Genomic landscape and clinicopathological predictors of survival in gallbladder cancer.

BACKGROUND

Gallbladder cancer (GBC) is highly aggressive with a disproportionate incidence in North India. This study integrates clinicopathological and genomic profiles to identify drivers of mortality and recurrence in a regional cohort.

METHODS

Retrospective analysis was conducted on 35 GBC patients using targeted Next-Generation Sequencing (NGS). Survival analysis (OS and DFS) and Cox regression identified independent prognostic factors using Python-based pipelines.

RESULTS

The cohort showed a 97% mortality rate and a 7-month median survival. At diagnosis, 80% presented with advanced disease (Stages III-IV). Somatic mutations occurred in 60% of patients, primarily TP53 (31.4%) and KRAS (14.3%). While mutation status did not significantly impact OS (p = 0.8974), multivariable Cox regression identified elevated CA19-9 (p = 0.028) and age > 40 years (p = 0.009) as independent mortality predictors. In the DFS model, KRAS mutation demonstrated a strong trend toward higher recurrence risk (HR = 7.54, p = 0.064).

CONCLUSION

High mortality and poor survival in North Indian GBC are driven by late-stage presentation. While CA19-9 and age are robust mortality predictors, KRAS mutations signify rapid recurrence. These findings emphasize the need for localized genomic screening to guide precision oncology in high-burden populations.