MicroRNA-based assay for differential diagnosis of mesothelioma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22079-e22079
Author(s):  
H. Benjamin ◽  
D. Lebanony ◽  
S. Tabak ◽  
N. Barabash ◽  
H. Gibori ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Lung Adenocarcinoma ◽  
Tissue Type ◽  
Cancer Tissue ◽  
Diagnostic Assay ◽  
Tissue Samples ◽  
Qrt Pcr ◽  
Primary Lung Adenocarcinoma ◽  
Small Set ◽  
Tumor Types

e22079 Background: Malignant mesothelioma is an aggressive pleural neoplasm, strongly linked to environmental exposures such as asbestos. Mesothelioma can be difficult to differentiate from other tumors in the lung or pleura such as primary lung adenocarcinoma presenting with pleural effusion or metastatic adenocarcinoma from extrathoracic sites. We addressed the increasing need for accurate differential diagnosis of these tumors by developing a diagnostic assay based on expression levels of microRNAs, a family of small, non-coding RNAs whose tissue-specificity has proven applicability for identification of cancer tissue type and histology. Methods: We developed protocols for extraction of high-quality RNA that retain the microRNA fraction from FFPE tissue samples. Microarrays were used for initial profiling. qRT-PCR was used to validate results and to develop a diagnostic assay. Results: We identified microRNAs that are differentially expressed between mesothelioma, lung adenocarcinoma, and other confounding tumor types. A diagnostic assay (miRview™ meso) was developed, that utilizes qRT-PCR measurement of a small set of microRNAs to differentiate between mesothelioma and non-mesothelioma samples. After establishing this profile in more than 30 mesotheliomas and 200 samples of confounding tumors, the microRNA biomarkers were measured using a standardized protocol on a blinded test set. The assay had accuracy greater than 90% in differentiating mesothelioma from other confounding tumor types. More than ¾ of samples were classified with high confidence, and these samples were all correctly identified. Conclusions: MicroRNAs are emerging as effective cancer biomarkers. A robust and simple assay based on the expression level of a few microRNA biomarkers can accurately differentiate mesothelioma from other possible tumors in the lung and pleura. This assay provides an important new tool for diagnosing mesothelioma. [Table: see text]

MicroRNA-based assay for differential diagnosis of squamous from non-squamous non-small cell lung carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11069-11069
Author(s):  
D. Lebanony ◽  
H. Benjamin ◽  
S. Gilad ◽  
K. Ashkenazi ◽  
D. Nonaka ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Cancer Type ◽  
Diagnostic Assay ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Qrt Pcr

11069 Background: Recent advances in biologically directed therapies for non-small cell lung carcinoma (NSCLC) emphasize the need for more accurate sub-classification of NSCLC, as treatment may be dictated by histologic subtype. In particular, squamous histology can be a counter-indication for treatment by VEGF inhibitors. MicroRNAs are highly tissue-specific biomarkers with potential clinical applicability for defining cancer type and origin. MicroRNAs are well preserved in formalin fixed tissue, making them ideal candidates for molecular markers for use in routinely processed material. Here we report on the development and performance of a microRNA-based assay for the differential diagnosis of squamous from non-squamous NSCLC. Methods: We developed protocols for extraction of high-quality RNA that retain the microRNA fraction from FFPE archival tissue samples. MicroRNA microarrays were used to profile more than a hundred NSCLC samples. Specific microRNA qRT-PCR was used to validate results, and to develop a diagnostic assay. Results: We identified a microRNA biomarker that is strongly overexpressed in squamous cell NSCLC. A diagnostic assay (miRview squamous) was developed, that utilizes qRT-PCR measurement of this microRNA, normalized by an additional microRNA and a small nuclear RNA. This assay was validated on a blinded test set of 64 tumor samples, and had sensitivity of 97% and specificity of 91%. More than ¾ of the samples were classified with high confidence, and these classifications were accurate in 96% of the cases. Conclusions: MicroRNAs are becoming an important tool for classification of cancers. A diagnostic assay based on the specificity of a single microRNA accurately identifies squamous from non-squamous NSCLC. This assay provides an important new tool for the classification of NSCLC. [Table: see text]

scholarly journals HOTAIR, HOXC13, and HOXC10 Are Overexpressed in Gastric Cancer

2021 ◽  
Author(s):  
Mahvash Habibi ◽  
Reza Fakhari ◽  
Mina Zamani ◽  
Hamid Galehdari
Keyword(s):  
Gastric Cancer ◽  
Significant Relationship ◽  
Perineural Invasion ◽  
Hox Genes ◽  
Cancer Tissue ◽  
Tissue Samples ◽  
Qrt Pcr ◽  
Genes Expression ◽  
Carcinoma Metastasis ◽  
Positive Correlations

