Lei Zhang

Genetic Causal Relationship Between Systemic Lupus Erythematosus and Malignant Tumors of the Female Reproductive System: A GWAS Analysis in European Populations

Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that primarily affects women of reproductive age. Existing studies have demonstrated complex associations between SLE and various diseases, but its genetic relationship with malignant tumors of the female reproductive system has not been fully elucidated. This study is aimed at exploring the potential genetic associations and shared molecular basis between SLE and female reproductive system malignancies using genome‐wide association studies (GWASs) and cross‐trait analysis.Methods: We selected genetic variants significantly associated with SLE (p < 5 × 10−8) from large‐scale GWAS databases as genetic instruments and applied various statistical methods to analyze the associations between SLE and cervical cancer, endometrial cancer, ovarian cancer, vulvar cancer, vaginal cancer, and uterine cancer. The primary analysis was conducted using inverse variance weighting (IVW), supplemented by Egger regression, weighted median, and weighted mode methods. To control for potential confounders, we performed multivariable analysis while including BMI, estradiol, and CRP as covariates. Additionally, cross‐trait analysis using the association analysis based on subset (ASSET) method was employed to identify shared genetic variants and their effect directions between SLE and uterine cancer.Results: Genetic association analysis showed a significant negative association between SLE and endometrial cancer (OR = 0.972, 95% CI [0.946–0.998], p = 0.038), suggesting that SLE may be associated with a reduced risk of endometrial cancer. For uterine cancer, the weighted median method also indicated a marginally significant negative association (OR = 0.955, 95% CI [0.912–1.000], p = 0.049). Multivariable analysis further confirmed that the protective association between SLE and endometrial cancer remained significant after controlling for BMI, estradiol, and CRP (OR = 0.96, 95% CI [0.93–0.99], p = 0.014). However, no significant association was observed between SLE and cervical cancer, ovarian cancer, vulvar cancer, or vaginal cancer. Cross‐trait analysis identified 193 shared genetic variants between SLE and endometrial cancer and 71 shared variants between SLE and uterine cancer, with rs2442719 and rs3131004 showing consistent effect directions in both comparisons.Conclusion: This study provides genetic epidemiological evidence suggesting that SLE may have a protective effect against endometrial and uterine cancers and identifies potential shared genetic bases. These findings offer new insights into the relationship between SLE and gynecological tumors and may provide references for the prevention and treatment of related diseases.

HPV vaccination is highly effective and cost‐effective for cervical cancer prevention in women living with HIV in China: A cost‐effectiveness analysis

AbstractThe presence of human immunodeficiency virus (HIV) infection increases the risk of acquiring human papillomavirus (HPV) infection and developing HPV‐related adversities. We aimed to estimate the cost‐effectiveness of HPV vaccination for women living with HIV in a Chinese setting. A decision‐analysis Markov model was developed to estimate the cost‐effectiveness of 36 HPV vaccination strategies for women living with HIV aged 18–45 years, from the healthcare system perspective. With the status quo, not vaccinating women living with HIV would lead to 51.99% (51,985/100,000) HIV‐related deaths; 35.10% (35,098/100,000) would develop genital warts, 0.36% (355/100,000) develop cervical cancer, and among which 63.66% (226/355) die from cervical cancer over their lifetime (1,601,457 person‐years). With a willingness to pay (WTP) threshold of three times gross domestic product (GDP), Gardasil 4 vaccination for all women living with HIV aged 18–45 years was the most cost‐effective strategy (ICER = US $32,766/QALY gained). This strategy would reduce genital warts by 35.52% (12,467/35,098), cervical cancers by 12.96% (46/355), and cervical cancer deaths by 12.39% (28/226) over the lifetime of the cohort. If the future domestic Cecolin 9 vaccine is priced at 60% of Gardasil 9, vaccinating all women living with HIV aged 18–45 years with Cecolin 9 would be the most cost‐effective strategy (ICER = US $30,493/QALY gained). Improving adherence to antiretroviral therapy for HIV may substantially improve the cost‐effectiveness of both Gardasil 4 and Cecolin 9 vaccination.

