scholarly journals Analysis of gastric cancer transcriptome allows the identification of histotype specific molecular signatures with prognostic potential

2021 ◽  
Author(s):  
Adriana Carino ◽  
Luigina Graziosi ◽  
Silvia Marchianò ◽  
Michele Biagioli ◽  
Elisabetta Marino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Intestinal Type ◽  
Diffuse Type ◽  
Rna Seq ◽  
Gastric Cancers ◽  
The Third ◽  
Common Malignancy

AbstractGastric cancer is the fifth most common malignancy but the third leading cause of cancer-associated mortality worldwide. Therapy for gastric cancer remain largely suboptimal making the identification of novel therapeutic targets an urgent medical need. In the present study we have carried out a high-throughput sequencing of transcriptome expression in patients with gastric cancers. Twenty-four patients, among a series of 53, who underwent an attempt of curative surgery for gastric cancers in a single center, were enrolled. Patients were sub-grouped according to their histopathology into diffuse and intestinal types, and the transcriptome of the two subgroups assessed by RNAseq analysis and compared to the normal gastric mucosa. The results of this investigation demonstrated that the two histopathology phenotypes express two different patterns of gene expression. A total of 2064 transcripts were differentially expressed between neoplastic and non neoplastic tissues: 772 were specific for the intestinal type and 407 for the diffuse type. Only 885 transcripts were simultaneously differentially expressed by both tumors. The per pathway analysis demonstrated an enrichment of extracellular matrix and immune dysfunction in the intestinal type including CXCR2, CXCR1, FPR2, CARD14, EFNA2, AQ9, TRIP13, KLK11 and GHRL. At the univariate analysis reduced levels AQP9 was found to be a negative predictor of 4 years survival. In the diffuse type low levels CXCR2 and high levels of CARD14 mRNA were negative predictors of 4 years survival. In summary, we have identified a group of genes differentially regulated in the intestinal and diffuse histo-types of gastric cancers with AQP9, CARD14 and CXCR2 impacting on patients prognosis, although CXCR2 is the only factor independently impacting overall survival.Simple summaryGastric cancer is the fifth most common malignancy and the third leading cause of cancer-associated mortality worldwide. Although several new pharmacological approaches are currently developed, surgery remains the unique valid option of treatment but survival remains very poor over the last decades. Therefore, understanding the underlying molecular mechanisms of the gastric carcinogenesis and identifying sensitive biomarkers could be helpful for the prevention and treatment of the disease. Currently, the high-throughput sequencing techniques, in particular the transcriptomic analysis (RNA-seq) represents a validated technique to obtain a molecular characterization of human cancers. Moreover, it has been established that genetic susceptibility and environmental factors, such as microbial infections may contribute to carcinogenesis. We have characterized the different patterns of gene expression, using RNA-seq analysis and correlated these findings with gastric cancer histological subtypes.

scholarly journals Analysis of Gastric Cancer Transcriptome Allows the Identification of Histotype Specific Molecular Signatures With Prognostic Potential

2021 ◽  
Vol 11 ◽  
Author(s):  
Adriana Carino ◽  
Luigina Graziosi ◽  
Silvia Marchianò ◽  
Michele Biagioli ◽  
Elisabetta Marino ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
High Throughput Sequencing ◽  
Univariate Analysis ◽  
Differentially Expressed ◽  
Intestinal Type ◽  
Diffuse Type ◽  
Curative Surgery ◽  
Gastric Cancers ◽  
Cancer Transcriptome ◽  
Transcriptome Expression

Gastric cancer is the fifth most common malignancy but the third leading cause of cancer-associated mortality worldwide. Therapy for gastric cancer remain largely suboptimal making the identification of novel therapeutic targets an urgent medical need. In the present study we have carried out a high-throughput sequencing of transcriptome expression in patients with gastric cancers. Twenty-four patients, among a series of 53, who underwent an attempt of curative surgery for gastric cancers in a single center, were enrolled. Patients were sub-grouped according to their histopathology into diffuse and intestinal types, and the transcriptome of the two subgroups assessed by RNAseq analysis and compared to the normal gastric mucosa. The results of this investigation demonstrated that the two histopathology phenotypes express two different patterns of gene expression. A total of 2,064 transcripts were differentially expressed between neoplastic and non-neoplastic tissues: 772 were specific for the intestinal type and 407 for the diffuse type. Only 885 transcripts were simultaneously differentially expressed by both tumors. The per pathway analysis demonstrated an enrichment of extracellular matrix and immune dysfunction in the intestinal type including CXCR2, CXCR1, FPR2, CARD14, EFNA2, AQ9, TRIP13, KLK11 and GHRL. At the univariate analysis reduced levels AQP9 was found to be a negative predictor of 4 years survival. In the diffuse type low levels CXCR2 and high levels of CARD14 mRNA were negative predictors of 4 years survival. In summary, we have identified a group of genes differentially regulated in the intestinal and diffuse histotypes of gastric cancers with AQP9, CARD14 and CXCR2 impacting on patients’ prognosis, although CXCR2 is the only factor independently impacting overall survival.

