Novel reference genes in colorectal cancer identify a distinct subset of high stage tumors and their associated histologically normal colonic tissues

Xu, Lai; Luo, Helen; Wang, Rong; Wu, Wells W.; Phue, Je-Nie; Shen, Rong; Juhl, Hartmut; Wu, Leihong; Alterovitz, Wei Lun; Simonyan, Vahan; Pelosof, Lorraine; Rosenberg, Amy S.

doi:10.1186/s12881-019-0867-y

Cited by 15 publications

(19 citation statements)

References 46 publications

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“…NGS is a technology that accurately quantifies gene expression and does not necessarily require further validation, as supported by the literature (25). To more fully establish NGS as a "stand alone" technology for gene quantification, we reasoned that NGS quantification of a critical hub gene should be reflected in the consequent up/downregulation of highly interconnected genes and thus examined the co-expression of IFNγ genes with T and NK cell specific genes based on the fact that IFNγ and granzymes are produced by T cells and NK cells (30)…”

Section: Ngs Evaluation Of Immune Gene Expressionmentioning

confidence: 92%

“…Ten thousand two hundred fifty-five genes (40% of total genes) had an average FPKM > 1 and differential expression between tumors and normal controls (False Discovery Rate (FDR) < 0.05 in ANOVA). A total of 3,893 genes (15% of total genes) with average FPKM > 1 showed no differential expression between tumor and normal controls with FDR (ANOVA) > 0.05 (25,29).…”

Section: Initial Expression Landscape Of Crcmentioning

confidence: 99%

“…According to the medical pathology reports, tumors were classified as well, moderately, and poorly differentiated tumors following international guideline UICC TNM-classification (24). For the convenience of analysis, 26 stage I and II tumors were considered as low stage tumors (LSTs), while 53 stage III and IV tumors were considered as HSTs (25). In this study, a normal control adjacent to a low stage tumor is referred to as LSN.…”

Section: Cohortmentioning

confidence: 99%

“…Cufflinks V.2.2.1 was used to assemble the transcriptome based on the hg19 reference annotation, and Cuffquan/Cuffnorm (part of Cufflinks) were used in calculating relative abundance of each transcript reported as FPKM. Gene co-expression analyses were carried by Partek NGS & microarray data analysis software (25,28,29). Integrated Discovery (DAVID) v6.7 (https://david.ncifcrf.gov/) was used for biological pathway determination and Cytoscape (2.8.2) was used for gene coexpression networks construction.…”

Section: Sequencing Data Analysismentioning

confidence: 99%

“…A total of 25,761 genes were detected. Because genes with higher FPKM values may have greater biological impact, we focused on genes with FPKM > 1 (25,28). Ten thousand two hundred fifty-five genes (40% of total genes) had an average FPKM > 1 and differential expression between tumors and normal controls (False Discovery Rate (FDR) < 0.05 in ANOVA).…”

Section: Initial Expression Landscape Of Crcmentioning

confidence: 99%

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NGS Evaluation of Colorectal Cancer Reveals Interferon Gamma Dependent Expression of Immune Checkpoint Genes and Identification of Novel IFNγ Induced Genes

Pelosof

Wang

et al. 2020

Front. Immunol.

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To evaluate the expression of immune checkpoint genes, their concordance with expression of IFNγ, and to identify potential novel ICP related genes (ICPRG) in colorectal cancer (CRC), the biological connectivity of six well documented ("classical") ICPs (CTLA4, PD1, PDL1, Tim3, IDO1, and LAG3) with IFNγ and its co-expressed genes was examined by NGS in 79 CRC/healthy colon tissue pairs. Identification of novel IFNγ-induced molecules with potential ICP activity was also sought. In our study, the six classical ICPs were statistically upregulated and correlated with IFNγ, CD8A, CD8B, CD4, and 180 additional immunologically related genes in IFNγ positive (FPKM > 1) tumors. By ICP co-expression analysis, we also identified three IFNγ-induced genes [(IFNγ-inducible lysosomal thiol reductase (IFI30), guanylate binding protein1 (GBP1), and guanylate binding protein 4 (GBP4)] as potential novel ICPRGs. These three genes were upregulated in tumor compared to normal tissues in IFNγ positive tumors, co-expressed with CD8A and had relatively high abundance (average FPKM = 362, 51, and 25, respectively), compared to the abundance of the 5 well-defined ICPs (Tim3, LAG3, PDL1, CTLA4, PD1; average FPKM = 10, 9, 6, 6, and 2, respectively), although IDO1 is expressed at comparably high levels (FPKM = 39). We extended our evaluation by querying the TCGA database which revealed the commonality of IFNγ dependent expression of the three potential ICPRGs in 638 CRCs, 103 skin cutaneous melanomas (SKCM), 1105 breast cancers (BC), 184 esophageal cancers (ESC), 416 stomach cancers (STC), and 501 lung squamous carcinomas (LUSC). In terms of prognosis, based on Pathology Atlas data, correlation of GBP1 and GBP4, but not IFI30, with 5-year survival rate was favorable in CRC, BC, SKCM, and STC. Thus, further studies defining the role of IFI30, GBP1, and GBP4 in CRC are warranted.