Moderate Static Magnet Fields Suppress Ovarian Cancer Metastasis via ROS‐Mediated Oxidative Stress

Metastasis is the leading cause of cancer patient death, which is closely correlated with reactive oxygen species (ROS) levels. It is well known that the effects of ROS on tumors are diverse, depending on ROS concentration and cell type. We found that ovarian cancer cells have significantly lower levels of ROS than normal ovarian cells. Moreover, increased ROS levels in ovarian cancer cells can substantially inhibit their migration and invasion ability. Furthermore, the results show that moderate static magnetic field (SMF) can inhibit ovarian cancer cell migration, invasion, and stemness in a ROS‐dependent manner. RNA sequencing results confirm that SMFs increased the oxidative stress level and reduced the stemness of ovarian cancer cells. Consistently, the expressions of stemness‐related genes were significantly decreased, including hyaluronan receptor (CD44), SRY‐box transcription factor 2 (Sox2), and cell myc proto‐oncogene protein (C‐myc). Furthermore, moderate SMFs provided by a superconducting magnet and permanent magnet have good biosafety and can both inhibit ovarian cancer metastasis in mice. Therefore, our study demonstrates the effects of SMFs on oxidative stress and metastasis in the ovarian cancer cells, which reveals the potential of applying SMF as a physical method in cancer therapy in the future.

Modeling the epidemiological impact and cost-effectiveness of a combined schoolgirl HPV vaccination and cervical cancer screening program among Chinese women

Human papillomavirus (HPV) infection is common in women and also the main cause of cervical cancer. Based on a dynamic compartmental model, we aimed to evaluate the population impact and cost-effectiveness of strategies that combined cervical cancer screening and HPV schoolgirl vaccination for Chinese women. The effectiveness of interventions was assessed by comparing modeled scenarios to the status quo, where a 3-y cervical cancer screening program remained at a 20% coverage and without a universal HPV vaccination program. Our study demonstrated that increasing screening coverage from 20% to 50% would reduce the high-risk HPV (HR-HPV) prevalence to 5.4%, whereas a universal schoolgirl vaccination program using the quadrivalent vaccine (qHPV) with a coverage of 50% would reduce the prevalence to 2.9% by 2069. Scaling-up the cervical screening coverage to 50% will prevent 16,012 (95% CI: 8,791 to 25,913) Disability-Adjusted Life-Years (DALYs) per year, with an incremental cost-effectiveness ratio (ICER) of US$ 10,958 (95% CI: $169 to $26,973)/DALY prevented. At the current qHPV price, vaccinating 50% of school girls will prevent 13,854 (95% CI: 8,355 to 20,776) DALYs/year, but the corresponding incremental cost-effectiveness ratio (ICER, US$ 83,043, 95% CI: $52,234 to $138,025) exceeds cost-effectiveness threshold (i.e., 3 times GDP per-capita of China: $30,792). The qHPV vaccine requires at least a 50% price reduction to be cost-effective. Vaccinating schoolgirls will result in a large population health benefit in the long term, but such a universal HPV vaccination program can only be cost-effective with a substantial price reduction.

The one-dose schedule opens the door to rapid scale-up of HPV vaccination

Prediction of Immunotherapy Response and Prognostic Outcomes for Patients With Ovarian Cancer Using PANoptosis‐Related Genes

BackgroundOvarian cancer (OC) is a lethal malignancy often diagnosed at a late stage with frequent recurrence and immunotherapy resistance. PANoptosis is a novel programmed cell death regulating tumors and immunity. We constructed a prognostic model based on PANoptosis‐related genes (PRGs) and evaluated its value for predicting immunotherapy response and survival in OC.MethodsPRGs linked to OC prognosis were identified from public databases, followed by using the STRING database to develop a protein–protein interaction (PPI) network. The LASSO and multivariate Cox regression analyses were used to construct a risk model, and its predictive value was verified by survival analysis, receiver operator characteristic (ROC) curve, and nomogram. Next, we analyzed the immune microenvironment by combining CIBERSORT, MCP‐counter, and ssGSEA algorithms and assessed the response of patients in different risk groups to immunotherapy using TIDE with immune phenotype score (IPS) methods. GSEA was performed to evaluate the activation status of biological pathways between patients in different risk groups. Finally, we verified the expression and potential biological functions of the key genes using quantitative reverse transcription‐PCR (qRT‐PCR), CCK‐8, scratch, and transwell assays.ResultsA PANoptosis‐related risk model for OC was constructed based on eight genes (PIK3CG, CAMK2A, CD38, NFKB1, PSMA4, PSMA8, PSMB1, and STAT4). The model could accurately evaluate the prognostic outcomes for OC patients, showing a high stability across different datasets. High‐risk patients had lower immune cell infiltration, elevated TIDE, and reduced IPS, which suggested weaker immunotherapy responsiveness and therefore a worse prognosis. In addition, pathway analysis showed that the high‐risk group was mainly enriched in tumor progression–related pathways. In vitro, PIK3CG, CAMK2A, NFKB1, PSMA4, and PSMB1 were upregulated in OC cell lines, and knockdown of PIK3CG notably suppressed the proliferative, migratory, and invasive capabilities of OC cells.ConclusionThe PRG model established in this study may contribute to the assessment of immunotherapeutic response and prognosis for OC patients.