Peritumoral plasmacytoid dendritic cells predict a poor prognosis for intrahepatic cholangiocarcinoma after curative resection

Abstract Background: Plasmacytoid dendritic cells (pDCs) are present in various primary and metastatic human neoplasms; however, their clinical significance in intrahepatic cholangiocarcinoma is not clear. Methods: To evaluate pDCs’ distributions in and around tumors as well as their potential function and predictive value for prognosis in patients undergoing curative resection, we performed immunohistochemistry to examine the expression of pDC marker BDCA2, and CD3, CD4, CD8 and Foxp3 in intratumoral and peritumoral tissues from 359 patients with intrahepatic cholangiocarcinoma and compared with prognostic and clinicopathologic factors. Results: Results showed that patients with high numbers of BDCA2+ pDCs in peritumoral tissues were more likely to have elevated levels of carbohydrate antigen 19-9 and gamma-glutamyl transferase, larger and more tumors, advanced tumor-node-metastasis staging, more vascular/bile duct invasion, and lymphatic metastasis in association with greater chance of recurrence and shorter overall survival. Peritumoral tissues with larger numbers of pDCs also showed increased Foxp3+ regulatory T cell infiltration, both of which were found to be independent factors for predicting time to recurrence and overall survival. By contrast, patient outcomes were not associated with the presence of intratumoral pDCs. Conclusions: Peritumoral pDC infiltration may indicate an immune tolerogenic peritumor microenvironment and can be used to predict a poor prognosis for patients undergoing curative resection for intrahepatic cholangiocarcinoma.

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Peritumoral Plasmacytoid Dendritic Cells Predict a Poor Prognosis for Intrahepatic Cholangiocarcinoma After Curative Resection

10.21203/rs.3.rs-60882/v1 ◽

2020 ◽

Author(s):

Zhi-Qiang Hu ◽

Zheng-Jun Zhou ◽

Chu-Bin Luo ◽

Hao-Yang Xin ◽

Jia Li ◽

...

Keyword(s):

Overall Survival ◽

Dendritic Cells ◽

Intrahepatic Cholangiocarcinoma ◽

Poor Prognosis ◽

Curative Resection ◽

Carbohydrate Antigen ◽

Plasmacytoid Dendritic Cells ◽

Gamma Glutamyl Transferase ◽

Advanced Tumor ◽

Glutamyl Transferase

Abstract Background Plasmacytoid dendritic cells (pDCs) are present in various primary and metastatic human neoplasms; however, their clinical significance in intrahepatic cholangiocarcinoma is not clear. Methods To evaluate pDCs’ distributions in and around tumors as well as their potential function and predictive value for prognosis in patients undergoing curative resection, we performed immunohistochemistry to examine the expression of pDC marker BDCA2, and CD3, CD4, CD8 and Foxp3 in intratumoral and peritumoral tissues from 359 patients with intrahepatic cholangiocarcinoma and compared with prognostic and clinicopathologic factors. Results Results showed that patients with high numbers of BDCA2+ pDCs in peritumoral tissues were more likely to have elevated levels of carbohydrate antigen 19 − 9 and gamma-glutamyl transferase, larger and more tumors, advanced tumor-node-metastasis staging, more vascular/bile duct invasion, and lymphatic metastasis in association with greater chance of recurrence and shorter overall survival. Peritumoral tissues with larger numbers of pDCs also showed increased Foxp3+ regulatory T cell infiltration, both of which were found to be independent factors for predicting time to recurrence and overall survival. By contrast, patient outcomes were not associated with the presence of intratumoral pDCs. Conclusions Peritumoral pDC infiltration may indicate an immune tolerogenic peritumor microenvironment and can be used to predict a poor prognosis for patients undergoing curative resection for intrahepatic cholangiocarcinoma.

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Peritumoral plasmacytoid dendritic cells predict a poor prognosis for intrahepatic cholangiocarcinoma after curative resection

10.21203/rs.3.rs-60882/v3 ◽

2020 ◽

Author(s):

Zhi-Qiang Hu ◽

Zheng-Jun Zhou ◽

Chu-Bin Luo ◽

Hao-Yang Xin ◽

Jia Li ◽

...

