients who underwent myomectomy significantly increased (20.85% to 24.62%, p value <0.0001), whereas hysterectomy significantly decreased (79.15% to 75.38%, p value <0.0001). Bivariate analysis identified younger age, non-White race, and body mass index (BMI) <25 as significantly associated with performance of myomectomy. Non-Hispanic Black (adjusted odds ratio [aOR]: 3.55, 95% confidence interval [CI]: 3.23–3.89), Asian (aOR: 3.26, 95% CI: 2.80–3.80), and Hispanic Black (aOR: 5.50, 95% CI: 3.29–9.25) women were more likely to undergo myomectomy than non-Hispanic White women. Conclusion: Surgical treatment for fibroids increased over time, shifting toward uterine preservation. Myomectomy performance is associated with lower age and BMI and identifying as a racial and/or ethnic minority. These trends may represent improved access to surgical treatment of fibroids, resulting from the growth of minimally invasive gynecological surgery as a specialty and advocacy for equitable health care for all patients.

The long noncoding RNA lnc-FANCI-2 intrinsically restricts RAS signaling in human papillomavirus type 16-infected cervical cancer cells

Increased expression of lnc-FANCI-2, a newly discovered long noncoding RNA, is associated with cervical lesion progression from cervical intraepithelial neoplasia stage 1 (CIN1, low grade), CIN2–3 (high grade), to cervical cancer. Viral oncoprotein E7 of high-risk human papillomaviruses (HR-HPVs) and host transcription factor YY1 are two major factors promoting lnc-FANCI-2 expression. Using CRISPR-Cas9 technology, we knocked out the expression of lnc-FANCI-2 in the HPV16-positive cervical cancer cell line, CaSki cells. The selected knockout (KO) single-cell clones displayed altered cell morphology and proliferation with changes of cellular soluble receptors, but normal HPV16 E6 and E7 expression. Relative to the parental cells, lnc-FANCI-2 KO cells exhibited significantly increased RAS signaling and epithelial-mesenchymal transition, but decreased response to IFN signaling, along with increased p-Akt and p-Erk1/2 (two RAS signaling effectors), IGFBP3, MCAM, VIM, and CCND2 (cyclin D2) and decreased expression of RAC3. lnc-FANCI-2 in CaSki interacts with cellular proteins H13, HNRH1, K1H1, MAP4K4, and RNPS1. MAP4K4 knockdown led to enhance the expression of p-Erk1/2 and p-Akt. High lnc-FANCI-2 and low MCAM levels in cervical cancer tissues were found to be associated with patients’ survival. A key function of lnc-FANCI-2 intrinsically regulates RAS signaling to impact cervical lesion progression and cervical cancer prognosis.