DOG1 expression is common in human tumors: A tissue microarray study on more than 15,000 tissue samples

Jansen, Kristina; Farahi, Nagina; Büscheck, Franziska; Lennartz, Maximilian; Luebke, Andreas M.; Burandt, Eike; Menz, Anne; Kluth, Martina; Hube‐Magg, Claudia; Hinsch, Andrea; Höflmayer, Doris; Weidemann, Sören; Fraune, Christoph; Möller, Katharina; Lebok, Patrick; Sauter, Guido; Simon, Ronald; Uhlig, Ria; Wilczak, Waldemar; Jacobsen, Frank; Minner, Sarah; Krech, Rainer; Clauditz, Till S.; Bernreuther, Christian; Dum, David; Krech, Till; Marx, Andreas; Steurer, Stefan

doi:10.1016/j.prp.2021.153663

Cited by 14 publications

(14 citation statements)

References 71 publications

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“…After 3 years of continuous follow-up, 37 situations of tumor-free survival, 17 situations of recurrence, and 3 situations of death were found during follow-up. The results confirmed that HPV-16 can be used as an important reference for patient prognosis analysis [ 17 , 18 ].…”

Section: Discussionsupporting

confidence: 64%

HPV-16 Expression and Loss of Cell Differentiation in Primary Bladder Tumors

Pang

Ding

et al. 2022

BioMed Research International

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Objective. Primary bladder tumors have a high degree of malignancy. To investigate the expression of human papillomavirus type 16 (HPV-16) in primary bladder tumors and the loss of cell differentiation and to explore the significance of HPV-16 detection, it is expected to be a disease. Treatment provides a theoretical basis. Methods. Fifty-seven patients with primary bladder tumors admitted to our hospital from January 2019 to January 2022 were selected as the research subjects, and they were divided into HPV-related groups according to the human papillomavirus (HPV) infection status ( n = 28 ) and HPV unrelated group ( n = 29 ). The general data of patients were collected, the expression of HPV-16 in bladder tissue samples was detected, and the correlation between pathological parameters and HPV-16 expression was analyzed. Results. Among HPV subtypes, HPV 16 subtype accounted for the highest proportion, followed by HPV-18 and HPV-6 subtypes; there was no significant difference in tumor stage (stage 1, stage a, stage 2a) between the HPV-related group and the HPV-unrelated group (stage 1, stage a, and stage 2a). P > 0.05 ); there was no significant difference in postoperative pathological expression (high expression and low expression) of patients ( P > 0.05 ); there was no statistical difference in age and gender between HPV-related and HPV-unrelated groups ( P > 0.05 ), HPV-related group and HPV-unrelated group compared daily regular drinking and smoking status, the difference was statistically significant ( P < 0.05 ); HPV-16 expression was not correlated with tumor differentiation degree and age of patients ( P > 0.05 ); the area under the curve (AUC) of HPV-16 for judging primary bladder tumor expression and cellular molecular deletion was 0.891, with a sensitivity of 83.94% and a specificity of 88.57%. Conclusion. HPV-16 is an upper, expressed in primary bladder tumors and will participate in the differentiation and loss of cells, which can provide effective guidance and basis for the diagnosis of primary bladder tumors, which is an important factor for judging the pathological stage and prognosis of patients and can provide a theoretical reference for the formulation of therapeutic measures.

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Section: Discussionsupporting

confidence: 64%

HPV-16 Expression and Loss of Cell Differentiation in Primary Bladder Tumors

Pang

Ding

et al. 2022

BioMed Research International

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“…Cross-reactivities of diagnostically used antibodies are not uncommonly found if an extensive normal tissue screening is executed. For example, we had recently observed non-specific staining of smooth-muscle for the PLAP antibody clone 8A9 27 , spermatocytes of the testis for the DOG1 clone SP31 28 , and of corpus luteum of the ovary, adrenal cortical cells, decidua cells for the SATB2 clone 384R-18 29 .…”

Section: Discussionmentioning

confidence: 99%

Semi-automated validation and quantification of CTLA-4 in 90 different tumor entities using multiple antibodies and artificial intelligence

