Early dynamic transcriptomic changes during preoperative radiotherapy in patients with rectal cancer: A feasibility study

Supiot, S.; Gouraud, Wilfried; Campion, Loı̈c; Jézéquel, Pascal; Bruno, Benedetto; Charrier, J.; Heymann, Marie‐Françoise; Mahé, M.‐A.; Rio, E.; Chérel, Michel

doi:10.3748/wjg.v19.i21.3249

Cited by 33 publications

(36 citation statements)

References 42 publications

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“…[44][45][46] It is now well known that some CRC cases are linked to some factors, such as environment, 47 inflammation, 48,49 immunity, 50 and epigenetic alterations 51,52 rather than heritable genetic changes. An interesting thing is that these factors can influence each other, for instance, epigenetic aberrations induced by environmental factors contribute to cancer processes; 53 interaction of drug and molecular characteristics can influence lncRNAs and clinical outcome; 46,54,55 and epigenetic factors such as lncRNAs can also coordinate cellular responses to environment in turn. 56 The significance of lncRNAs in human CRC was realized in 2001 when Tanaka et al 57 determined that a loss of imprinting of long QT intronic transcript 1 (LIT1/KCNQ1OT1) was frequently observed in CRC patients, suggesting a link between lncRNAs and CRC.…”

Section: Lncrnas In Cancermentioning

confidence: 99%

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

Pan

2014

Modern Pathology

102

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Long non-coding RNAs (lncRNAs) are a class of newly identified non-coding RNA molecules that are emerging as key regulators of tumor initiation and development. Colorectal cancer (CRC) remains a major health problem worldwide, and there remains a need to further refine the current screening approaches as well as provide tailored diagnostic and therapeutic approaches. Multiple dysregulated lncRNAs participate in tumorigenesis through a variety of molecular mechanisms, and various regulatory factors frequently contribute to the aberrant expression of lncRNAs in CRC, thereby allowing malignant transformation. Additionally, the association of dysregulated lncRNAs with specific developmental stages and clinical outcomes indicates their potential as strong diagnostic and prognostic predictors as well as therapeutic targets. Here we provide a brief overview of the known functions of CRC-associated lncRNAs, describe some potential molecular mechanisms that underlie changes in lncRNA expression in CRC, and attempt to uncover their clinical and therapeutic potential. Keywords: colorectal cancer; diagnosis; dysregulation; long non-coding RNA; prognosis High-throughput genome-scale studies have demonstrated that more than 93% of the DNA sequences in the human genome are actively transcribed. 1 However, only approximately 5-10% of the sequences are stably transcribed into mRNA or non-coding RNA (ncRNA). Genome tiling arrays have revealed that the amount of non-coding sequence is at least four times larger than the amount of coding sequence, which indicates that only 1% of the human genome is composed of protein-coding genes and the remaining 4-9% is transcribed into ncRNAs. 2 Therefore, ncRNAs constitute a very large proportion of the total RNA molecules.The function and clinical significance of short regulatory ncRNAs, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), were elucidated first, 3 and the regulatory roles of miRNAs have been broadly recognized in almost all physiological and pathological processes in the body, including carcinogenesis. 4 For example, we previously reported that MIR95 promotes cell proliferation and targets sorting nexin 1 in human colorectal carcinoma; 5 moreover, in colorectal cancer (CRC) patients, the plasma levels of MIR29a and MIR92a are significantly upregulated and the plasma levels of MIR601 and MIR760 are significantly downregulated; thus the levels of these miRNAs have good diagnostic value for CRC screening. 6,7 According to their transcript size, ncRNAs are grouped into two major classes: (i) small ncRNAs with transcripts o200 nucleotides (nt; eg, aforementioned siRNAs and miRNAs, Piwi-interacting RNAs, and some retrotransposon-derived RNAs) and (ii) long non-coding RNAs (lncRNAs), this class includes five broad categories: sense, antisense, bidirectional, intronic, and intergenic, based on the proximity between neighboring transcripts. 8 For a time, lncRNAs was commonly defined as a proteincoding transcripts that is 4200 nt. 9 However, this definition is arbitrary and ...

