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Plasma ctDNA TP53 Mutation and Breast Cancer Prognosis: A Systematic Review and Meta-Analysis
Medical Journal of Peking Union Medical College Hospital 2025, 16(4): 874-885
Published: 21 July 2025
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Objective

To analyze the association between plasma circulating tumor DNA (ctDNA) TP53 mutation status and survival outcomes in breast cancer patients.

Methods

PubMed, Embase, and the Cochrane Library were searched for relevant literature published between 2000 and 2025, examining the impact of plasma ctDNA TP53 mutations on survival outcomes in breast cancer patients, including overall survival (OS), progression-free survival (PFS), or disease-free survival (DFS).Two researchers independently screened the literature according to predefined inclusion and exclusion criteria and extracted relevant data.The Newcastle-Ottawa scale and Cochrane Risk of Bias Assessment Tool were used to evaluate study quality.Meta-analysis, publication bias assessment, and sensitivity analysis were performed using Review Manager 5.3 and STATA 18.0 software.

Results

A total of 14 studies (13 cohort studies and 1 randomized controlled trial) involving 3521 breast cancer patients were included, among whom 921 had TP53 mutations.All studies were assessed as high-quality or low-risk.The random-effects model demonstrated that TP53 mutations were significantly associated with poorer OS (I2=77%, HR=1.82, 95% CI: 1.15-2.88, P=0.010), PFS (I2=63%, HR=1.68, 95% CI: 1.30-2.17, P < 0.001), and DFS (I2=85%, HR=1.98, 95% CI: 1.05-3.75, P=0.040).Funnel plots indicated no significant publication bias, and sensitivity analysis confirmed the stability and reliability of the results.Subgroup analyses based on study design, breast cancer stage and molecular subtype revealed that TP53 mutations were associated with worse prognosis in prospective studies (OS: HR=2.32, 95% CI: 1.84-2.92, P < 0.001;PFS: HR=1.83, 95% CI: 1.47-2.27, P < 0.001), metastatic/advanced breast cancer (OS: HR=2.03, 95% CI: 1.44-2.87, P < 0.001;PFS: HR=1.90, 95% CI: 1.57-2.31, P < 0.001), and hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+HER2-) patients (OS: HR=2.11, 95% CI: 1.56-2.85, P < 0.001;PFS: HR=1.94, 95% CI: 1.62-2.33, P < 0.001).Among different treatment regimens, patients with TP53 mutations receiving trastuzumab combined with paclitaxel exhibited relatively better prognosis (PFS: HR=0.08, 95% CI: 0.02-0.30, P < 0.001).

Conclusion

Plasma ctDNA TP53 mutations are closely associated with survival outcomes in breast cancer patients and may serve as a potential predictor of poor prognosis, providing support for clinical management and prognostic assessment.

Issue
Association Between Obesity-Related Metabolic Indices and Knee Osteoarthritis: A Cross-Sectional Study in Middle-Aged and Older Chinese Adults
Medical Journal of Peking Union Medical College Hospital 2026, 17(1): 172-180
Published: 28 May 2025
Abstract PDF (1.3 MB) Collect
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Objective

To investigate the association between obesity-related metabolic indices and the risk of knee osteoarthritis(KOA) in middle-aged and older Chinese adults(≥45 years) using data from the China Health and Retirement Longitudinal Study(CHARLS).

Methods

Data from two CHARLS survey waves(2011—2012 and 2015—2016) were analyzed. Obesity indices—including body mass index(BMI), waist circumference(WC), waist-to-height ratio(WHtR), visceral adiposity index(VAI), a body shape index(ABSI), body roundness index(BRI), lipid accumulation product(LAP), conicity index(CI), and Chinese visceral adiposity index(CVAI)-and metabolic indices-triglyceride glucose index(TyG), TyG-BMI, TyG-WC, and TyG-WHtR-were collected. Covariates comprised demographic characteristics, lifestyle factors, and health status. Three multivariate logistic regression models were constructed. Sex-subgroup analyses assessed heterogeneity, and receiver operating characteristic(ROC) curves with area under the curve(AUC) were used to evaluate diagnostic performance.

Results

Among 9527 participants, the prevalence of KOA was 9.59%(914/9527). After adjusting for confounders, linear regression revealed significant positive associations between KOA and BMI(OR=1.02, 95% CI: 1.00-1.04, P=0.048), BRI(OR=1.06, 95% CI: 1.01-1.13, P=0.030), LAP(OR=1.03, 95% CI: 1.00-1.05, P=0.020), TyG-BMI(OR=1.02, 95% CI: 1.00-1.05, P=0.020), and TyG-WHtR(OR=1.13, 95% CI: 1.02-1.25, P=0.020). Sex-stratified analyses showed that in women, BMI(OR=1.03, 95% CI: 1.01-1.06, P=0.020), WHtR(OR=1.18, 95% CI: 1.02-1.36, P=0.020), BRI(OR=1.08, 95% CI: 1.01-1.16, P=0.020), LAP(OR=1.03, 95% CI: 1.01-1.06, P=0.020), CVAI(OR=1.04, 95% CI: 1.01-1.07, P=0.009), TyG-BMI(OR=1.03, 95% CI: 1.01-1.06, P=0.006), TyG-WC(OR=1.10, 95% CI: 1.01-1.19, P=0.02), and TyG-WHtR(OR=1.18, 95% CI: 1.04-1.34, P=0.010) were positively associated with KOA, whereas no significant associations were observed in men(P > 0.05 for all indices). Significant sex interactions were found for WC(P=0.010), CVAI(P=0.002), and TyG-WC(P=0.020). ROC analysis indicated limited diagnostic utility for all indices[BRI(AUC=0.547, 95% CI: 0.526-0.567), TyG-WHtR(AUC=0.544, 95% CI: 0.524-0.564), others ≤0.530].

Conclusions

BMI, BRI, LAP, TyG-BMI, and TyG-WHtR may serve as auxiliary indicators for KOA risk assessment in middle-aged and older women, but their standalone screening value remains modest. Clinical evaluation and integration with other risk factors are recommended for comprehensive risk stratification.

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