RNA sequencing analyses reveal novel differentially expressed genes and pathways in pancreatic cancer

Mao, Yiming; Shen, Jianjun; Lu, Yue; Lin, Kevin; Wang, Huamin; Li, Yanan; Chang, Ping; Walker, Mary G.; Li, Donghui

doi:10.18632/oncotarget.16451

Cited by 51 publications

(53 citation statements)

References 38 publications

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“…Using TCGA RNA‐seq Level 3 data from four PDAC patients, we found that PAIP2B expression was downregulated in tumors (mean = 90.58) compared to paired normal tissues from the same patient (mean = 150.22) ( p = 0.23, paired t ‐test). This observation agreed with data from our previous RNA‐seq study on paired tumor‐normal tissues of ten PDAC patients, which showed a 7.8‐fold lower expression of PAIP2B in tumors than in normal adjacent tissues ( p = 0.00032) . Notably, the expression of PAIP2B was significantly reduced in tumors compared to that in normal adjacent tissues of other gastrointestinal cancers according to TCGA RNA‐seq data ( p

\leq 8 \times 10^{- 5}

) (Table ).…”

Section: Resultssupporting

confidence: 90%

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Genetic polymorphisms associated with pancreatic cancer survival: a genome‐wide association study

Tang

Wei

Chang

et al. 2017

Intl Journal of Cancer

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Previous findings on the association of genetic factors and pancreatic cancer survival are limited and inconsistent. In a two-stage study, we analyzed the existing genome-wide association study dataset of 868 pancreatic cancer patients from MD Anderson Cancer Center in relation to overall survival using Cox regression. Top hits were selected for replication in another 820 patients from the same institution using the Taqman genotyping method. Functional annotation, pathway analysis, and gene expression analysis were conducted using existing software and databases. We discovered genome-wide significant associations of patient survival with three imputed SNPs which, in complete LD (r2=1), were intronic SNPs of the PAIP2B (rs113988120) and DYSF genes (rs112493246 and rs138529893) located on chromosome 2. The variant alleles were associated with a 3.06-fold higher risk of death (95% confidence interval [CI]=2.10-4.47, P = 6.4 × 10−9) after adjusting for clinical factors. Eleven SNPs were tested in the replication study and the association of rs113988120 with survival was confirmed (HR: 1.57, 95%CI: 1.13-2.20, P = 0.008). In silico analysis found rs1139988120 might lead to altered motif. This locus is in LD (D′=0.77) with 3 eQTL SNPs near or belong to the NAGK and MCEE genes. According to The Cancer Genome Atlas data and our previous RNA-sequencing data, the mRNA expression level of PAIP2B but not NAGK, MCEE or DYSF was significantly lower in pancreatic tumors than in normal adjacent tissues. Additional validation efforts and functional studies are warranted to demonstrate whether PAIP2B is a novel tumor suppressor gene and a potential therapeutic target for pancreatic cancer.

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\leq 8 \times 10^{- 5}

) (Table ).…”

Section: Resultssupporting

confidence: 90%

“…The association of selected SNPs and gene expression levels was evaluated using Genotype‐Tissue Expression (GTEx) and NCBI eQTL database and the RNASeq Level 3 data from TCGA. A previously conducted RNA‐Seq study in paired normal and tumor tissues from ten patients with resected PDAC tumors was also considered.…”

Section: Methodsmentioning

confidence: 99%

Genetic polymorphisms associated with pancreatic cancer survival: a genome‐wide association study

Tang

Wei

Chang

et al. 2017

Intl Journal of Cancer

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“…In contrast, mRNA levels of a number of digestive enzymes appeared to be significantly reduced, such as casein alpha s1 (CSN1S1), perilipin 4 (PLIN4), perilipin 1 (PLIN1), and peptidase M20 domain containing 1 (PM20D1). This finding is consistent with previous observations, which reflect an impairment of exocrine pancreatic functions by the tumor . The majority of DEGs remained a consistent trend of gene expression changes in individual patients.…”

