p21-activated kinase signalling in pancreatic cancer: New insights into tumour biology and immune modulation

Wang, Kai; Baldwin, Graham S.; Nikfarjam, Mehrdad; He, Hong

doi:10.3748/wjg.v24.i33.3709

Cited by 30 publications

(21 citation statements)

References 145 publications

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“…Pancreatic cancer is one of the malignant tumors with the worst prognosis. Due to its difficult early diagnosis and treatment, the 5‐year survival rate is less than 1% (Li et al, ; Wang, Baldwin, Nikfarjam, & He, ). Because pancreatic cancer is lack of obvious early symptoms, it is generally diagnosed in the advanced stages (Draper, ; Kitagawa et al, ).…”

Section: Introductionmentioning

confidence: 99%

KIF18B promotes the proliferation of pancreatic ductal adenocarcinoma via activating the expression of CDCA8

Liu

Zhang

et al. 2019

Journal Cellular Physiology

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Pancreatic cancer is one of the malignant tumors with the worst prognosis, and the 5-year survival rate of this disease is less than 1%. About 90% of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), and targeting therapy has become a promising treatment for PDAC in recent years. To improve the survival rate, novel therapeutic targets for PDAC are still urgently needed. KIF18B was initially identified as a member of the kinesin family and involved in multiple cellular processes, such as separation of chromosomes in mitosis. Recently, it was found that KIF18B was involved in the growth and development of multiple cancers. However, the potential link between KIF18B and PDAC is still unclear. In this study, we demonstrated that KIF18B was highly expressed in human PDAC tissues, and related with the poor prognosis and clinical features, such as tumor size (*p = .013) and pTNM stage (*p = .025), of patients with PDAC. We further found that KIF18B knockdown blocked the cell proliferation of PDAC in vitro and in vivo, and the cell cycle was arrested caused by KIF18B depletion. Additionally, we also found that KIF18B bound to the promoter region of the cell division cycle associated 8 and thus activated its transcription. Taken together, this study explored the molecular mechanism underlying KIF18B promoting PDAC and provided a novel therapeutic target of this disease. K E Y W O R D SCDCA8, KIF18B, pancreatic ductal adenocarcinoma, proliferation, therapeutic target

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Section: Introductionmentioning

confidence: 99%

KIF18B promotes the proliferation of pancreatic ductal adenocarcinoma via activating the expression of CDCA8

Liu

Zhang

et al. 2019

Journal Cellular Physiology

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“…The ve-year survival rate is less than 8% 1 . Surgery is the most important and comprehensive treatment for pancreatic cancer, and most patients have recurrence and metastasis earlier after operation.…”

Section: Introductionmentioning

confidence: 93%

Prognostic value of eight immune gene signatures in pancreatic cancer patients

Wang

Zhang

Wang

et al. 2020

Preprint

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BackgroundPancreatic cancer is one of the most common malignant tumors of the digestive tract, and it has a poor prognosis. Traditional methods are not effective to accurately assess the prognosis of patients with pancreatic cancer. Immunotherapy is a new promising approach for the treatment of pancreatic cancer; however, some patients do not respond well to immunotherapy, which may be related to tumor microenvironment regulation. In this study, we use gene expression database to mine important immune genes and establish a prognostic prediction model for pancreatic cancer patients. We hope to provide a feasible method to evaluate the prognosis of pancreatic cancer and provide valuable targets for pancreatic cancer immunotherapy.ResultsWe used univariate Cox proportional hazard regression analysis, the least absolute shrinkage and selection operator (LASSO), and multivariate COX regression analysis to screen 8 genes related to prognosis from the 314 immune-related genes, and used them to construct a new clinical prediction model in the TCGA pancreatic cancer cohort. Subsequently, we evaluated the prognostic value of the model. The Kaplan–Meier cumulative curve showed that patients with low risk scores survived significantly longer than patients with high risk scores. The area under the ROC curve (AUC value) of the risk score was 0.755.The univariate COX analysis showed that the risk score was significantly related to overall survival (OS) (HR = 1.406, 95% CI = 1.237 ~ 1.598, P <0.001), and multivariate analysis showed that the risk score was an independent prognostic factor (HR = 1.400 95% CI = 1.287 ~ 1.522, P <0.001). Correlation analysis found that immune genes are closely related to tumor immune microenvironment.ConclusionsBased on the TCGA-PAAD cohort, we identified immune-related markers with independent prognostic significance, validated, and analyzed their biological functions, to provide a feasible method for the prognosis of pancreatic cancer and provide potentially valuable targets for pancreatic cancer immunotherapy.

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“…The dectin1-galectin9 axis is central in directing the differentiation of TAM to a M2like phenotype, which suffices for reprogramming CD4+ and CD8+ T-cells (749). Finally, we list some reviews helpful as starting information on PaCa-selective metabolic changes that affect immune responses in PaCa (739,(750)(751)(752)(753)(754).…”

Section: Tregmentioning

confidence: 99%