Evaluation of prognostic factors in gene expression and clinicopathologic characteristics in patients with adjuvant chemotherapy for advanced gastric cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 61-61
Author(s):  
M. Azuma ◽  
K. Ishido ◽  
A. Takeuchi ◽  
A. Naruke ◽  
K. Higuchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Prognostic Factor ◽  
Intestinal Type ◽  
Diffuse Type ◽  
Gene Expressions ◽  
Group Iii ◽  
Type Group ◽  
Group I

61 Background: We reported TS expression is an independent prognostic factor in patients with gastric cancer who received postoperative adjuvant chemotherapy with S-1 at 2010 ASCO GI (abstract 32). These pharmacogenomic finding will help for choosing chemotherapeutic agents for personalized therapy in the future. Our aim was to indicate association of TS expression with clinicopathological characteristics in the same patient population. Methods: 39 patients with stage II or III advanced gastric cancer who underwent gastrectomy were analyzed. These patients received adjuvant chemotherapy with S-1 after surgery. Formalin-fixed, paraffin-embedded tumor tissues were dissected by the laser-captured microdissection technique and analyzed for target gene expressions using a quantitative real-time PCR. Results: There were no significant differences between stage II and III in TS gene expressions. TS expression (low ≤ 0.72, high > 0.72) and histological type (intestinal and diffuse) are evaluated for PFS and OS. Patients were classified as Group I (n = 5); low TS and intestinal type, Group II (n = 14); low TS and diffuse type, Group III (n = 13); high TS and diffuse type and Group IV (n = 7); high TS and intestinal type. There were significant differences between these four groups (Kaplan-Meier survival analysis, log-rank test, PFS: p = 0.0112 OS: p = 0.0128). The survival curve showed longer survival both PFS and OS in Groups 1 > 2 > 3 > 4. In low TS situation (responders as Group I and II), there is a trend in patients with intestinal type had a longer survival compared to diffuse type (Group I > II). In high TS situation (non-responders as Group III and IV), the result are opposite, there is a trend in patients with diffuse type had a longer survival compared to Intestinal type (Group III > IV). Conclusions: These data suggest that TS gene expression levels may be molecular markers of prognostic factor for patients with adjuvant chemotherapy for resectable gastric cancer. S-1 might be effect different behavior by both histological type and TS expression. Prospective studies are needed to validate these preliminary findings. No significant financial relationships to disclose.

scholarly journals Pathobiological Characteristics of Intestinal and Diffuse-Type of Gastric Carcinoma-Retrospective Study of Gastric Cancers

2017 ◽  
Vol 6 (2) ◽  
pp. 1462
Author(s):  
M. Priyadharshini ◽  
R. Narmadha ◽  
S. Dhanalakshmi ◽  
Rajesh Natarajan ◽  
S. Subitha ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Retrospective Study ◽  
Gastric Carcinoma ◽  
Nodal Metastasis ◽  
Intestinal Type ◽  
Diffuse Type ◽  
Cell Type ◽  
Gastric Cancers ◽  
Microscopic Features ◽  
Glandular Structures

<p><strong>Background:</strong> Gastric carcinomas have various pathological features. Based on patterns of growth and invasiveness, however, they fall into two types: diffuse type and intestinal type. These two types of carcinoma appear to be different in their histogenetic origins.</p><p><strong>Objectives:</strong> To analyse various types of gastric cancer reported in last five years. To compare the features of intestinal and diffuse type gastric carcinoma including gross appearance, staging, grading of tumor.</p><p><strong>Materials and Methods:</strong> This was a retrospective study of 324 gastric cancer which were surgically resected and received over 5 years. The tumors were divided into groups according to their gross and microscopic patterns. Gross appearance was classified based on Borrmann classification. Microscopic features evaluated include tumor cell type, extent of invasion, degree of maturation, formation of glandular structures, nodal metastasis.</p><p><strong>Results:</strong> Totally 320 cases of gastric cancer were received of which 218(68%) were male, 102(32%) were female. Gastric cancers are rare below the age of 30 years. Comparing the type of gastric cancer intestinal type were 269(84%), diffuse type were 24(7.5%) and other type of gastric cancer including GIST, lymphoma, mucinous adenocarcinoma were 27(8.5%). Younger patients have higher stage of lymph node metastasis in diffuse type, but not for the intestinal type.</p><p><strong>Conclusion:</strong> Gastric cancer more common in male (M:F= 2:1) and most frequently seen in 5th decade. Intestinal type constitutes the most common type of gastric tumor. Gross appearance of diffuse type was predominantly infiltrative (79%).</p>

