Effects of Krüppel-like factor 4 mutation on the clinicopathological characteristics and its related protein expressions in intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND/

OBJECTIVES

Krüppel-like factor 4 (KLF4) hotspot mutations are linked to non-invasive intraductal papillary mucinous neoplasms (IPMNs); however, the molecular mechanisms driving their progression remain unclear. Therefore, in this study, we aimed to identify the signaling pathways associated with KLF4 mutations and their roles in IPMNs.

METHODS

Thirty-three resected specimens of IPMNs were collected. Associations between genetic alterations in KLF4 and the expression levels of KLF4 protein as well as its related signaling proteins, including p21, p27, and cyclin D, were assessed.

RESULTS

KLF4 mutations were found in eight specimens of IPMNs (24 %), all of which were non-invasive lesions and non-intestinal type; of them, seven (87.5 %) showed GNAS mutations. p21 expression was significantly elevated in KLF4-mutated IPMNs (p < 0.01), whereas p27 and cyclin D1 levels were not significantly altered compared with KLF4 wild-type IPMNs. KLF4 and p21 expression levels were significantly elevated in non-invasive lesions compared with invasive lesions (p < 0.05). Higher KLF4 expression was observed in GNAS-mutated IPMNs than in GNAS wild-type IPMNs (p < 0.05).

CONCLUSIONS

KLF4 mutations might enhance p21 expression, possibly influencing the indolent characteristics of non-invasive IPMNs and providing a new biomarker strategy for risk stratification in patients with IPMNs.