Hong Wang

The landscape and prognostic value of immune characteristics in uterine corpus endometrial cancer

Abstract In the present study, we explored the clinical and immunological characteristics of 575 uterine corpus endometrial carcinoma (UCEC) samples obtained from The Cancer Genome Atlas (TCGA) using the ESTIMATE and CIBERSORT algorithms. First, Kaplan–Meier and univariate Cox regression analyses indicated that the immune cell score was a prognostic factor for overall survival (OS) and recurrence-free survival (RFS). Multivariate Cox regression analysis further revealed that the immune cell score was an independent prognostic factor for UCEC patients. Second, we investigated the correlation between the infiltration levels of 22 types of immune cells and the immune score. Survival analysis based on the 22 immune cell types showed that higher levels of regulatory T cell, activated NK cell, and follicular helper T-cell infiltration were associated with longer OS, while higher levels of CD8+ T cell and naive B-cell infiltration were associated with longer RFS. Next, we performed differential expression and prognosis analyses on 1534 immune-related genes and selected five from 14 candidate genes to construct a prognostic prediction model. The area under the receiver-operating characteristic (ROC) curve (AUC) for 3- and 5-year survival were 0.711 and 0.728, respectively. Further validation using a stage I–II subgroup showed similar results, presenting AUC values for 3- and five-year survival of 0.677 and 0.692, respectively. Taken together, the present study provides not only a deeper understanding of the relationship between UCEC and the immune landscape but also guidance for the future development of UCEC immunotherapy.

HPV testing with 16/18 genotyping for risk stratification among women with normal cytology: a multicenter prospective cohort study from China

ABSTRACT To evaluate the clinical performance of Hybribio’s 14-type HPV real-time PCR with 16/18 genotyping (HBRT-H14) and its risk stratification utility among women with normal cytology (NILM). From 2017 to 2020, a multicenter cohort enrolled 8,401 women aged 30–64 years with NILM cytology. Baseline HPV testing used HBRT-H14. Women positive for HPV 16/18 were referred for colposcopy; follow-up was annual for 3 years or until the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Analyses included 6,679 women who completed follow-up. Overall HPV positivity was 11.4%, including 2.3% HPV 16/18. Over 3 years, sensitivity and specificity of HPV positivity for CIN2+ were 92.3% (95% confidence interval [CI]: 84.2–96.4) and 89.6% (88.8–90.3). For HPV 16/18 positivity, sensitivity and specificity were 41.0% (30.8–52.1) and 98.2% (97.8–98.5). Three-year cumulative CIN2+ risk was 20.9% (15.2–28.1) for HPV 16/18-positive women, 6.6% (4.9–8.9) for other types, and 0.1% (0.04–0.2) for HPV-negative women. HBRT-H14 shows strong clinical performance for detecting CIN2+, and HPV 16/18 genotyping provides effective risk stratification among women with NILM cytology. Findings support integration of HBRT-H14 into HPV-based screening pathways with HPV 16/18 genotyping and cytology triage of other types. IMPORTANCE This multicenter prospective study evaluated the Hybribio 14 high-risk HPV real-time PCR assay (HBRT-H14) in 8,401 women with normal (NILM) cytology under guideline-based follow-up. The assay showed high clinical sensitivity and a very low risk among HPV-negative women, and HPV 16/18 genotyping provided clear risk stratification. These findings deliver large-scale, practice-oriented evidence supporting integration of HBRT-H14 into HPV-based screening pathways that use HPV 16/18 genotyping with cytology triage of other types.

Hsa_circ_0001741 Suppresses Ovarian Cancer Cell Proliferations Through Adsorption of miR-188-5p and Promotion of FOXN2 Expression

Ovarian cancer (OC) is among several general malignant gynecological cancers associated with high mortality rates on a global scale. Earlier investigations have revealed a critical role of circular RNAs (circRNAs) in OC development, which is a new class of endogenous non-coding RNA (ncRNA) that reported to mediate progression of diverse tumor types. At present, the precise involvement of circRNAs and associated regulatory mechanisms in OC remain unknown. In this study, hsa_circ_0001741 expression patterns in OC cells and tissues were tested. The underlying regulatory pathways and targets were further explored with the aid of bioinformatics, luciferase reporter, 5-ethynyl-2'-deoxyuridine (EdU) and cell counting kit-8 (CCK-8) analyses. Further investigation of the hsa_circ_0001741 effects on tumor growth in vivo revealed abnormal circRNA expression in OC. hsa_circ_0001741 expression reduced in OC cells and tissues, indicative of activity in OC progression. hsa_circ_0001741 upregulation resulted in OC proliferation inhibitions. The luciferase reporter outputs verified miR-188-5p and FOXN2 as hsa_circ_0001741 downstream targets. FOXN2 silencing or miR-188-5p upregulations reversed inhibitory effects regarding hsa_circ_0001741 on OC cell proliferation. Therefore our data suggested that hsa_circ_0001741 upregulation inhibited proliferation of OC through modulatory effects on miR-188-5p/FOXN2 signaling.

MiR-101-3p Suppresses Progression of Cervical Squamous Cell Carcinoma by Targeting and Down-Regulating KPNA2

Objective We explored mechanism of microRNA-101-3p/Karyopherin α2 (KPNA2) axis in cervical squamous cell carcinoma. Methods: Bioinformatics methods were applied to identify genes for the study. Cell functional assays were implemented to examine the role of the genes in malignant progression of cervical squamous cell carcinoma. Targeting relationship between genes was verified by dual-luciferase assay. Results: MicroRNA-101-3p was lowly expressed in cervical squamous cell carcinoma, while KPNA2 was highly expressed. Dual-luciferase assay identified direct targeting relationship between microRNA-101-3p and KPNA2. Functional assays manifested that highly expressed microRNA-101-3p suppressed cervical squamous cell carcinoma cell growth by targeting KPNA2. Conclusion: Overall, microRNA-101-3p/KPNA2 axis can play an important part in progression of cervical squamous cell carcinoma.