scholarly journals Comparison of normalization approaches for gene expression studies completed with high-throughput sequencing

PLoS ONE ◽  
2018 ◽  
Vol 13 (10) ◽  
pp. e0206312 ◽  
Author(s):  
Farnoosh Abbas-Aghababazadeh ◽  
Qian Li ◽  
Brooke L. Fridley
Keyword(s):  
Gene Expression ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Expression Studies ◽  
Gene Expression Studies

scholarly journals CDK10 Regulates Gastric Cancer Metastasis By Inhibiting lncRNA-C5ORF42-5 Via Phosphorylation Level of AKT/ERK

2021 ◽  
Author(s):  
Zi-Jian Deng ◽  
Dong-Wen Chen ◽  
Xi-Jie Chen ◽  
Jia-Ming Fang ◽  
Liang Xv ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
High Throughput ◽  
Cancer Metastasis ◽  
High Throughput Sequencing ◽  
Gastric Cancer Cells ◽  
Related Proteins

Abstract Background: Gastric cancer is the fourth most common malignant disease. Both CDK10 and long noncoding RNAs (lncRNAs) have been found to exert biological functions in multiple cancers. However, it is still unclear whether CDK10 represses tumor progression in gastric cancer by reducing potential targeting lncRNAs.Methods: The functions of CDK10 and lncRNA-C5ORF42-5 in proliferation, invasion and migration were assessed by MTS assays, colony formation assays, cell cycle and apoptosis assays, Transwell assays, wound healing assays and animal experiments. We used high-throughput sequencing to confirm the existence of lncRNA-C5ORF42-5 and quantitative real-time PCR was used to evaluate lncRNA expression. Then, with RNA-seq sequencing as well as GO function and KEGG enrichment analysis, we identified the signaling pathways in which lncRNA-C5ORF42-5 was involved in gastric cancer. Finally, western blotting was used to identify the genes regulated by lncRNA-C5ORF42-5.Results: Our results showed that CDK10 is expressed at relatively low levels in gastric cancer cell lines and inhibits the progression of gastric cancer cells both in vitro and in vivo. Next, based on high-throughput sequencing, we identified a novel lncRNA, lncRNA-C5ORF42-5, in the stable CDK10-overexpressing cell line compared with the CDK-knockdown cell line and their controls. Additionally, we confirmed that lncRNA-C5ORF42-5 acts as an oncogene to promote metastasis in gastric cancer in vitro and in vivo. We then ascertained that lncRNA-C5ORF42-5 is a major contributor to the function of CDK10 in gastric cancer metastasis by upregulating lncRNA-C5ORF42-5 to reverse the effects of CDK10 overexpression. Finally, we explored the mechanism by which lncRNA-C5ORF42-5 overexpression affects gastric cancer cells to elucidate whether lncRNA-C5ORF42-5 may increase the activity of the SMAD pathway of BMP signaling and promote the expression of EMT-related proteins, such as E-cadherin. Additionally, overexpression of lncRNA-C5ORF42-5 affected the phosphorylation levels of AKT and ERK.Conclusion: Our findings suggest that CDK10 overexpression represses gastric cancer tumor progression by reducing lncRNA-C5ORF42-5 and hindering activation of the related proteins in metastatic signaling pathways, which provides new insight into developing effective therapeutic strategies in the treatment of metastatic gastric cancer.

scholarly journals Behavior Individuality: A Focus on Drosophila melanogaster

2021 ◽  
Vol 12 ◽  
Author(s):  
Rubén Mollá-Albaladejo ◽  
Juan A. Sánchez-Alcañiz
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Great Effort ◽  
Behavioral Differences ◽  
Adult Behavior ◽  
Large Numbers ◽  
Environmental Variations ◽  
And Function

