Angiopoietin-like Protein 2 is a Useful Biomarker for Pancreatic Cancer that is Associated with Type 2 Diabetes Mellitus and Inflammation

Yoshinaga, Takuma; Niou, Tatsuyuki; Niihara, Toru; Kajiya, Yoriko; Hori, Emiko; Tomiyoshi, Ayako; Tokudome, Erena; Nishimata, Hiroto; Takei, Takayuki; Yoshida, Masahiro

doi:10.7150/jca.25404

Cited by 9 publications

(7 citation statements)

References 26 publications

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“…We also previously demonstrated that suppressing ANGPTL2 expression in tumor cells inhibits tumor metastasis in a xenograft mouse model, suggesting that tumor cell-derived ANGPTL2 could be a novel therapeutic target against tumor metastasis (Endo et al 2012;Odagiri et al 2014). Furthermore, serum ANGPTL2 reportedly serves as a diagnostic biomarker for some cancers, such as colon and pancreatic cancers (Toiyama et al 2014;Yoshinaga et al 2015Yoshinaga et al , 2018. The present study also demonstrated that ANGPTL2 deficiency in renal tubular epithelial cells slows progression of kidney cancer in Xp11 tRCC model mice.…”

Section: Discussionsupporting

confidence: 74%

Dual functions of angiopoietin-like protein 2 signaling in tumor progression and anti-tumor immunity

et al. 2019

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Angiopoietin-like protein 2 (ANGPTL2) is a secreted glycoprotein homologous to angiopoietins. Previous studies suggest that tumor cell-derived ANGPTL2 has tumor-promoting function. Here, we conducted mechanistic analysis comparing ANGPTL2 function in cancer progression in a murine syngeneic model of melanoma and a mouse model of translocation renal cell carcinoma (tRCC). ANGPTL2 deficiency in tumor cells slowed tRCC progression, supporting a tumor-promoting role. However, systemic ablation of ANGPTL2 accelerated tRCC progression, supporting a tumor-suppressing role. The syngeneic model also demonstrated a tumor-suppressing role of ANGPTL2 in host tumor microenvironmental cells. Furthermore, the syngeneic model showed that PDGFRα+ fibroblasts in the tumor microenvironment express abundant ANGPTL2 and contribute to tumor suppression. Moreover, host ANGPTL2 facilitates CD8+ T-cell cross-priming and enhances anti-tumor immune responses. Importantly, ANGPTL2 activates dendritic cells through PIR-B–NOTCH signaling and enhances tumor vaccine efficacy. Our study provides strong evidence that ANGPTL2 can function in either tumor promotion or suppression, depending on what cell type it is expressed in.

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Section: Discussionsupporting

confidence: 74%

Dual functions of angiopoietin-like protein 2 signaling in tumor progression and anti-tumor immunity

et al. 2019

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“…In this study, descriptive analysis of the general information of patients by Chi square test among the groups (case group, positive control group and negative control group) showed statistical differences in age, gender and diabetes. Based on logistic multivariate regression analysis, it was concluded that the difference of diabetes history between the case group and the positive control group was statistically signi cant, possibly because diabetes is one of the risk factors of pancreatic cancer [34,35]. Based on logistic multivariate regression analysis, we found that the difference of gender and diabetes between the case group and the negative control group was even more statistically signi cant.…”

Section: Discussionmentioning

confidence: 81%

A Case-Control Study on the Relationship Between Cholecystectomy and Cholangiocarcinoma in China

