X-linked inhibitor of apoptosis protein is a prognostic marker for a favorable outcome in three identified subsets in resectable adenocarcinoma of the pancreas.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is currently one of the leading causes of cancer death worldwide. Therefore, building further subgroups as well as enabling individual patient therapy and diagnostics are needed. X-linked inhibitor of apoptosis protein (XIAP) is known to modulate apoptotic and inflammatory pathways. Its expression was found to correlate with patients' survival in other tumor entities. This study aims to examine the role of XIAP in patients with PDAC in relation to the inflammatory microenvironment.

Methods: The PANCALYZE multicenter study group included 257 patients with PDAC. Paraffin-embedded tumor samples were stained immunohistochemically for CD3, CD20, CD38, CD56, CD66b, CD117, and CD163 and XIAP. These stainings were further analyzed digitally with QuPath and survival analyses were done.

Results: XIAP-positive patients with T-cell, respectively, neutrophil enriched tumors survived significantly longer compared to XIAP-negative patients (CD3: 37.6 vs. 24.6 months, p = 0.028; CD66b: 34.1 vs. 14.9 months, p = 0.027). Additionally, XIAP-positive patients showed better survival in the lymph node-negative population (48.4 vs. 24.2 months, p = 0.019). Regarding the total population, our findings did not show a correlation between XIAP expression and survival. In multivariate cox regression analyzes XIAP proves to be an independent factor for better survival in the identified subgroups (CD3: p = 0.043; CD66b: p = 0.012, N0: p = 0.040).

Conclusion: We found XIAP-positive subgroups with significantly better survival in patients with PDAC in T-cell-rich, neutrophil-rich, or lymph node-negative cohorts. This could lead to further individualized cancer treatment with less aggressive therapy protocols for XIAP-positive tumors or more intensive follow-up for XIAP-negative tumors.