BMC Cancer最新文献

Background: Gastric adenocarcinoma with peritoneal metastasis (PM) has a poor prognosis, yet clinical outcomes vary significantly. This study aimed to identify independent prognostic determinants of PM-specific survival (PM-OS), focusing on tumor biology and disease burden surrogate.

Methods: We retrospectively analyzed 166 patients with gastric adenocarcinoma and PM treated at a single center between 2015 and 2024. Prognostic factors were evaluated using multivariable Cox proportional hazards models. To mitigate immortal time bias and confounding by indication, receipt of systemic therapy was excluded from the primary multivariable model.

Results: The median PM-OS was 8.2 months (95% CI, 6.63-9.79). Patients diagnosed via surgical exploration (radiologically occult) achieved a significantly longer median PM-OS compared to those diagnosed radiologically (13.6 vs. 7.4 months; p = 0.003). In multivariable analysis, HER2 positivity (HR0.312, 95% CI 0.164-0.593; p < 0.001) and surgical diagnosis (HR 0.555, 95% CI 0.338-0.913; p = 0.020), interpreted as a surrogate for radiologically occult/low tumor burden, were identified as independent predictors of improved survival. Additionally, an optimized CA 19 - 9 cutoff (> 175.4 U/mL), unlike the standard threshold, significantly stratified survival. Traditional factors, including signet-ring cell histology and age, did not retain independent significance.In sensitivity analysis including systemic therapy, treatment was strongly associated with survival and the prognostic significance of HER2 and diagnostic context remained.

Conclusion: Survival in gastric PM is fundamentally driven by HER2 status and the extent of PM. Surgical detection identifies a subgroup with limited, occult disease who achieve superior outcomes compared to those with radiologically overt metastases. Furthermore, the magnitude of biomarker elevation, rather than mere positivity, serves as a critical stratifier. These findings support a paradigm shift towards burden-based risk stratification to guide treatment intensity and clinical trial eligibility.

Background: This study aimed to identify prognostic biomarkers for gastric cancer (GC) by analyzing the methylation status of multiple tumor suppressor genes.

Methods: Using the Epi-TOP™ methylation detection system, we analyzed 51 genes in 169 matched tumor and adjacent normal tissue samples. Methylation levels were quantified as Percent Methylated Reference (PMR) in tumor (PMR-T) and normal (PMR-N) tissues; the differential methylation (PMR-D) was also calculated.

Result: Tumor tissues exhibited significantly higher DNA methylation levels than matched normal tissues across 51 tumor suppressor genes (all p < 0.001). Clustering analysis based on PMR-T identified four epigenetic subtypes associated with known molecular classifications (epithelial-mesenchymal transition (EMT) and microsatellite instability-high (MSI-H)) and overall survival (p = 0.030). In contrast, clustering based on PMR-N showed no significant association with molecular subtypes or survival outcomes, suggesting limited prognostic relevance. Two prognostic gene panels were constructed: one PMR-T-based panel (ALX, BMP3, CDKN2A, MINT25, PTGDR) and another PMR-D-based panel (ADCYAP1, SOCS1, SEPTIN9, CDKN2B). Both panels independently predicted overall survival in multivariate Cox regression. The PMR-D panel demonstrated stronger prognostic performance (hazard ratio (HR) = 0.329, p = 0.002), while the PMR-T panel also demonstrated significant prognostic value (HR = 0.512, p = 0.012), highlighting that tumor methylation profiles alone may provide meaningful survival predictions for patients with GC.

Conclusion: This study demonstrates that tumor-specific DNA methylation changes, particularly when evaluated using multi-gene panels can enhance prognostic stratification in GC. These findings support the potential use of methylation-based biomarkers for personalized management of GC.