scholarly journals Gene Expression Profiling for the Diagnosis of Multiple Primary Malignant Tumors

2020 ◽  
Author(s):  
Yu Zheng ◽  
Yifeng Sun ◽  
Yue Kuai ◽  
Guoxiang Fu ◽  
Huimin An ◽  
...  
Keyword(s):  
Gene Expression ◽  
Malignant Tumors ◽  
Clinical Specimen ◽  
Malignant Lesion ◽  
Pathological Diagnosis ◽  
Tumor Type ◽  
Gene Expression Assay ◽  
Significant Difference ◽  
Tumor Origin ◽  
Multiple Primary

Abstract Background: The incidence of multiple primary malignant tumors (MPMTs) is rising due to the development of screening technologies, significant treatment advances and increased aging of the population. For patients with a prior cancer history, identifying the tumor origin of the second malignant lesion has important prognostic and therapeutic implications and still represents a difficult problem in clinical practice. Methods: In this study, we evaluated the performance of a 90-gene expression assay and explored its potential diagnostic utility for MPMTs across a broad spectrum of tumor types. Thirty-five MPMT patients from Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University and Fudan University Shanghai Cancer Center were enrolled; 73 MPMT specimens met all quality control criteria and were analyzed by the 90-gene expression assay. Results: For each clinical specimen, the tumor type predicted by the 90-gene expression assay was compared with its pathological diagnosis, with an overall accuracy of 93.2% (68 of 73, 95% confidence interval: 0.84-0.97). For histopathological subgroup analysis, the 90-gene expression assay achieved an overall accuracy of 95.0% (38 of 40; 95% CI, 0.82-0.99) for well-moderately differentiated tumors and 92.0% (23 of 25; 95% CI, 0.82-0.99) for poorly or undifferentiated tumors, with no statistically significant difference (p-value > 0.5). For squamous cell carcinoma specimens, the overall accuracy of gene expression assay also reached 87.5% (7 of 8; 95% CI, 0.47-0.99) for identifying the tumor origins. Conclusions: The 90-gene expression assay provides flexibility and accuracy in identifying the tumor origin of MPMTs. Future incorporation of the 90-gene expression assay in pathological diagnosis will assist oncologists in applying precise treatments, leading to improved care and outcomes for MPMT patients.

scholarly journals Gene expression profiling for the diagnosis of multiple primary malignant tumors

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yu Zheng ◽  
Yifeng Sun ◽  
Yue Kuai ◽  
Guoxiang Fu ◽  
Huimin An ◽  
...  
Keyword(s):  
Gene Expression ◽  
Malignant Tumors ◽  
Clinical Specimen ◽  
Malignant Lesion ◽  
Pathological Diagnosis ◽  
Tumor Type ◽  
Gene Expression Assay ◽  
Significant Difference ◽  
Tumor Origin ◽  
Multiple Primary

Abstract Background The incidence of multiple primary malignant tumors (MPMTs) is rising due to the development of screening technologies, significant treatment advances and increased aging of the population. For patients with a prior cancer history, identifying the tumor origin of the second malignant lesion has important prognostic and therapeutic implications and still represents a difficult problem in clinical practice. Methods In this study, we evaluated the performance of a 90-gene expression assay and explored its potential diagnostic utility for MPMTs across a broad spectrum of tumor types. Thirty-five MPMT patients from Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University and Fudan University Shanghai Cancer Center were enrolled; 73 MPMT specimens met all quality control criteria and were analyzed by the 90-gene expression assay. Results For each clinical specimen, the tumor type predicted by the 90-gene expression assay was compared with its pathological diagnosis, with an overall accuracy of 93.2% (68 of 73, 95% confidence interval 0.84–0.97). For histopathological subgroup analysis, the 90-gene expression assay achieved an overall accuracy of 95.0% (38 of 40; 95% CI 0.82–0.99) for well-moderately differentiated tumors and 92.0% (23 of 25; 95% CI 0.82–0.99) for poorly or undifferentiated tumors, with no statistically significant difference (p-value > 0.5). For squamous cell carcinoma specimens, the overall accuracy of gene expression assay also reached 87.5% (7 of 8; 95% CI 0.47–0.99) for identifying the tumor origins. Conclusions The 90-gene expression assay provides flexibility and accuracy in identifying the tumor origin of MPMTs. Future incorporation of the 90-gene expression assay in pathological diagnosis will assist oncologists in applying precise treatments, leading to improved care and outcomes for MPMT patients.

