Investigating the prognostic value of KOC (K homology domain containing protein overexpressed in cancer) overexpression after curative intent resection of pancreatic ductal adenocarcinoma.

Background: Pancreatic adenocarcinoma (PDAC) is now the third leading cause of cancer mortality in the United States. More than 80% of patients present with distant metastasis precluding surgical eligibility. Even among patients with localized disease deemed eligible for surgical resection, the median survival is only 22.8 months due to high recurrence rates. Identification of a biomarker correlated with patient specific prognosis upon initial diagnosis can serve as a way to individualize treatment options.

Methods: We performed a retrospective cohort study analyzing pathology of patients who underwent curative intent surgery for PDAC at Geisinger Medical Center from 1998-2011 to identify whether the expression of KOC can be predictive of patient specific prognosis. Tissue microarrays of specimens were assessed by immunohistochemistry.

Results: A total of 62 patients are included. Comparisons between groups on overall survival (OS) and progression free survival (PFS) are estimated using the Kaplan-Meier method and the log-rank test. Each biomarker was represented as low and high expression by categorizing the expression score at <4+ or >4+, based on intensity and extent of cells stained. 40 deaths occurred in the sample. Distant metastasis and differentiation (well/moderate poor) were related to OS (P=0.0120, P=0.0086). Twenty-nine patients progressed in their disease. High/low KOC expression were significantly related to PFS (P=0.0556). Patients with a high KOC expression were more than 2 times more likely to progress compared to those with a low KOC expression (HR =2.04; 95% CI: 0.97, 4.29).

Conclusions: Our data is suggestive of KOC being a useful prognostic biomarker for identifying those patients with PDAC who have a high risk for early progression and distant metastasis. Larger studies are needed to determine whether KOC can be a therapeutic target in the treatment of pancreatic cancer. Furthermore, considering high KOC expressers had a worse PFS than their counterparts, investigation regarding the use of KOC expression as a biomarker to preselect patients who may benefit most from neoadjuvant chemotherapy is warranted.