Zhu¹,

Fu²,

Zhang³

et al. 2020

Preprint

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Aims: The present study aimed to explore the correlation between cholecystectomy and cholangiocarcinoma, and to provide preliminary clinical basis for precise cholecystectomy in China.Methods: We conducted a retrospective analysis of 9744 patients with cholangiocarcinoma, colon cancer, pancreatic cancer, femoral fracture, and hepatic hemangioma diagnosed in Xijing hospital from August 2008 to August 2018. They were divided into three groups: case group (1749 cases of cholangiocarcinoma), positive control group (3137 cases of colon cancer and 1950 cases of pancreatic cancer), negative control group (1794 cases of femoral fracture and 1114 cases of hepatic hemangioma). We collected the general information (gender, age), past medical history, cholecystectomy history from the patients, and these data were analyzed by chi-square test and logistic regression analysis. Results: The cholecystectomy rate of the case group was significantly higher than that of the positive control group and the negative control group by chi-square test (p<0.025). The cholecystectomy rate and the history of cholecystolithiasis were analyzed by logistic multivariate regression analysis. The OR values of cholecystectomy rate were 1.553 (95%CI: 1.311-1.840) and 3.181 (95%CI: 2.561-3.951), respectively, and the difference was statistically significant (p<0.000). The OR values of the history of cholecystolithiasis were 2.460 (95%CI: 2.093-2.890) and 5.426 (95%CI: 4.325-6.809), respectively, and the difference was statistically significant (p<0.000). In case group, the difference between cholecystectomy and cholecystolithiasis was statistically significant (p<0.000) by chi-square test. Conclusions: In conclusion, cholecystectomy is one of the risk factors of cholangiocarcinoma and the patients who undergo cholecystectomy have a higher risk of cholangiocarcinoma than the control groups. Cholecystectomy should be conducted with caution and the precise surgical treatment of gallbladder diseases is advocated.

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“…Diabetes is considered a risk factor for pancreatic cancer since nearly one-third of patients with pancreatic cancer have a history of diabetes, and diabetic patients have a higher probability of developing pancreatic cancer ( 21 – 23 ). Furthermore, there is also a correlation between hyperglycemia and poor survival in patients with pancreatic cancer, especially among those with type 2 diabetes ( 24 , 25 ).…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Glucose to Lymphocyte Ratio (GLR) as a Prognostic Marker for Patients With Pancreatic Cancer

et al. 2020

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Glucose metabolism and systemic inflammation have been associated with cancer aggressiveness and patient prognosis in various malignancies. This study aimed to evaluate the prognostic significance of pretreatment GLR(glucose to lymphocyte ratio) and systemic immune inflammation in patients with pancreatic cancer. We studied 360 patients with pathologically diagnosed pancreatic adenocarcinoma that was clinically unresectable. Baseline clinicopathological characteristics and laboratory investigations including fasting blood glucose, platelet count, lymphocyte count, neutrophil count, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA199), and follow-up data were collected for further analysis. The patients were randomly divided into a training cohort (n = 238) and a validation cohort (n = 122). Univariate and multivariate Cox proportional hazard regression analyses were performed to identify the prognostic value of GLR, systemic immune-inflammation markers, and tumor biomarkers. A nomogram model was developed based on the identified prognostic factors, and we used the C-index to evaluate the accuracy of the Cox regression model prediction. Multivariate analysis revealed that GLR [hazard ratio (HR): 2.597; 95% confidence interval (CI): 1.728-3.904)] and CA199 (HR: 2.484; 95% CI: 1.295-4.765) are independent predictors of poor overall survival in the training cohort and were incorporated into the nomogram for OS as independent factors. Moreover, the C-index analyses demonstrated that the C-indexes in the training cohort and the validation cohort were 0.674 and 0.671, respectively. The nomogram model predicts overall survival relatively accurately. We found that the baseline GLR is an independent prognostic factor for patients with pancreatic cancer, and the proposed nomogram can be used as an effective tool for predicting the outcomes of prognosis of patients with pancreatic cancer.

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Angiopoietin-like Protein 2 is a Useful Biomarker for Pancreatic Cancer that is Associated with Type 2 Diabetes Mellitus and Inflammation

Cited by 9 publications

References 26 publications

Dual functions of angiopoietin-like protein 2 signaling in tumor progression and anti-tumor immunity

Dual functions of angiopoietin-like protein 2 signaling in tumor progression and anti-tumor immunity

A Case-Control Study on the Relationship Between Cholecystectomy and Cholangiocarcinoma in China

Clinical Significance of Glucose to Lymphocyte Ratio (GLR) as a Prognostic Marker for Patients With Pancreatic Cancer

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