scholarly journals Gene Expression Profiling For Diagnosis of Multiple Primary Malignant Tumors

2020 ◽  
Author(s):  
Yu Zheng ◽  
Yifeng Sun ◽  
Yue Kuai ◽  
Guoxiang Fu ◽  
Huimin An ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Malignant Tumors ◽  
Clinical Specimen ◽  
Tumor Type ◽  
Significant Treatment ◽  
Gene Expression Assay ◽  
Multiple Primary ◽  
Tumor Types

Abstract Background: The incidence of multiple primary malignant tumors (MPMTs) is rising due to the development of screening technologies, significant treatment advances and the increased aging of the population. For patients with a prior cancer history, distinguishing tumor recurrence or metastasis from a second malignant tumor has important prognostic and therapeutic implications and still represents a difficult problem in clinical practice. Methods: In this study, we evaluated the performance of a 90-gene expression assay and explored its potential diagnostic utility for MPMTs across a broad spectrum of tumor types. Twenty-four MPMT patients from Sir Run Run Shaw Hospital, college of medicine, Zhejiang University were enrolled in this study. A total of 51 MPMT specimens met all quality control criteria and were analyzed by the 90-gene expression assay. Results: For each clinical specimen, the tumor type predicted by the 90-gene expression assay was compared with its reference diagnosis with an overall accuracy of 94.1% (48 of 51, 95% confidence interval: 0.83-0.98). Additionally, the hierarchical clustering of 90-gene expression profiling in 51 specimens revealed MPMT samples were grouped together depending on tumor types or system types rather than individual MPMT patients. Conclusions: Therefore, the 90-gene expression assay provides flexibility and accuracy in identifying the tissue origin of MPMTs, especially in squamous cell carcinoma. Future incorporation of the 90-gene expression assay in the pathological diagnosis will assist oncologists in applying precise treatments, leading to improved care and outcomes for MPMT patients.

scholarly journals Ovarian tumors: Incidence, histological type of lesions and treatment in pediatric age group

2021 ◽  
Vol 75 ◽  
pp. 292-296
Author(s):  
Patrycja Sosnowska-Sienkiewicz ◽  
Piotr Nogal ◽  
Dawid Gawron ◽  
Korneliusz Wójcik ◽  
Danuta Januszkiewicz-Lewandowska ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Malignant Tumors ◽  
Histopathological Examination ◽  
Tumor Staging ◽  
Benign Lesion ◽  
Mature Teratoma ◽  
Malignant Lesion ◽  
Ovarian Tumors ◽  
Histological Type ◽  
Tumor Type

Background: The aim of this study was to evaluate the incidence and histological type of lesions affecting the ovaries and to analyze employed methods of invasive treatment. Materials&Methods: Medical records of patients who were treated surgically for ovarian tumors in the years 2015 -2019 were reviewed. The study group was comprised of 31 female patients. Results: During 5 years time, there were 31 girls in the age from 3 months to 17 years hospitalized in the department. The mean age was 11 years. Histopathological examination was performed in all of these cases. 12 patients were diagnosed with malignant lesion, 19 with benign lesion. The most commonly diagnosed malignant tumors were a dysgerminoma and a mixed germ cell tumor. In the group of benign lesions, the most frequent tumor type was mature teratoma. The first occurring symptom was abdominal pain. Some of the lesions were diagnosed accidentally during ultrasonography. The diagnostics was expanded depending on the size of the tumor, staging and clinical condition of the patient. All the patients were treated surgically, 16 of them underwent laparoscopic surgery. Torsion of the ovary or oviduct was observed in 3 cases. Chemotherapy was introduced in 8 cases as complementary treatment. Conclusions: The most commonly diagnosed tumor was mature teratoma. Ultrasonography is the most frequent method of the ovaries’ examination. Ovarian lesions are characterized by non-specific clinical symptoms, which is associated with prevalent incidental detection during ultrasonography.

scholarly journals 90-Gene Expression Profiling for Tissue Origin Diagnosis of Cancer of Unknown Primary