Abstract Gastric cancer is concerned as the second leading cause of tumor-associated death worldwide after lung tumors and is specified as one of the most common malignant cancers. Given the increasing importance of HOX genes in gastric cancer research, this study was aimed at exploring the expression profile of HOTAIR, HOXC13, HOXC10, HOXC13-AS, and HOXC‑AS3 in gastric cancer. To achieve this goal, 30 pairs of tumor and normal margin samples were assessed for these genes expression analyses via qRT-PCR. result we found that, the HOTAIR, HOXC13, and HOXC10 expression was significantly increased in cancer tissue samples in comparison with adjacent normal tissue samples, P<0.01. Moreover, there were significant positive correlations between the expressions of genes studied: HOXC‑AS3 and HOXC10 (r=0.52, P<0.003), HOXC13-AS and HOXC13 (r=0.57, P<0.001), HOTAIR and HOXC‑AS3 (r=0.39, P<0.03), HOTAIR and HOXC13-AS (r=0.36, P<0.05). The HOXC13 and HOXC10 expression exhibited a significant relationship with both distant metastasis and perineural invasion (metastasis: P<0.014, r=0.443 and P<0.0041, r=0.51 perineural invasion: P<0.025, r=0.41 and P<0.0017, r=0.55). The HOXC13-AS displayed a significant relationship with the sex factor so that in females the expression of this gene was higher than males (P<0.030, r=0.4). Our findings suggest that the expression of HOXC genes and HOTAIR lncRNA increased through gastric tumor progression and thus they possibly participate in malignant transformation and gastric carcinoma metastasis.

scholarly journals Identification of a novel prognosis-associated ceRNA network in lung adenocarcinoma via bioinformatics analysis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Yumiao Li ◽  
Xiaoxue Yu ◽  
Yuhao Zhang ◽  
Xiaofang Wang ◽  
Linshan Zhao ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Lines ◽  
Microarray Data ◽  
Messenger Rna ◽  
Target Genes ◽  
Nonsmall Cell Lung Cancer ◽  
The Cancer Genome Atlas ◽  
Tissue Samples ◽  
Qrt Pcr ◽  
Cerna Network

Abstract Background Lung adenocarcinoma (LUAD) is the most common subtype of nonsmall-cell lung cancer (NSCLC) and has a high incidence rate and mortality. The survival of LUAD patients has increased with the development of targeted therapeutics, but the prognosis of these patients is still poor. Long noncoding RNAs (lncRNAs) play an important role in the occurrence and development of LUAD. The purpose of this study was to identify novel abnormally regulated lncRNA–microRNA (miRNA)–messenger RNA (mRNA) competing endogenous RNA (ceRNA) networks that may suggest new therapeutic targets for LUAD or relate to LUAD prognosis. Methods We used the SBC human ceRNA array V1.0 to screen for differentially expressed (DE) lncRNAs and mRNAs in four paired LUAD samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the DE lncRNAs and mRNAs. R bioinformatics packages, The Cancer Genome Atlas (TCGA) LUAD database, and Kaplan–Meier (KM) survival analysis tools were used to validate the microarray data and construct the lncRNA–miRNA–mRNA ceRNA regulatory network. Then, quantitative real-time PCR (qRT-PCR) was used to validate the DE lncRNAs in 7 LUAD cell lines. Results A total of 2819 DE lncRNAs and 2396 DE mRNAs (P < 0.05 and fold change ≥ 2 or ≤ 0.5) were identified in four paired LUAD tissue samples. In total, 255 of the DE lncRNAs were also identified in TCGA. The GO and KEGG analysis results suggested that the DE genes were most enriched in angiogenesis and cell proliferation, and were closely related to human cancers. Moreover, the differential expression of ENST00000609697, ENST00000602992, and NR_024321 was consistent with the microarray data, as determined by qRT-PCR validation in 7 LUAD cell lines; however, only ENST00000609697 was associated with the overall survival of LUAD patients (log-rank P = 0.029). Finally, through analysis of ENST00000609697 target genes, we identified the ENST00000609697–hsa-miR-6791-5p–RASL12 ceRNA network, which may play a tumor-suppressive role in LUAD. Conclusion ENST00000609697 was abnormally expressed in LUAD. Furthermore, downregulation of ENST00000609697 and its target gene RASL12 was associated with poor prognosis in LUAD. The ENST00000609697–hsa-miR-6791-5p–RASL12 axis may play a tumor-suppressive role. These results suggest new potential prognostic and therapeutic biomarkers for LUAD.

scholarly journals The High Expression of PTPRH Is Associated with Poor Prognosis of Human Lung Adenocarcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Aifeng Chen ◽  
Shibiao Ding ◽  
Xiaoqiang Shen ◽  
Xuai Lin
Keyword(s):  
Lung Adenocarcinoma ◽  
Roc Curve ◽  
Immunohistochemical Staining ◽  
Poor Prognosis ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
Disease Stage ◽  
Tissue Samples ◽  
Qrt Pcr ◽  
Kaplan Meier