Keyword(s):

Overall Survival ◽

Dendritic Cells ◽

Intrahepatic Cholangiocarcinoma ◽

Poor Prognosis ◽

Curative Resection ◽

Carbohydrate Antigen ◽

Plasmacytoid Dendritic Cells ◽

Gamma Glutamyl Transferase ◽

Advanced Tumor ◽

Glutamyl Transferase

Abstract Background: Plasmacytoid dendritic cells (pDCs) are present in various primary and metastatic human neoplasms; however, their clinical significance in intrahepatic cholangiocarcinoma is not clear. Methods: To evaluate pDCs’ distributions in and around tumors as well as their potential function and predictive value for prognosis in patients undergoing curative resection, we performed immunohistochemistry to examine the expression of pDC marker BDCA2, and CD3, CD4, CD8 and Foxp3 in intratumoral and peritumoral tissues from 359 patients with intrahepatic cholangiocarcinoma and compared with prognostic and clinicopathologic factors. Results: Results showed that patients with high numbers of BDCA2+ pDCs in peritumoral tissues were more likely to have elevated levels of carbohydrate antigen 19-9 and gamma-glutamyl transferase, larger and more tumors, advanced tumor-node-metastasis staging, more vascular/bile duct invasion, and lymphatic metastasis in association with greater chance of recurrence and shorter overall survival. Peritumoral tissues with larger numbers of pDCs also showed increased Foxp3+ regulatory T cell infiltration, both of which were found to be independent factors for predicting time to recurrence and overall survival. By contrast, patient outcomes were not associated with the presence of intratumoral pDCs. Conclusions: Peritumoral pDC infiltration may indicate an immune tolerogenic peritumor microenvironment and can be used to predict a poor prognosis for patients undergoing curative resection for intrahepatic cholangiocarcinoma.

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Importance of Normalization of Carbohydrate Antigen 19-9 in Patients With Intrahepatic Cholangiocarcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.780455 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hui Li ◽

Yuan Feng ◽

Chang Liu ◽

Jiawang Li ◽

Jiaxin Li ◽

...

Keyword(s):

Intrahepatic Cholangiocarcinoma ◽

Poor Prognosis ◽

Hazard Function ◽

Curative Resection ◽

Multivariate Analyses ◽

Carbohydrate Antigen ◽

Free Survival ◽

Risk Of Recurrence ◽

Preoperative Serum ◽

Increased Risk

BackgroundAlthough carbohydrate antigen 19-9 (CA19-9) is an established prognostic marker for intrahepatic cholangiocarcinoma (ICC) patients, the significance of elevated preoperative CA19-9 that normalized after resection remains unknown. This study aimed to investigate whether elevated preoperative CA19-9 that normalized after curative resection had an impact on prognosis among patients with ICC.MethodsPatients who underwent curative resection for stage I to III ICC between 2009 and 2018 were identified. Patients were categorized into three cohorts: normal preoperative CA19-9, elevated preoperative CA19-9 but normalized postoperative CA19-9, and persistently elevated postoperative CA19-9. Overall survival (OS), recurrence-free survival (RFS), and hazard function curves over time were analyzed.ResultsA total of 511 patients (247 [48.3%] male; median age, 58 years) were included. Patients with elevated preoperative CA19-9 (n = 378) were associated with worse RFS and OS than those with normal preoperative CA19-9 (n = 152) (both p < 0.001). Patients with persistently elevated postoperative CA19-9 (n = 254) were correlated with lower RFS and OS than the combined cohorts with normal postoperative CA19-9 (n = 257) (both p < 0.001). The hazard function curves revealed that the risk of recurrence and mortality peaked earlier and higher in the elevated postoperative CA19-9 group than the other 2 groups. Multivariate analyses identified persistently elevated, rather than normalized, postoperative CA19-9 as an independent risk factor for shorter RFS and OS in ICC.ConclusionsElevated preoperative serum CA19-9 that normalizes after curative resection is not an indicator of poor prognosis in ICC. Patients with persistently elevated postoperative CA19-9 are at increased risk of recurrence and death.

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Prognostic nomogram for predicting 5-year overall survival in Chinese patients with high-grade osteosarcoma

Scientific Reports ◽

10.1038/s41598-021-97090-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Zhihong Yao ◽

Zunxian Tan ◽

Jifei Yang ◽

Yihao Yang ◽

Cao Wang ◽

...

Keyword(s):