2021 ◽  
Vol 11 ◽  
Author(s):  
Yi Zhang ◽  
Lei Xia ◽  
Dawei Ma ◽  
Jing Wu ◽  
Xinyu Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Malignant Tumors ◽  
Expression Profiles ◽  
Cancer Of Unknown Primary ◽  
The Cancer Genome Atlas ◽  
Unknown Primary ◽  
Gene Expression Assay ◽  
Primary Location ◽  
Cancer Genome Atlas ◽  
Expression Characteristics

Cancer of unknown primary (CUP), in which metastatic diseases exist without an identifiable primary location, accounts for about 3–5% of all cancer diagnoses. Successful diagnosis and treatment of such patients are difficult. This study aimed to assess the expression characteristics of 90 genes as a method of identifying the primary site from CUP samples. We validated a 90-gene expression assay and explored its potential diagnostic utility in 44 patients at Jiangsu Cancer Hospital. For each specimen, the expression of 90 tumor-specific genes in malignant tumors was analyzed, and similarity scores were obtained. The types of malignant tumors predicted were compared with the reference diagnosis to calculate the accuracy. In addition, we verified the consistency of the expression profiles of the 90 genes in CUP secondary malignancies and metastatic malignancies in The Cancer Genome Atlas. We also reported a detailed description of the next-generation coding sequences for CUP patients. For each clinical medical specimen collected, the type of malignant tumor predicted and analyzed by the 90-gene expression assay was compared with its reference diagnosis, and the overall accuracy was 95.4%. In addition, the 90-gene expression profile generally accurately classified CUP into the cluster of its primary tumor. Sequencing of the exome transcriptome containing 556 high-frequency gene mutation oncogenes was not significantly related to the 90 genes analysis. Our results demonstrate that the expression characteristics of these 90 genes can be used as a powerful tool to accurately identify the primary sites of CUP. In the future, the inclusion of the 90-gene expression assay in pathological diagnosis will help oncologists use precise treatments, thereby improving the care and outcomes of CUP patients.

Real-Time PCR Gene Expression Profiling of Microarray Gene Signatures in Acute Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4401-4401
Author(s):  
Ebrahim Sakhinia ◽  
Mahboubeh Farahangpour ◽  
John A. Liu Yin ◽  
Gerard Brady ◽  
Judith A. Hoyland ◽  
...  
Keyword(s):  
Gene Expression ◽  
Real Time ◽  
Real Time Pcr ◽  
Cyclin D3 ◽  
Expression Level ◽  
Tumor Type ◽  
Gene Signatures ◽  
Significant Difference ◽  
The Mean ◽  
Microarray Gene

Abstract Cancer subtype discovery and classification using microarray gene signatures has the potential to transform pathological diagnosis but measurement of indicator genes in routine practice remains difficult. We tested use of real-time PCR measurement of indicator genes for AML and ALL (Golub et al, Science, 1999) as a method for validation and application of microarray gene signatures. Mononuclear cells (MC) were isolated from whole bone marrow (BM) aspirates by density gradient centrifugation and sorted into unselected (total), CD34+ve and CD34-ve fractions. The mRNA in each fraction was globally amplified using a PolyA PCR method. We measured the expression profile of the 17 top ranked genes (cystatin C, leptin receptor, fumarylacetoacetate, CD33, HoxA9, adipsin, proteoglycan 1, LTC4 synthase, LYN, C-myb, MB-1, cyclin D3, SNF2, RbAp48, proteasome iota, HkrT-1 and E2A) from Golub et al (1999) by real-time PCR. All values were calibrated against control standards and normalized to the mean of three housekeeping genes (IF2-beta, GAPDH and human ribosomal protein S9). Data for all 17 genes were obtained for 4 (ALL), 26 (AML), 12 (AML remission) and 9 (morphologically normal) BM samples, each fractionated into three fractions (total MC, CD34+ve MC & CD34−ve MC). There was no significant difference in the mean of three housekeeping gene expression levels between the diagnostic groups. Comparison of the expression level of the other genes confirmed ability to separate AML and ALL, whilst the direction of expression change (increased or decreased) for each gene between AML and ALL was the same as found by Golub et al. In particular, c-myb showed largest significant increase in ALL vs AML in the total BM fraction, whilst cystain c was increased in AML in the CD34−ve fraction. hSNF2b was significantly increased in the ALL total B.M fraction and Hox-A9 was significantly increased in the AML CD34+ve B.M fraction. Furthermore expression level of LYN and CD33 was significantly increased in AML compared to remission AML, indicating ability of the method to determine activity status of disease. In addition, several of the genes provided better separation between AML and ALL when measured in the CD34+ve and −ve fractions indicating more prominent expression in cells of different maturity and that prior fractionation is diagnostically more informative. The results demonstrate ability of the method to validate gene expression signatures by an independent method, which is simple, sensitive and robust, allowing translation to routine clinical use. Whilst the present study used AML and ALL, in principle the method could be extended to any other tumor type for which gene signatures exist.

