High JAK2 Protein Expression Predicts a Poor Prognosis in Patients with Resectable Pancreatic Ductal Adenocarcinoma

Abstract

Background. Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide. The JAK/STAT signaling pathway is involved in pancreatic cancer tumorigenesis. However, the prognostic value of JAK2 expression in resectable PDAC is unclear. Method. In this study, we performed a clinicopathological analysis of 62 resectable PDAC cases with a primary focus on survival. JAK2 expression was examined by immunohistochemistry. The relationship between JAK2 expression and clinicopathological features and prognosis was analyzed. Results. Survival curve analyses revealed that high levels of JAK2 expression predict a poor prognosis in resectable PDAC patients. Multivariate analysis confirmed that JAK2 expression can predict the prognosis of PDAC. Conclusions. Assessment of JAK2 protein expression may be a promising method to predict prognosis in patients with resectable PDAC.

Inhibition of JAK2/STAT3 signaling pathway by panaxadiol limits the progression of pancreatic cancer

“…To explore the underlying pro-apoptosis mechanism of panaxadiol, we performed molecular docking and western blot. According to the literature, blockage of JAK2-STAT3 signaling pathway was associated with apoptosis of pancreatic cancer [ 14 , 15 ], and the high expression of JAK2 in pancreatic cancer patients predicts an unfavorable prognosis in most cases [ 16 ]. In molecular docking analysis ( Figure 5A and 5B ), panaxadiol shows promising affinity with STAT3 and the lowest binding energy which means the best binding affinity with the target site was −5.7 (kcal/mol) among them.…”

“…In previous researches, JAK2-STAT3 signal pathway has been proved to play a critical role in tumorigenesis, proliferation, stroma modification, chemoresistance, immune cell infiltration, patient survival time in pancreatic cancer [ 16 , 29 , 30 ]. After receiving the stimulation of the upstream signal, JAK2 is activated by tyrosine phosphorylation of the receptor, and this also leads to phosphorylation of STAT3.…”

“…Then, P-STAT3 forms a dimer and entry the nucleus to regulate various target genes. It was documented that the expression of JAK2 and STAT3 was particularly high in pancreatic cancer tissues compared with para-cancerous tissues and it was intensely associated with a poor prognosis in pancreatic cancer patients [ 16 ]. According to Wang et al [ 7 ], JAK2-STAT3 signal pathway was involved in the anti-tumor effect of panaxadiol in colon cancer.…”

The molecular biology of pancreatic adenocarcinoma: translational challenges and clinical perspectives

“…High JAK2 expression predicts a poor prognosis in patients with PDAC. 80 Several studies have shown that the JAK/STAT pathway is involved in inflammatory processes in pancreatic cancer. Both type 1 (i.e., IFNα and IFNβ) and type 2 (i.e., IFNγ) interferons can upregulate programmed cell death 1-ligand 1 (PD-L1) expression via the JAK-STAT signaling pathway in pancreatic cancer.…”

The State-of-the-Art of Phase II/III Clinical Trials for Targeted Pancreatic Cancer Therapies

“…The Janus-associated kinase-signal transducer and activator of transcription (JAK-STAT) pathway is involved in the development of multiple human cancers [88]. Four JAK and seven STAT family members have been described in humans, although significant elevations in expression and activation of JAK1/2 and STAT3, in particular, have been observed in pancreatic cancer patients [89][90][91]. Overexpression of JAK-STAT pathway components, such as IL-6, EGFR, and Src, have also been seen in pancreatic cancer [87].…”