Objective. The aim of the study is to explore the prognosis value of PTPRH in patients with lung adenocarcinoma (LUAD). Methods. Oncomine, UALCAN, and GEPIA databases were employed to examine the differential expression of PTPRH between LUAD and adjacent tissues. 100 pairs of LUAD and adjacent tissue samples were involved in this study. qRT-PCR and immunohistochemical staining were performed. Meanwhile, we analyzed The Cancer Genome Atlas (TCGA) data to investigate the correlation between PTPRH gene expression and clinicopathological characteristics. Kaplan-Meier analysis and univariate and multivariate Cox analyses were performed to estimate the relationship between PTPRH expression and LUAD prognosis. The evaluation performance was verified by drawing a ROC curve. In addition, through GSEA, the changes of PTPRH expression were analyzed by GSEA to screen out primarily affected signaling pathway. Results. Oncomine, UALCAN, and GEPIA databases showed that the mRNA expression of PTPRH in LUAD tissues was significantly higher than that in adjacent tissues. qRT-PCR and immunohistochemical staining indicated the mRNA and protein levels of PTPRH in LUAD tissues were markedly upregulated. TCGA data showed that the expression of PTPRH was significantly correlated with T stage and disease stage. Kaplan-Meier analysis showed that the patients with high PTPRH expression had a poor prognosis. Univariate and multivariate Cox analyses exhibited that PTPRH expression could act as an independent prognostic factor for LUAD. The ROC curve showed that PTPRH combined with various clinicopathological features could effectively predict the prognosis of LUAD. Finally, GSEA indicated that changes in PTPRH expression level may affect p53, VEGF, Notch, and mTOR cancer-related signaling pathways. Conclusion. Our results demonstrated that PTPRH was highly expressed in LUAD and may be closely correlated with the poor prognosis of LUAD patients.

Abstract #619 Primary Lung Adenocarcinoma in a Sea of Metastatic Thyroid Cancer

2019 ◽  
Vol 25 ◽  
pp. 319-320
Author(s):  
Lourdes Rodriguez ◽  
Mary Baker ◽  
Daniel W Karakla ◽  
David Lieb
Keyword(s):  
Thyroid Cancer ◽  
Lung Adenocarcinoma ◽  
Primary Lung Adenocarcinoma ◽  
Metastatic Thyroid Cancer

Human Chorionic Gonadotropin and CA 15-3 Producing Adenocarcinoma

1998 ◽  
Vol 37 (08) ◽  
pp. 297-298 ◽  
Author(s):  
A. Özet ◽  
A. Arpaci ◽  
S. Kömiircü ◽  
G. Üçkaya
Keyword(s):  
Lung Adenocarcinoma ◽  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Carbohydrate Antigen ◽  
Beta Subunit ◽  
Cancer Antigen ◽  
First Report ◽  
Primary Lung Adenocarcinoma ◽  
Adenocarcinoma Of Lung

Summary50 years old man suffering from primary lung adenocarcinoma presented with high levels of both beta subunit human chorionic gonadotropin (βHCG) and cancer antigen 15-3 (CA 15-3) in the absence of elevated carcinoembrionic antigen (CEA), alfa fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9). Although βHCG or CA 15-3 high levels were reported in adenocarcinoma of lung, this is the first report of a patient with high levels of both markers.

Cellular Localization of Enzymatically Active Thrombin in Intact Human Tissues by Hirudin Binding

1995 ◽  
Vol 73 (05) ◽  
pp. 793-797 ◽  
Author(s):  
Leo R Zacharski ◽  
Vincent A Memoli ◽  
William D Morain ◽  
Jean-Marc Schlaeppi ◽  
Sandra M Rousseau
Keyword(s):  
Tumor Cell ◽  
Cell Carcinoma ◽  
Cellular Localization ◽  
Thrombin Generation ◽  
Normal Lung ◽  
Cancer Tissue ◽  
Immunohistochemical Techniques ◽  
Tumor Types ◽  
Negative Controls