Among individuals, behavioral differences result from the well-known interplay of nature and nurture. Minute differences in the genetic code can lead to differential gene expression and function, dramatically affecting developmental processes and adult behavior. Environmental factors, epigenetic modifications, and gene expression and function are responsible for generating stochastic behaviors. In the last decade, the advent of high-throughput sequencing has facilitated studying the genetic basis of behavior and individuality. We can now study the genomes of multiple individuals and infer which genetic variations might be responsible for the observed behavior. In addition, the development of high-throughput behavioral paradigms, where multiple isogenic animals can be analyzed in various environmental conditions, has again facilitated the study of the influence of genetic and environmental variations in animal personality. Mainly, Drosophila melanogaster has been the focus of a great effort to understand how inter-individual behavioral differences emerge. The possibility of using large numbers of animals, isogenic populations, and the possibility of modifying neuronal function has made it an ideal model to search for the origins of individuality. In the present review, we will focus on the recent findings that try to shed light on the emergence of individuality with a particular interest in D. melanogaster.

scholarly journals HTSeq - A Python framework to work with high-throughput sequencing data

2014 ◽  
Author(s):  
Simon Anders ◽  
Paul Theodor Pyl ◽  
Wolfgang Huber
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Rapid Development ◽  
Differential Expression Analysis ◽  
Rna Seq ◽  
Sequencing Data ◽  
Standard Work ◽  
Data Formats ◽  
High Throughput Sequencing Data ◽  
Python Package

Motivation: A large choice of tools exists for many standard tasks in the analysis of high-throughput sequencing (HTS) data. However, once a project deviates from standard work flows, custom scripts are needed. Results: We present HTSeq, a Python library to facilitate the rapid development of such scripts. HTSeq offers parsers for many common data formats in HTS projects, as well as classes to represent data such as genomic coordinates, sequences, sequencing reads, alignments, gene model information, variant calls, and provides data structures that allow for querying via genomic coordinates. We also present htseq-count, a tool developed with HTSeq that preprocesses RNA-Seq data for differential expression analysis by counting the overlap of reads with genes. Availability: HTSeq is released as open-source software under the GNU General Public Licence and available from http://www-huber.embl.de/HTSeq or from the Python Package Index, https://pypi.python.org/pypi/HTSeq

scholarly journals Molecular Network Profiling in Intestinal- and Diffuse-Type Gastric Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3833
Author(s):  
Shihori Tanabe ◽  
Sabina Quader ◽  
Ryuichi Ono ◽  
Horacio Cabral ◽  
Kazuhiko Aoyagi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Drug Resistance ◽  
Signaling Pathways ◽  
Pathway Analysis ◽  
Rna Binding ◽  
Binding Protein ◽  
Diffuse Type ◽  
Mesenchymal Transition ◽  
Diffuse Type Gastric Cancer

Epithelial-mesenchymal transition (EMT) plays an important role in the acquisition of cancer stem cell (CSC) feature and drug resistance, which are the main hallmarks of cancer malignancy. Although previous findings have shown that several signaling pathways are activated in cancer progression, the precise mechanism of signaling pathways in EMT and CSCs are not fully understood. In this study, we focused on the intestinal and diffuse-type gastric cancer (GC) and analyzed the gene expression of public RNAseq data to understand the molecular pathway regulation in different subtypes of gastric cancer. Network pathway analysis was performed by Ingenuity Pathway Analysis (IPA). A total of 2815 probe set IDs were significantly different between intestinal- and diffuse-type GC data in cBioPortal Cancer Genomics. Our analysis uncovered 10 genes including male-specific lethal 3 homolog (Drosophila) pseudogene 1 (MSL3P1), CDC28 protein kinase regulatory subunit 1B (CKS1B), DEAD-box helicase 27 (DDX27), golgi to ER traffic protein 4 (GET4), chromosome segregation 1 like (CSE1L), translocase of outer mitochondrial membrane 34 (TOMM34), YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), ribonucleic acid export 1 (RAE1), par-6 family cell polarity regulator beta (PARD6B), and MRG domain binding protein (MRGBP), which have differences in gene expression between intestinal- and diffuse-type GC. A total of 463 direct relationships with three molecules (MYC, NTRK1, UBE2M) were found in the biomarker-filtered network generated by network pathway analysis. The networks and features in intestinal- and diffuse-type GC have been investigated and profiled in bioinformatics. Our results revealed the signaling pathway networks in intestinal- and diffuse-type GC, bringing new light for the elucidation of drug resistance mechanisms in CSCs.

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