Identification of cancer of unknown primary with gene expression profiling

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10052-10052
Author(s):  
H. Li ◽  
K. Qu ◽  
K. Tokoro ◽  
Y. Ren ◽  
J. Y. Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Real Time Pcr ◽  
Expression Profiling ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cancer Of Unknown Primary ◽  
Unknown Primary ◽  
Tumor Type ◽  
Tumor Origin ◽  
Tumor Types

10052 Background: Patients with metastatic cancer of unknown primary (CUP) generally have a poor prognosis, with a median survival of 2–10 months. Conventional diagnostic approaches for identifying the primary tumor site are successful in only 20%-30% of cases; however, such identification provides prognostic information and helps with selection of tumor-specific therapy, leading to improved survival. Recent studies indicate that gene expression-based classification of CUP is highly successful in predicting the site of origin. We report herein development and validation of a method that determines the site of tumor origin by comparing the gene expression profiles of CUP cases to those in a database created from known tumor types. Methods: RNA extracted from frozen and formalin-fixed, paraffin-embedded (FFPE) tissue wasis purified and amplified using the Paradise Reagent System System (Arcturus, Mountain View, CA). Following reverse-transcription, cDNA products wereare used in a semi-quantitative real-time PCR to detect 87 tumor-associated genes and 5 reference genes in an ABI PRISM 7900HT Detection System (Applied Biosystems, Foster City, CA). Gene expression data wereare then compared to those in a database, composed of gene expression profiles of 571 samples from 39 different tumor types, using k-nearest neighbor analysis to predict the most likely site of tumor origin. Intra- and interassay reproducibility was determined. Frozen and FFPE tissues (n=57) from a well-characterized, independent sample set were also tested in a blinded manner to further validate the method. Results: Based on the real-time PCR cycle threshold, the intra- and interassay reproducibility ranged from 0.1%-4.3% and 0.5%-8.2%, respectively. The primary tumor type was identified in 77% of cases. The assay determined the correct tumor type in 88% (44/50) of the samples. Seven samples were not reported: 3 failed to amplify adequately and 4 had an unacceptably low confidence level. Conclusions: We have shown that gene expression profiling can determine the most likely site of tumor origin. Our data suggest that this new method is able tomay identify the primary site of tumor origin in 77% of CUP cases. No significant financial relationships to disclose.

scholarly journals Expression of Phosphofructokinase-1 Gene in Streptozotocinized Diabetic Rats Fed Fermented and Non-Fermented Maize Diets

2021 ◽  
pp. 149-164
Author(s):  
Chukwudi Nze ◽  
Osaretin Albert Taiwo Ebuehi
Keyword(s):  
Gene Expression ◽  
Lipid Profile ◽  
Blood Chemistry ◽  
Diabetic Control ◽  
Diabetic Rats ◽  
Antioxidant Assay ◽  
Gene Expression Assay ◽  
Significant Difference ◽  
The Impact

