Clinical correlation of cadherin‐17 marker with advanced tumor stages and poor prognosis of cholangiocarcinoma

2021 ◽  
Author(s):  
Bo‐Hao Zheng ◽  
Sheng Shen ◽  
Kwong‐Fai Wong ◽  
Zi‐Jun Gong ◽  
Wen‐Tao Sun ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Clinical Correlation ◽  
Advanced Tumor ◽  
Tumor Stages

scholarly journals E-Cadherin expression in human tumors: a tissue microarray study on 10,851 tumors

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Eike Burandt ◽  
Felix Lübbersmeyer ◽  
Natalia Gorbokon ◽  
Franziska Büscheck ◽  
Andreas M. Luebke ◽  
...  
Keyword(s):  
Tissue Microarray ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Lobular Carcinoma ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
Carcinoma Of The Breast ◽  
Advanced Tumor ◽  
Tumor Entities ◽  
E Cadherin

Abstract Background The E-Cadherin gene (CDH1, Cadherin 1), located at 16q22.1 encodes for a calcium-dependent membranous glycoprotein with an important role in cellular adhesion and polarity maintenance. Methods To systematically determine E-Cadherin protein expression in normal and cancerous tissues, 14,637 tumor samples from 112 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry in a tissue microarray format. Results E-Cadherin was strongly expressed in normal epithelial cells of most organs. From 77 tumor entities derived from cell types normally positive for E-Cadherin, 35 (45.5%) retained at least a weak E-Cadherin immunostaining in ≥99% of cases and 61 (79.2%) in ≥90% of cases. Tumors with the highest rates of E-Cadherin loss included Merkel cell carcinoma, anaplastic thyroid carcinoma, lobular carcinoma of the breast, and sarcomatoid and small cell neuroendocrine carcinomas of the urinary bladder. Reduced E-Cadherin expression was linked to higher grade (p = 0.0009), triple negative receptor status (p = 0.0336), and poor prognosis (p = 0.0466) in invasive breast carcinoma of no special type, triple negative receptor status in lobular carcinoma of the breast (p = 0.0454), advanced pT stage (p = 0.0047) and lymph node metastasis in colorectal cancer (p < 0.0001), and was more common in recurrent than in primary prostate cancer (p < 0.0001). Of 29 tumor entities derived from E-Cadherin negative normal tissues, a weak to strong E-Cadherin staining could be detected in at least 10% of cases in 15 different tumor entities (51.7%). Tumors with the highest frequency of E-Cadherin upregulation included various subtypes of testicular germ cell tumors and renal cell carcinomas (RCC). E-Cadherin upregulation was more commonly seen in malignant than in benign soft tissue tumors (p = 0.0104) and was associated with advanced tumor stage (p = 0.0276) and higher grade (p = 0.0035) in clear cell RCC, and linked to advanced tumor stage (p = 0.0424) and poor prognosis in papillary RCC (p ≤ 0.05). Conclusion E-Cadherin is consistently expressed in various epithelial cancers. Down-regulation or loss of E-Cadherin expression in cancers arising from E-Cadherin positive tissues as well as E-Cadherin neo-expression in cancers arising from E-Cadherin negative tissues is linked to cancer progression and may reflect tumor dedifferentiation.

scholarly journals Distribution of tumor-infiltrating-T-lymphocytes and possible tumor-escape mechanisms avoiding immune cell attack in locally advanced adenocarcinomas of the esophagus

2021 ◽  
Author(s):  
M. Schoemmel ◽  
◽  
H. Loeser ◽  
M. Kraemer ◽  
S. Wagener-Ryczek ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Cell ◽  
Locally Advanced ◽  
Tumor Escape ◽  
Inflammatory Microenvironment ◽  
Advanced Tumor ◽  
Tumor Stages ◽  
Tumor Center ◽  
Class 1

Abstract Introduction The inflammatory microenvironment has emerged as one of the focuses of cancer research. Little is known about the immune environment in esophageal adenocarcinoma (EAC) and possible tumor-escape mechanisms to avoid immune cell attack. Patients and methods We measured T cell inflammation (CD3, CD8) in the microenvironment using a standardized software-based evaluation algorithm considering different predefined tumor areas as well as expression of MHC class 1 and PD-L1 on 75 analyzable primarily resected and locally advanced (≥ pT2) EACs. We correlated these findings statistically with clinical data. Results Patients with high amounts of T cell infiltration in their tumor center showed a significant survival benefit of 41.4 months compared to 16.3 months in T cell poor tumors (p = 0.025), although CD3 fails to serve as an independent prognostic marker in multivariate analysis. For the invasion zone, a correlation between number of T-cells and overall survival was not detectable. Loss of MHC1 protein expression on tumor cells was seen in 32% and PD-L1 expression using the combined positive score (CPS) in 21.2%. Most likely due to small numbers of cases, both markers are not prognostically relevant, even though PD-L1 expression correlates with advanced tumor stages. Discussion Our analyses reveal an outstanding, though not statistically independent, prognostic relevance of T-cell-rich inflammation in our group of EACs, in particular driven by the tumor center. For the first time, we describe that the inner part of the invasion zone in EACs shows significantly fewer T-cells than other tumor segments and is prognostically irrelevant. We also demonstrate that the loss of antigen presenting ability via MHC1 downregulation by the carcinoma cells is a common escape mechanism in EACs. Future work will need to show whether tumors with MHC class 1 loss respond less well to immunotherapy.

