title: aPKCλ/ι is a beneficial prognostic marker for pancreatic neoplasms.
abstract: Pancreatic cancer is a lethal disease. Overall survival is typically 6 months from diagnosis. Determination of prognostic factors in pancreatic cancer that would allow identification of patients who could potentially benefit from aggressive treatment is important. However, until date, there are no established reliable prognostic factors for pancreatic cancer patients. Herein, we propose a beneficial biomarker which is significantly correlated with the prognosis in pancreatic cancer patients. Atypical protein kinase C λ/ι (aPKCλ/ι) is overexpressed and has been implicated in the progression of several cancers. We tested the expression levels of aPKCλ/ι in two types of pancreatic neoplasm, pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs), by immunohistochemistry. Examination of the aPKCλ/ι expression levels in surgically resected specimens of PDCA (n = 115) demonstrated that the expression levels of aPKCλ/ιin PDAC had prognostic implications, independent of the Tumor-Node-Metastasis classification and World Health Organization tumor grade. In the case of IPMNs (n = 46) also, the expression levels of aPKCλ/ιin IPMN were found to be of prognostic importance, independent of the World Health Organization histological grade or morphological type. Interestingly, high expression levels of aPKCλ/ι were significantly correlated with a worse histological grade (p = 0.010) and advanced stage of the tumor (p = 0.0050) in IPMN patients. These findings suggest that high expression levels of aPKCλ/ι could be involved in the malignant transformation of IPMNs. Based on these observations, we propose the expression level of aPKCλ/ι as a prognostic marker common to different types of pancreatic neoplasms.
authors.affiliation: Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kato
authors.forename: Kazunori
authors.initials: K
authors.lastname: Akimoto
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagashima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishiguro
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kubota
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Hosono
authors.forename: Seitaro
authors.initials: S
authors.lastname: Watanabe
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sekino
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Sato
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sasaki
authors.forename: Noboru
authors.initials: N
authors.lastname: Nakaigawa
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kubota
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Inayama
authors.forename: Itaru
authors.initials: I
authors.lastname: Endo
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohno
authors.forename: Shin
authors.initials: S
authors.lastname: Maeda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D011493:Protein Kinase C / Q000378:metabolism*; D000099293:Protein Kinase C-lambda
chemical_list: D014408:Biomarkers, Tumor; D007527:Isoenzymes; D011493:Protein Kinase C; D000099293:Protein Kinase C-lambda
keywords: Atypical protein kinase C λ/ι; Intraductal papillary mucinous neoplasms; Pancreatic ductal adenocarcinoma