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Section: Lncrnas In Cancermentioning

confidence: 99%

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

Pan

2014

Modern Pathology

102

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“…The gene expression profiles (ID, GSE26027) (12) were obtained from the Gene Expression Omnibus database (National Institutes of Health, Bethesda, MD, USA), which were previously produced based on the platform of Affymetrix Human Genome U133 Plus 2.0 Array (Affymetrix, Inc., Santa Clara, CA, USA). The biopsies for the microarray analysis were obtained from 6 patients with locally advanced rectal cancer prior to radiotherapy and 1 h subsequent to a dose of 7.2 Gy by the 4th fraction (1.8 Gy/fraction) during radiotherapy.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, a comprehensive evaluation of radiotherapy for the treatment of rectal cancer is required in order to develop effective therapeutic approaches for patients with rectal cancer. Previously, transcriptomic changes in response to radiotherapy in patients with rectal cancer using microarray data were revealed (12). However, only differential expression analysis and function analysis were performed in the aforementioned study, and the microarray data can be investigated reveal the molecular response to radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

“…However, only differential expression analysis and function analysis were performed in the aforementioned study, and the microarray data can be investigated reveal the molecular response to radiotherapy. The present study re-analyzed the gene expression profiles (12) of rectal cancer during and prior to radiotherapy to screen out differentially expressed genes (DEGs) with thresholds of the absolute value of log 2 fold change (FC) >1 and P<0.05 which were different compared with the criteria of FC (particularly the ratio 'gene expression during radiotherapy/gene expression prior to radiotherapy') >2.5 or <0.4 and false discovery rate <0.11. In addition, enrichment analyses and functional annotation were subsequently performed for DEGs to reveal their biological relevance.…”

Section: Introductionmentioning

confidence: 99%

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Identification of molecular characteristics induced by radiotherapy in rectal cancer based on microarray data

Chen

et al. 2017

Oncology Letters

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Abstract. The present study aimed to reveal the molecular characteristics induced by radiotherapy in rectal cancer at the transcriptome level. Microarray data (ID, GSE26027) downloaded from the Gene Expression Omnibus database were re-analyzed to identify differentially expressed genes (DEGs) between rectal cancer tissues during and prior to radiotherapy. The DEGs were then inputted into the database for annotation, visualization and integrated discovery, an online tool to perform enrichment analyses, and into the search tool for the retrieval of interacting genes/proteins database to identify protein-protein interactions (PPIs). Subsequently, a PPI network was constructed, which was screened for densely connected modules. Furthermore, protein domain enrichment analysis was performed. In total, 690 DEGs, including 179 upregulated and 511 downregulated DEGs, were found in rectal cancer tissues during and prior to radiotherapy. The upregulated DEGs were significantly enriched in 'positive regulation of transport' and 'regulation of cardiac muscle contraction', while the downregulated DEGs were most markedly enriched in 'cell migration', 'cell-cell signaling', 'extracellular matrix organization' and 'blood vessel development', including prostaglandin-endoperoxide synthase 2, transforming growth factor β-induced, 68 kDa endothelin receptor type A, brain-derived neurotrophic factor, TIMP metallopeptidase inhibitor 1, and serpin family E member 1, which were the top 6 hub nodes in the PPI network. Furthermore, 2 protein domains were significantly enriched by PPI modules, including: The collagen triple helix repeat (CTHR) family members collagen type (COL) 5A2, COL9A3, COL6A3, COL21A1, COL5A3, COL11A1, COL7A1 and CTHR-containing-1; and the olfactory receptor family (OR) members OR7E24, OR7A17, OR6A2, OR1F1, OR10H3 and OR7A10. A total of 7 upregulated DEGs were characterized as tumor suppressor genes, and 8 downregulated DEGs were characterized as oncogenes. The biological processes or protein domains enriched by upregulated or downregulated DEGs may improve the understanding of molecular characteristics in response to radiotherapy.

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“…In another study, based on biopsy specimens obtained 7 days after starting CRT, the expressions of p21 and apoptosis have been proven to be strong predictors of the response to CRT in rectal cancer (48). Gene expression changes detected on biopsies after a dose of 7.2 Gy at a median time of 1 hour following irradiation found 31 genes significantly up-regulated and 6 genes down-regulated (81). This potentially means that the response may be more accurately predicted after initial treatment cycles rather than only before or after treatment of tissues, but performing serial biopsies is an invasive and unpleasant procedure and has the risk of increasing toxicity from repeated biopsies.…”

Section: Dynamic Analyzingmentioning

confidence: 99%

Prediction of response to preoperative chemoradiotherapy in patients with locally advanced rectal cancer

Meng

Huang

Wang

et al. 2014

BST

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Early dynamic transcriptomic changes during preoperative radiotherapy in patients with rectal cancer: A feasibility study

Abstract: Micro-arrays can efficiently assess early transcriptomic changes during preoperative radiotherapy for rectal cancer, and may help better understand tumor radioresistance.

Cited by 33 publications

References 42 publications

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

Identification of molecular characteristics induced by radiotherapy in rectal cancer based on microarray data

Prediction of response to preoperative chemoradiotherapy in patients with locally advanced rectal cancer

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