Aim: This nutrigenomic research study is to investigate the impact of fermented maize (FM) and non-fermented maize (N-FM) diets on the expression of phosphofructokinase-1 (PFK-1) gene in a diabetic state. Methodology: The rats were equally grouped into four for the subsequent two weeks after acclimatization; Group 1 contained streptozotocinized-diabetic rats fed with FM diet (DFM), Group 2 contained streptozotocinized-diabetic rats fed with N-FM diet (DNM), Group 3 contained the normal control rats fed with standard rodent chow (NCG) and Group 4 contained diabetic control rats fed with standard rodent chow (DCG). The total phenol, flavonoid and antioxidant capacity (in vitro) of the maize diets were analyzed. Results: Rats fed the N-FM diet had higher concentration of phenols (73.20±0.9 mg/100 g) and flavonoids (82.83±1.02 mg/100 g). The in vitro antioxidant assay showed a statistically significant difference between the FM and N-FM diets (p<0.05). After the two weeks period, animals were sacrificed and blood samples obtained for blood chemistry and lipid profile tests. The livers were harvested for antioxidant activity and gene expression assay. The antioxidant assay showed no statistically significant difference among all groups, as well as the blood chemistry and lipid profile. The gene expression assay carried out using two-step Real-time qPCR, showed that PFK-1 gene was more expressed in the DFM group when compared to the DNM and DCG groups. Conclusion: The FM diet enhanced the expression of PFK-1 gene in streptozotocinized-diabetic rats.

ATF4, DLX3, FRA1, MSX2, C/EBP-ζ, and C/EBP-α Shape the Molecular Basis of Therapeutic Effects of Zoledronic Acid in Bone Disorders

2020 ◽  
Vol 20 (18) ◽  
pp. 2274-2284
Author(s):  
Faroogh Marofi ◽  
Jalal Choupani ◽  
Saeed Solali ◽  
Ghasem Vahedi ◽  
Ali Hassanzadeh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Zoledronic Acid ◽  
Mrna Expression ◽  
Promoter Methylation ◽  
Methylation Level ◽  
Target Genes ◽  
Osteoblastic Differentiation ◽  
Therapeutic Effects ◽  
Significant Difference ◽  
Scheduled Time

Objective: Zoledronic Acid (ZA) is one of the common treatment choices used in various boneassociated conditions. Also, many studies have investigated the effect of ZA on Osteoblastic-Differentiation (OSD) of Mesenchymal Stem Cells (MSCs), but its clear molecular mechanism(s) has remained to be understood. It seems that the methylation of the promoter region of key genes might be an important factor involved in the regulation of genes responsible for OSD. The present study aimed to evaluate the changes in the mRNA expression and promoter methylation of central Transcription Factors (TFs) during OSD of MSCs under treatment with ZA. Materials and Methods: MSCs were induced to be differentiated into the osteoblastic cell lineage using routine protocols. MSCs received ZA during OSD and then the methylation and mRNA expression levels of target genes were measured by Methylation Specific-quantitative Polymerase Chain Reaction (MS-qPCR) and real.time PCR, respectively. The osteoblastic differentiation was confirmed by Alizarin Red Staining and the related markers to this stage. Results: Gene expression and promoter methylation level for DLX3, FRA1, ATF4, MSX2, C/EBPζ, and C/EBPa were up or down-regulated in both ZA-treated and untreated cells during the osteodifferentiation process on days 0 to 21. ATF4, DLX3, and FRA1 genes were significantly up-regulated during the OSD processes, while the result for MSX2, C/EBPζ, and C/EBPa was reverse. On the other hand, ATF4 and DLX3 methylation levels gradually reduced in both ZA-treated and untreated cells during the osteodifferentiation process on days 0 to 21, while the pattern was increasing for MSX2 and C/EBPa. The methylation pattern of C/EBPζ was upward in untreated groups while it had a downward pattern in ZA-treated groups at the same scheduled time. The result for FRA1 was not significant in both groups at the same scheduled time (days 0-21). Conclusion: The results indicated that promoter-hypomethylation of ATF4, DLX3, and FRA1 genes might be one of the mechanism(s) controlling their gene expression. Moreover, we found that promoter-hypermethylation led to the down-regulation of MSX2, C/EBP-ζ and C/EBP-α. The results implicate that ATF4, DLX3 and FRA1 may act as inducers of OSD while MSX2, C/EBP-ζ and C/EBP-α could act as the inhibitor ones. We also determined that promoter-methylation is an important process in the regulation of OSD. However, yet there was no significant difference in the promoter-methylation level of selected TFs in ZA-treated and control cells, a methylation- independent pathway might be involved in the regulation of target genes during OSD of MSCs.

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