scholarly journals Colorectal carcinomas with KRAS codon 12 mutation are associated with more advanced tumor stages

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Wenbin Li ◽  
Tian Qiu ◽  
Wenxue Zhi ◽  
Susheng Shi ◽  
Shuangmei Zou ◽  
...  
Keyword(s):  
Colorectal Carcinomas ◽  
Advanced Tumor ◽  
Tumor Stages ◽  
Kras Codon

TREM1 fosters an immunosuppressive tumor microenvironment in papillary thyroid cancer

2021 ◽  
Author(s):  
Yang Zhao ◽  
Cangang Zhang ◽  
Yanan Zhu ◽  
Xi Ding ◽  
Yikun Zhou ◽  
...  
Keyword(s):  
T Cells ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Molecular Mechanisms ◽  
Methylation Status ◽  
Disease Free Survival ◽  
Papillary Thyroid ◽  
Advanced Tumor ◽  
Tumor Stages ◽  
Immunosuppressive Microenvironment

The immunosuppressive microenvironment is associated with poor prognosis in papillary thyroid cancer (PTC); however, the molecular mechanisms involved are unknown. Among triggering receptor expressed on myeloid cell (TREM) family, we found that TREM1 expression in PTC was significantly higher than that in normal tissues. TREM1 overexpression was associated with BRAFV600E profiles and advanced tumor stages. Furthermore, TREM1 mRNA expression was negatively correlated with promoter methylation status. Specifically, hypomethylation of CpG site cg06196379 in the TREM1 promoter was related with poor patient disease free survival (DFS) and a high PTC recurrence rate. Mechanistically, TREM1 was mainly expressed in malignant epithelial cells but not macrophages in PTC by single-cell analysis. PTC tissues with high TREM1 levels had enhanced infiltration of regulatory T cells (Tregs) and decreased infiltration of CD8+ T cells. Our study confirms that hypomethylation-mediated overexpression of TREM1 in PTC cells promotes an immunosuppressive microenvironment by enhancing Treg infiltration. We recommend the future use of therapeutic strategy targeting TREM1 for the treatment of PTC.

scholarly journals MicroRNA-7 as a Potential Biomarker for Prognosis in Pancreatic Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Zhi-qiang Ye ◽  
Chang-lin Zou ◽  
Han-bin Chen ◽  
Ming-jie Jiang ◽  
Zhu Mei ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Progression ◽  
Clinical Significance ◽  
Cancer Progression ◽  
Cox Proportional Hazards Model ◽  
The Cancer Genome Atlas ◽  
Cancer Tissue ◽  
Advanced Tumor ◽  
Potential Biomarker ◽  
Tumor Stages

MicroRNAs play critical roles in tumor progression. Our recent study has indicated that microRNA-7 (miR-7) impairs autophagy-derived pools of glucose to suppress the glycolysis in pancreatic cancer progression. However, the roles of miR-7 in clinical significance and chemoresistance of pancreatic cancer remain unexplored. The aim of this study was to assess the expression of miR-7 in patients with pancreatic cancer and to evaluate the possibility of its usage as a prognostic molecular biomarker. MicroRNA array-based quantification analysis of 372 miRNAs was compared in serum between pancreatic cancer and healthy individuals, gemcitabine-sensitive and gemcitabine-resistance patients. We identified miR-7 showed the potential predictive power for gemcitabine-sensitive patients with pancreatic cancer. Then, the results were validated in pancreatic tissue microarray and The Cancer Genome Atlas (TCGA) dataset, demonstrating that lower miR-7 expression was correlated with more advanced tumor stages and worse prognosis in pancreatic cancer. The Cox proportional-hazards model analysis identified miR-7 to be an independent variable for prediction of the survival. Furthermore, the mechanistic exploration suggested the clinical significance of miR-7 involved its interference effect on autophagy and glycolysis in pancreatic cancer using pancreatic cancer tissue microarrays and TCGA data. Therefore, the results of the present study provide evidences that low microRNA-7 expression may contribute to tumor progression and poor prognosis in pancreatic cancer.

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

2020 ◽  
Vol 20 (1) ◽  
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.