Overall Survival ◽

Calibration Curve ◽

Curve Analysis ◽

Cox Proportional Hazards Model ◽

Chinese Patients ◽

Gamma Glutamyl Transferase ◽

High Grade ◽

Decision Curve Analysis ◽

High Grade Osteosarcoma ◽

Glutamyl Transferase

AbstractThis study aimed to construct a widely accepted prognostic nomogram in Chinese high-grade osteosarcoma (HOS) patients aged ≤ 30 years to provide insight into predicting 5-year overall survival (OS). Data from 503 consecutive HOS patients at our centre between 12/2012 and 05/2019 were retrospectively collected. Eighty-four clinical features and routine laboratory haematological and biochemical testing indicators of each patient at the time of diagnosis were collected. A prognostic nomogram model for predicting OS was constructed based on the Cox proportional hazards model. The performance was assessed by the concordance index (C-index), receiver operating characteristic curve and calibration curve. The utility was evaluated by decision curve analysis. The 5-year OS was 52.1% and 2.6% for the nonmetastatic and metastatic patients, respectively. The nomogram included nine important variables based on a multivariate analysis: tumour stage, surgical type, metastasis, preoperative neoadjuvant chemotherapy cycle, postoperative metastasis time, mean corpuscular volume, tumour-specific growth factor, gamma-glutamyl transferase and creatinine. The calibration curve showed that the nomogram was able to predict 5-year OS accurately. The C-index of the nomogram for OS prediction was 0.795 (range, 0.703–0.887). Moreover, the decision curve analysis curve also demonstrated the clinical benefit of this model. The nomogram provides an individualized risk estimate of the 5-year OS in patients with HOS aged ≤ 30 years in a Chinese population-based cohort.

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Peer review report 1 on “Serum gamma-glutamyl transferase levels affect the prognosis of patients with intrahepatic cholangiocarcinoma who receive postoperative adjuvant transcatheter arterial chemoembolization: A propensity score matching study”

International Journal of Surgery ◽

10.1016/j.ijsu.2016.12.062 ◽

2017 ◽

Vol 37 ◽

pp. 42

Author(s):

Imtiaz A. Wani

Keyword(s):

Propensity Score ◽

Peer Review ◽

Propensity Score Matching ◽

Intrahepatic Cholangiocarcinoma ◽

Transcatheter Arterial Chemoembolization ◽

Gamma Glutamyl Transferase ◽

Gamma Glutamyl ◽

Glutamyl Transferase ◽

Arterial Chemoembolization

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Intratumoral neutrophils and plasmacytoid dendritic cells indicate poor prognosis and are associated with pSTAT3 expression in AJCC stage I/II melanoma

Cancer ◽

10.1002/cncr.26511 ◽

2011 ◽

Vol 118 (9) ◽

pp. 2476-2485 ◽

Cited By ~ 134

Author(s):

Trine O. Jensen ◽

Henrik Schmidt ◽

Holger J. Møller ◽

Frede Donskov ◽

Morten Høyer ◽

...

Keyword(s):

Dendritic Cells ◽

Poor Prognosis ◽

Plasmacytoid Dendritic Cells ◽

Stage I ◽

Ajcc Stage

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ZEB1 expression is associated with prognosis of intrahepatic cholangiocarcinoma

Journal of Clinical Pathology ◽

10.1136/jclinpath-2015-203115 ◽

2015 ◽

Vol 69 (7) ◽

pp. 593-599 ◽

Cited By ~ 11

Author(s):

Katsumi Terashita ◽

Makoto Chuma ◽

Yutaka Hatanaka ◽

Kanako Hatanaka ◽

Tomoko Mitsuhashi ◽

...

Keyword(s):

Overall Survival ◽

Intrahepatic Cholangiocarcinoma ◽

Poor Prognosis ◽

Prognostic Indicators ◽

Vimentin Expression ◽

Altered Expression ◽

Mesenchymal Transition ◽

Related Proteins ◽

Zeb1 Expression ◽

E Cadherin

Background/AimIntrahepatic cholangiocarcinoma (ICC) is one of the most aggressive malignant tumours, so the identification of molecular targets for ICC is an important issue. Zinc finger E-box binding homeobox 1 (ZEB1) is a key inducer of epithelial–mesenchymal transition (EMT). The aim of the present study was to clarify the clinical significance of ZEB1 in ICC and the associations between ZEB1 expression and EMT-related proteins.MethodsWe immunohistochemically examined the expression of EMT-related proteins, namely ZEB1, vimentin and E-cadherin, in ICC specimens from 102 patients. The clinicopathological and prognostic values of these markers were evaluated.ResultsZEB1 and vimentin were expressed in 46.1% and 43.1% of tumours, respectively, and E-cadherin expression was lost in 44.1% of tumours. ZEB1 expression showed a significant inverse correlation with E-cadherin expression (p=0.004) and a positive correlation with vimentin expression (p=0.022). Altered expression of ZEB1 was associated with aggressive tumour characteristics, including advanced tumour stage (p=0.037), undifferentiated-type histology (p=0.017), lymph node metastasis (p=0.024) and portal vein invasion (p=0.037). Moreover, overall survival rates were significantly lower for patients with high ZEB1 expression than for patients with low ZEB1 expression (p=0.027). Kaplan–Meier analysis also identified E-cadherin expression (p=0.041) and vimentin expression (p=0.049) as prognostic indicators for overall survival.ConclusionsZEB1 expression is associated with tumour progression and poor prognosis in patients with ICC through positive correlations with vimentin and negative correlations with E-cadherin. ZEB1 expression is associated with a poor prognosis and might be an attractive target for the treatment of ICC.

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