SummaryCellular sites of coagulation activation within complex, intact tissues have been studied by immunohistochemical techniques. Hirudin, a specific and high affinity inihibitor of the active site of thrombin, together with antibody to hirudin were applied to sections of AMeX-fixed specimens of normal lung, kidney, placenta, freshly incised skin and unperturbed skin obtained at fresh autopsy; to rheumatoid synovial tissue; and to malignant tissue from a variety of tumor types. Staining for thrombin was observed selectively on pulmonary alveolar, rheumatoid synovial, and placental macrophages that express an intact extrinsic coagulation pathway. Staining was also observed restricted to the endothelium of capillaries in freshly incised skin but not in either unperturbed skin or in aged incisions. Staining of tumor cell bodies was observed in small cell carcinoma of the lung, renal cell carcinoma, and malignant melanoma tissues that we found previously to show tumor cell-associated procoagulant activity. This staining occurred commonly on cells within the tumor mass that were distant from stromal fibrinogen/fibrin. By contrast, tumor-associated macrophage but not tumor cell staining was seen in adenocarcinoma and squamous cell carcinoma of the lung, and little or no staining was seen in colon cancer tissue. Negative controls in which either the hirudin probe or its antibody were omitted failed to show staining. These results are in accord with previous findings and suggest that such techniques may be useful for studying the cellular sites of thrombin generation in intact tissues. We postulate that administration of potent and specific thrombin antagonists, such as hirudin, to patients with relevant tumor types might be followed by homing of hirudin to tumor cells in vivo so that effects of local thrombin generation on malignant progression can be determined.

A PILOT STUDY OF HER-2/NEU GENE AMPLIFICATION ASSESSED BY FLUORESCENCE IN SITU HYBRIDIZATION (FISH) IN GASTRIC CANCER

2014 ◽  
pp. 15-20
Author(s):  
Van Huy Tran ◽  
Thi Minh Thi Ha ◽  
Trung Nghia Van ◽  
Viet Nhan Nguyen ◽  
Phan Tuong Quynh Le ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Cancer Patients ◽  
Gene Amplification ◽  
Cancer Tissue ◽  
Tissue Samples ◽  
Her 2 ◽  
Gastric Cancer Patients

Background: HER-2/neu is a predictive biomarker for treatment of gastric cancer using trastuzumab in combination with chemotherapy. This study aimed to evaluate the status of HER-2/neu gene amplification using fluorescence in situ hybridization (FISH) in gastric cancer. Patients and methods: thirty six gastric cancer patients were assessed HER-2/neu gene amplification by FISH using PathVysionTM HER-2 DNA Probe kit (including HER-2/neu probe and CEP-17 probe) with biopsy and surgical specimens. Results: The HER-2/neu gene amplification was observed in three cases (8.3%), the HER-2/neu gene amplification rate in Lauren’s intestinal-type and diffuse-type were 11.8% and 5.2%, respectively. Conclusion: We applied successfully FISH technique with gastric cancer tissue samples. This technique could be performed as routine test in gastric cancer in order to select patients that benefit from trastuzumab in combination with chemotherapy.

scholarly journals EP4 as a Negative Prognostic Factor in Patients with Vulvar Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1410
Author(s):  
Anna Buchholz ◽  
Aurelia Vattai ◽  
Sophie Fürst ◽  
Theresa Vilsmaier ◽  
Christina Kuhn ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Vulvar Cancer ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Common Finding ◽  
Cancer Tissue ◽  
Vulvar Carcinoma ◽  
Tissue Samples

New prognostic factors and targeted therapies are urgently needed to improve therapeutic outcomes in vulvar cancer patients and to reduce therapy related morbidity. Previous studies demonstrated the important role of prostaglandin receptors in inflammation and carcinogenesis in a variety of tumor entities. In this study, we aimed to investigate the expression of EP4 in vulvar cancer tissue and its association with clinicopathological data and its prognostic relevance on survival. Immunohistochemistry was performed on tumor specimens of 157 patients with vulvar cancer treated in the Department of Obstetrics and Gynecology, Ludwig-Maximilian-University of Munich, Germany, between 1990 and 2008. The expression of EP4 was analyzed using the well-established semiquantitative immunoreactivity score (IRS) and EP4 expression levels were correlated with clinicopathological data and patients’ survival. To specify the tumor-associated immune cells, immunofluorescence double staining was performed on tissue samples. In vitro experiments including 5-Bromo-2′-Deoxyuridine (BrdU) proliferation assay and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT) viability assay were conducted in order to examine the effect of EP4 antagonist L-161,982 on vulvar carcinoma cells. EP4 expression was a common finding in in the analyzed vulvar cancer tissue. EP4 expression correlated significantly with tumor size and FIGO classification and differed significantly between keratinizing vulvar carcinoma and nonkeratinizing carcinoma. Survival analysis showed a significant correlation of high EP4 expression with poorer overall survival (p = 0.001) and a trending correlation between high EP4 expression and shorter disease-free survival (p = 0.069). Cox regression revealed EP4 as an independent prognostic factor for overall survival when other factors were taken into account. We could show in vitro that EP4 antagonism attenuates both viability and proliferation of vulvar cancer cells. In order to evaluate EP4 as a prognostic marker and possible target for endocrinological therapy, more research is needed on the influence of EP4 in the tumor environment and its impact in vulvar carcinoma.

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