NUCKS1 protein as a marker of aggressivity in PDAC. a single center cohort

Introduction: The ductal adenocarcinoma of the pancreas (PDAC) is an aggressive form of cancer that remains difficult to manage despite intensive research. NUCKS1 (nuclear casein kinase and cyclin dependent kinase substrate1) is a protein present in almost all human cells with an important role in proliferation and DNA repair, demonstrated to have correlated with aggressivity and prognosis in many types of cancer.

Objectives: The objective of this study was to examine the expression of NUCKS1 and p53 protein in a large cohort of PDAC to elucidate if NUCKS1, similar to p53, can be used as a potential marker to determine prognosis.

Methods: The patient collective is comprised of 192 patients with PDAC that underwent surgery at the University Clinic of Düsseldorf between September 2003 and January 2017. Tissue microarrays (TMA) composed of pancreatic tumor tissue, lymph node metastasis and normal pancreatic tissue were stained for NUCS1 and p53 for each patient. The IHC staining results were evaluated using the IRS (immune reactive score) in case of the NUCKS1 staining and a proprietary score for the p53 staining.

Results: 192 patients were enrolled (93 female and 99 male, mean age 68yrs), and 175 presented with T3 tumors. The patient collective was divided into two groups according to the NUCKS1 staining: above or beneath the median of the IRS. An assessment was made between the two groups concerning the clinical and histopthological factors, and statistical differences were discovered. A significantly higher expression of NUCKS1 was shown in less aberrant (≤G2) tumors, as well as a tendency for a longer survival (p=0,051, Log-Rank Test). Similarly, patients without distant metastases (M0) showed a significantly higher expression of nuclear NUCKS1 in lymph node metastases and the cytoplasm of normal tissue, compared to patients with distant metastases (M1). There was no relevant co-expression of p53 and NUCKS1, as well as no correlation between aberrant p53 protein and clinicopathological characteristics. In our patient collective there was no statistically significant difference in the 5-year OS based on NUCKS1 or p53 expression.

Conclusions: The higher NUCKS1 expression seems to correlate to a less aggressive tumor phenotype (≤G2, M0). Surprisingly, an aberrant p53 expression did not correlate with NUCKS1 expression or worse OS. NUCKS1 seems to be rather a protective factor in PDAC patients, possibly due to the known role of NUCKS1 in genome repair.

 

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Publication History

Article published online:
04 September 2025