Zeqing Du

Smoking exposure and cervical cancer risk: Integrating observational and genetic evidence

Objective To investigate the relationship between smoking exposure and cervical cancer risk by integrating observational and genetic evidence. Methods We analyzed data from the National Health and Nutrition Examination Survey (1999–2018) and performed a genetic instrumental variable analysis using genome-wide association studies data. Smoking exposure was assessed using self-reported status and serum cotinine concentrations. Logistic regression models were used to evaluate observational associations, while inverse variance weighting was used for genetic analysis. Results Observational analysis showed that current smokers had a significantly higher cervical cancer risk than nonsmokers and former smokers (adjusted odds ratio = 3.05, 95% confidence interval: 1.61–5.78, p < 0.001). Higher serum cotinine concentrations were also positively associated with cervical cancer risk. Genetic analysis further supported a causal link between smoking exposure and cervical cancer. Conclusions Smoking exposure significantly increases cervical cancer risk, emphasizing the importance of smoking cessation for prevention of cervical cancer. Incorporating tobacco control into cervical cancer prevention strategies could reduce disease burden.

Successful Diagnosis and Treatment of Early Postpartum Choriocarcinoma

ABSTRACTBackgroundPostpartum placental choriocarcinoma is a rare gestational trophoblastic tumor, with an incidence of approximately one in 50 000. Patients often present with persistent postpartum hemorrhage, which can lead to delayed diagnosis, hematogenous metastasis, and ultimately, a poor prognosis.CaseA 35‐year‐old woman was admitted to the Emergency Department 39 days after a cesarean section due to persistent heavy vaginal bleeding. Initial evaluation revealed a serum β‐human chorionic gonadotropin (β‐hCG) level of 7868 mIU/mL, transvaginal ultrasound identified a vascularized uterine mass with myometrial invasion, and MRI suggested residual tissue implantation. Following exclusion of retained products of conception, postpartum choriocarcinoma was suspected. The patient underwent five cycles of FAV chemotherapy (fluorouracil + actinomycin D + vincristine), resulting in undetectable β‐hCG levels and resolution of imaging findings after two cycles. Three additional consolidation cycles were administered, with complete remission confirmed at the final follow‐up.ConclusionPregnancy‐related causes must always be ruled out in women of childbearing age who present with irregular vaginal bleeding, even during the postpartum and lactation periods. In patients with postpartum bleeding, vigilance should be heightened to rule out the possibility of a pregnancy‐related Sertoli cell tumor.

5-Methylcytosine methylation predicts cervical cancer prognosis, shaping immune cell infiltration

Background Epigenetics, encompassing DNA and RNA modifications, has emerged as a prominent area of research in the post-genomic era. Numerous studies have elucidated the impact of epigenetics on tumor regulation. However, the methylation patterns of 5-methylcytosine in cervical cancer as well as its role in the tumor microenvironment and immunotherapy remain poorly understood. Methods Utilizing a comprehensive dataset encompassing samples from 306 patients with cervical cancer from The Cancer Genome Atlas and Gene Expression Omnibus repositories, we conducted an in-depth analysis to evaluate the potential association between the modification patterns of 5-methylcytosine and the infiltration of cells within the tumor microenvironment, taking into account 11 regulators of 5-methylcytosine modification. Subsequently, we employed stepwise regression and Least Absolute Shrinkage and Selection Operator Cox regression to quantify 5-methylcytosine modification patterns in patients with cervical squamous cell carcinoma and endocervical adenocarcinoma, yielding the 5-methylcytosine score. Our study explored the link between the 5-methylcytosine score and clinical characteristics as well as prognostic outcomes in patients with cervical squamous cell carcinoma and endocervical adenocarcinoma. Results A comprehensive analysis of 306 patients with cervical cancer revealed two distinct 5-methylcytosine modification patterns, henceforth labeled as 5-methylcytosine clusters A and B. These clusters exhibited distinct immunological profiles and biological attributes, with 5-methylcytosine cluster A exhibiting a higher degree of immune cell infiltration. Utilizing univariate Cox regression analysis, we identified 367 genes regulated by 5-methylcytosine that were significantly correlated with patient prognosis. This analysis further stratified the samples into three distinct genomic subtypes. Survival analyses indicated that patients belonging to gene cluster C exhibited more favorable survival outcomes than those belonging to gene clusters A and B. Intriguingly, most 5-methylcytosine regulatory factors had higher expression levels in gene cluster B than in gene cluster A. Gene set enrichment analysis of a single sample revealed elevated immune cell infiltration within gene cluster B, indicating a stronger immune response in this cluster. The 5-methylcytosine score feature was utilized to determine the 5-methylcytosine modification pattern in cervical cancer, revealing that patients with low 5-methylcytosine scores exhibited better survival rates, whereas those with high scores had increased mutation frequencies and better treatment responses. Conclusions This research underscores the key role of 5-methylcytosine modification patterns in cervical cancer. Analysis of these patterns will deepen our understanding of the cervical cancer tumor microenvironment, paving the way for the development of more refined and effective immunotherapy strategies.