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Background <p>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.</p> Methods <p>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.</p> Results <p>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 (<i>p</i> = 0.8974), multivariable Cox regression identified elevated CA19-9 (<i>p</i> = 0.028) and age &gt; 40&#xa0;years (<i>p</i> = 0.009) as independent mortality predictors. In the DFS model, KRAS mutation demonstrated a strong trend toward higher recurrence risk (HR = 7.54, <i>p</i> = 0.064).</p> Conclusion <p>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.</p>

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Genomic landscape and clinicopathological predictors of survival in gallbladder cancer

  • 期刊论文

  • 发表日期：

    2026年4月25日

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  • Manoj Pandey,
  • Monika Rajput,
  • Satya Vijay Chigurupati,
  • Madhumita Tripathi

摘要

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.