ZEB1-AS1 is associated with poor prognosis in non-small-cell lung cancer and influences cell migration and apoptosis by repressing ID1

2019 ◽  
Vol 133 (2) ◽  
pp. 381-392 ◽  
Author(s):  
Jianjun Jin ◽  
Huanqin Wang ◽  
Jiming Si ◽  
Ran Ni ◽  
Yuanhua Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Poor Prognosis ◽  
Xenograft Model ◽  
Vital Role ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Advanced Tumor

Abstract Long non-coding RNAs (lncRNAs) have been reported to play a vital role in non-small-cell lung cancer (NSCLC). ZEB1-AS1 overexpression predicts a poor prognosis in osteosarcoma and colorectal cancers. In the current study, we determined the clinical significance and prognostic value of ZEB1-AS1 in patients with NSCLC. The expression of ZEB1-AS1 and inhibitor of differentiation-1 (ID1) was measured using qRT-PCR and Western blot. Cell growth, migration, and invasion were determined using colony formation assays, Transwell assay, and flow cytometry, respectively. Tumor growth was determined with a xenograft model. ZEB1-AS1 was significantly up-regulated in NSCLC tissues compared with normal samples. ZEB1-AS1 overexpression was significantly associated with advanced tumor, lymph node, and metastases (TNM) stage and tumor size, as well as poorer overall survival. Moreover, ZEB1-AS1 knockdown inhibited NSCLC cell proliferation and migration, and promoted cell apoptosis. In addition, a chromatin immunoprecipitation assay revealed that ZEB1-AS1 interacted with STAT3, thereby repressing ID1 expression. Furthermore, rescue experiments indicated that ZEB1-AS1 functioned as an oncogene partly by repressing ID1 in NSCLC cells. Taken together, our findings indicate that ZEB1-AS1 serves as a promising therapeutic target to predict the prognosis of NSCLC.

scholarly journals Up-regulated long non-coding RNA ILF3-AS1 indicates poor prognosis of nasopharyngeal carcinoma and promoted cell metastasis

2020 ◽  
Vol 35 (4) ◽  
pp. 61-70
Author(s):  
Xuewen Yang ◽  
Feng Lin ◽  
Feng Gao
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Poor Prognosis ◽  
Tissue Samples ◽  
Small Interference Rna ◽  
Invasion And Migration ◽  
Advanced Tumor ◽  
Bmi1 Expression ◽  
Tumor Node Metastasis Stage ◽  
Novel Target ◽  
And Migration

Background: Long non-coding RNAs (lncRNAs) have been confirmed to participate in the regulation of nasopharyngeal carcinoma. Here, we endeavored to explore the character of lncRNA ILF3-AS1 in the nasopharyngeal carcinoma and its function. Methods: A total of 68 nasopharyngeal carcinoma tissues and adjacent normal nasopharyngeal tissues were collected. Expressions of lncRNA ILF3-AS1 in these tissues were detected using quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between the expression level of lncRNA ILF3-AS1 and clinical pathological characteristics was analyzed. Inhibition of lncRNA ILF3-AS1 was done using small interference RNA. Results: lncRNA ILF3-AS1 expression was significantly up-regulated in the 68 nasopharyngeal carcinoma tissue samples compared to their adjacent normal tissue samples. Increased lncRNA ILF3-AS1 level was related to the advanced tumor node metastasis stage and the metastasis of nasopharyngeal carcinoma. Also, increased lncRNA ILF3-AS1 indicated poor prognosis of nasopharyngeal carcinoma patients. Inhibition of lncRNA ILF3-AS1 reduced proliferation, invasion and migration of nasopharyngeal carcinoma cells. MicroRNA-320a (miR-320a) was determined as a direct target for lncRNA ILF3-AS1 in nasopharyngeal carcinoma. Furthermore, lncRNA ILF3-AS1 could sponge miR-320a to promote BMI1 expression. The expression of BMI1 was significantly inhibited by the down-regulation of lncRNA ILF3-AS1. Conclusions: For the first time, we demonstrated that lncRNA ILF3-AS1 was markedly over-expressed in nasopharyngeal carcinoma tissues and cells. Elevated lncRNA ILF3-AS1 expression was correlated with severe cancer stage and poor prognosis. lncRNA ILF3-AS1 could promote proliferation, invasion, and migration of cells, which might indicate a novel target site for the future diagnosis and therapy of nasopharyngeal carcinoma.

Upregulation of microRNA-203 is associated with advanced tumor progression and poor prognosis in epithelial ovarian cancer

2013 ◽  
Vol 30 (3) ◽  
Author(s):  
Shaosheng Wang ◽  
Xiaohong Zhao ◽  
Jie Wang ◽  
Yingmei Wen ◽  
LinJing Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Tumor Progression ◽  
Poor Prognosis ◽  
Advanced Tumor
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