Section: Resultssupporting

confidence: 93%

“…Almost all of these studies used either cell lines or animal models of PC, or microarray‐based methods that have apparent limitations when compared with RNA‐seq techniques. Very recently, a small number of RNA‐seq‐based transcriptome analyses have been conducted to investigate the gene expression profile changes in pancreatic tissues between different groups of patients (eg, tumor vs non‐tumor, short‐survivor vs long‐survivor) . However, those preliminary studies did not fully demonstrate the complex mRNA‐miRNA interaction network and failed to identify genes and molecular mechanisms that may drive the pathogenesis of PC.…”

Section: Introductionmentioning

confidence: 99%

Network‐based integration of mRNA and miRNA profiles reveals new target genes involved in pancreatic cancer

Lin

Liang

et al. 2018

Molecular Carcinogenesis

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Pancreatic cancer is regarded as the most fatal and aggressive malignancy cancer due to its low 5‐year survival rate and poor prognosis. The approaches of early diagnosis and treatment are limited, which makes it urgent to identify the complex mechanism of pancreatic oncogenesis. In this study, we used RNA‐seq to investigate the transcriptomic (mRNA and miRNA) profiles of pancreatic cancer in paired tumor and normal pancreatic samples from ten patients. More than 1000 differentially expressed genes were identified, nearly half of which were also found to be differentially expressed in the majority of examined patients. Functional enrichment analysis revealed that these genes were significantly enriched in multicellular organismal and metabolic process, secretion, mineral transport, and intercellular communication. In addition, only 24 differentially expressed miRNAs were found, all of which have been reported to be associated with pancreatic cancer. Furthermore, an integrated miRNA‐mRNA interaction network was generated using multiple resources. Based on the calculation of disease correlation scores developed here, several genes present in the largest connected subnetwork, such as albumin, ATPase H+/K+ exchanging alpha polypeptide and carcinoembryonic antigen‐related cell adhesion molecule 1, were considered as novel genes that play important roles in the development of pancreatic cancer. Overall, our data provide new insights into further understanding of key molecular mechanisms underlying pancreatic tumorigenesis.

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“…Recently, an RNA sequencing assessment has complemented the list of the previous differently expressed genes in PC tumor samples in comparison to benign pancreatic tissue [34] . These data have been used for PC taxonomy purposes and clinical trial design.…”

Section: Tumor Rna Markersmentioning

confidence: 99%

Genomics in Primary and Secondary Prevention of Pancreatic Cancer

Malats

Molina‐Montes²,

Vecchia³

2017

Public Health Genomics

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Background: Pancreatic cancer (PC) is one of the deadliest cancers worldwide for which little clinical progress has been made in the last decades. Furthermore, increased trends of PC mortality rates have been reported in Westernised countries. PC is usually diagnosed in advanced stages, precluding patients of an effective treatment. Identifying high-risk populations and early detection markers is the first and crucial step to impact on these figures and change the PC horizon. Aims/Objectives: To discuss the published body of evidence on host and tumor genomics promising markers for primary and/or secondary personalised PC prevention, as well as the future perspectives in the field. Methods: A review of the literature was performed to identify germline and tumor DNA and RNA markers that showed potential usefulness in defining the high-risk population, diagnosing the disease early, and identifying new carcinogens associated with PC. Results: Only high-penetrance inherited mutations are used, at present, to define the high-risk PC population. Although there are some promising genomics markers to be used as early detection tests, none has been validated adequately to be integrated into the clinics routine. Conclusions: Despite of important efforts made in the recent time, little progress has been made to better characterise high-risk PC populations and to identify genomics-based markers for its early diagnosis. PC rates continue to rise, and this disease is becoming a real public health problem in the Westernised world. International and multidisciplinary strategies to identify new markers and properly validate the promising ones are urgently needed to implement cost-efficient primary and secondary prevention interventions in PC.

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RNA sequencing analyses reveal novel differentially expressed genes and pathways in pancreatic cancer

Cited by 51 publications

References 38 publications

Genetic polymorphisms associated with pancreatic cancer survival: a genome‐wide association study

Genetic polymorphisms associated with pancreatic cancer survival: a genome‐wide association study

Network‐based integration of mRNA and miRNA profiles reveals new target genes involved in pancreatic cancer

Genomics in Primary and Secondary Prevention of Pancreatic Cancer

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