Dum

Henke

Mandelkow

et al. 2022

Laboratory Investigation

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CTLA-4 is an inhibitory immune checkpoint receptor and a negative regulator of anti-tumor T-cell function. This study is aimed for a comparative analysis of CTLA-4+ cells between different tumor entities. To quantify CTLA-4+ cells, 4582 tumor samples from 90 different tumor entities as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry in a tissue microarray format. Two different antibody clones (MSVA-152R and CAL49) were validated and quantified using a deep learning framework for automated exclusion of unspecific immunostaining. Comparing both CTLA-4 antibodies revealed a clone dependent unspecific staining pattern in adrenal cortical adenoma (63%) for MSVA-152R and in pheochromocytoma (67%) as well as hepatocellular carcinoma (36%) for CAL49. After automated exclusion of non-specific staining reaction (3.6%), a strong correlation was observed for the densities of CTLA-4+ lymphocytes obtained by both antibodies (r = 0.87; p < 0.0001). A high CTLA-4+ cell density was linked to low pT category (p < 0.0001), absent lymph node metastases (p = 0.0354), and PD-L1 expression in tumor cells or inflammatory cells (p < 0.0001 each). A high CTLA-4/CD3-ratio was linked to absent lymph node metastases (p = 0.0295) and to PD-L1 positivity on immune cells (p = 0.0026). Marked differences exist in the number of CTLA-4+ lymphocytes between tumors. Analyzing two independent antibodies by a deep learning framework can facilitate automated quantification of immunohistochemically analyzed target proteins such as CTLA-4.

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“…In the situation that KIT immunostaining or KIT/PDGFRA mutation analysis is defective, DOG1 is widely used as the marker for the diagnosis of GIST ( 9 – 11 ). In addition to GIST, increased expression of DOG1 has been reported in esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), diffuse gastric adenocarcinoma (DGAC), pancreatic adenocarcinoma (PAC), colorectal cancers (CRC) and head and neck squamous cell carcinomas (HNSCC) in recent years ( 12 – 14 ). Moreover, some studies have demonstrated the increased expression of DOG1 in hepatic metastasis from CRC ( 15 ), and others revealed that DOG1 overexpression in HNSCC could be predictive of the presence of distant metastasis ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

DOG1 as a novel antibody-drug conjugate target for the treatment of multiple gastrointestinal tumors and liver metastasis

Chen

et al. 2023

Front. Immunol.

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Discovered On Gastrointestinal stromal tumors protein 1 (DOG1), a major calcium-activated chloride channel, has been used as a common diagnostic marker for gastrointestinal stromal tumors. However, the therapeutic application of DOG1 was not well defined. Here, we aim to investigate its potential as a therapeutic target for an antibody-drug conjugate (ADC) in various cancers of the alimentary tract and metastasis. The DOG1 expression profile was determined among TCGA samples and tissue microarrays. High levels of DOG1 expression were ubiquitously observed in multiple cancer samples from the alimentary tract determined by TCGA samples and tissue microarrays. Circulating tumor cells isolated from metastatic colon cancer patients were also positive for DOG1 expression. The mechanisms of anti-DOG1 antibody were investigated by dual-luciferase reporter assay. The anti-DOG1 antibody could inhibit proliferation and metastasis via p53 signaling in limited cancer cell lines. The anti-DOG1 antibody was conjugated with a microtubule inhibitor DM4, to construct a new anti-DOG1-DM4-ADC to strengthen its activity. The anti-DOG1-DM4-ADC showed cytotoxicity at the nanomolar level in vitro. In the murine xenograft tumor models, treatment of anti-DOG1-DM4-ADC achieved a significant tumor growth inhibition rate. Our study indicates that anti-DOG1-DM4-ADC may be promising therapeutic molecules for DOG1-positive alimentary tract tumors and may be effective in inhibiting recurrence after curative resection of liver metastases of colorectal origin.

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DOG1 expression is common in human tumors: A tissue microarray study on more than 15,000 tissue samples

Cited by 14 publications

References 71 publications

HPV-16 Expression and Loss of Cell Differentiation in Primary Bladder Tumors

HPV-16 Expression and Loss of Cell Differentiation in Primary Bladder Tumors

Semi-automated validation and quantification of CTLA-4 in 90 different tumor entities using multiple antibodies and artificial intelligence

DOG1 as a novel antibody-drug conjugate target for the treatment of multiple gastrointestinal tumors and liver metastasis

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