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Section: Ngs Evaluation Of Immune Gene Expressionmentioning

confidence: 92%

Section: Initial Expression Landscape Of Crcmentioning

confidence: 99%

Section: Cohortmentioning

confidence: 99%

Section: Sequencing Data Analysismentioning

confidence: 99%

Section: Initial Expression Landscape Of Crcmentioning

confidence: 99%

See 3 more Smart Citations

NGS Evaluation of Colorectal Cancer Reveals Interferon Gamma Dependent Expression of Immune Checkpoint Genes and Identification of Novel IFNγ Induced Genes

Pelosof

Wang

et al. 2020

Front. Immunol.

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An investigation on the c‐MYC, AXIN1, and COL11A1 gene expression in colorectal cancer

Moradifard

Minuchehr

Ganji

2021

Biotech and App Biochem

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The high incidence rate of CRC demands early diagnosis of the disease and readiness of diagnostic biomarker. In present study, we have investigated c‐MYC, AXIN1, and COL11A1 expression levels in course of CRC progression and their correlation with demographics and clinical risk factors. Fifty‐five tumors and 41 normal tissues were obtained from Tumor Bank of Iran, total RNA was extracted, cDNA was synthesized, and RT‐qPCR was performed. Results were analyzed using Rest 2009 and SPSS software. Analysis at mRNA level showed upregulation of the two genes; c‐MYC with a p‐value of 0.001 and COL11A1 with an observed p‐value of 0.02, while a p‐value of 0.04 indicated AXIN1 downregulation. The observed overexpression of COL11A1 in stage 0 compared to other stages of CRC asserts importance of this gene in CRC prognosis. Moreover, statistical analysis confirms a significant correlation between expression of these genes and several clinical risk factors of CRC. Our study supports the importance of the studied genes and provides further information regarding the molecular mechanism of CRC. Further studies on these genes could elucidate their pivotal role for both early detection and/or diagnosis of CRC in addition to have important biomarkers for CRC management available.

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Extracellular vesicles from colorectal cancer cells promote metastasis via the NOD1 signalling pathway

Wei

Pei

et al. 2022

J of Extracellular Vesicle

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Pattern-recognition receptors (PRRs) have been shown to promote tumour metastasis via sensing tumour cell-derived small extracellular vesicles (EVs). Nucleotidebinding oligomerisation domain 1 (NOD1), a cytoplasmic PRR, plays a role in colorectal cancer (CRC) by detecting bacterial products. However, the precise mechanisms underlying the effects of NOD1, following identification of CRC cell-derived EVs (CRC-EVs), to potentiate CRC liver metastasis (CRC-LM), remain poorly understood. Here, we demonstrate that CRC-EVs activate NOD1 in macrophages to initiate secretion of inflammatory cytokines and chemokines. NOD1-activated macrophages also promote CRC cell migration, while in a murine model of liver metastasis (LM), NOD1-deficient mice exhibit reduced metastasis following CRC-EV treatment. Furthermore, cell division cycle 42 (CDC42), a small Rho guanosine-5′-triphosphate (GTP)ase, is delivered by CRC-EVs into macrophages where it activates NOD1. In addition, EVs from the plasma of patients with CRC-LM mediate NOD1 activation in human peripheral blood mononuclear cells. Moreover, high NOD1 expression in tumour tissues is associated with poor prognosis of CRC-LM. Our findings suggest that CRC-EVs activate NOD1 to promote tumour metastasis, thus, NOD1 may serve as a potential target in the diagnosis and treatment of CRC-LM.

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Novel reference genes in colorectal cancer identify a distinct subset of high stage tumors and their associated histologically normal colonic tissues

Cited by 15 publications

References 46 publications

NGS Evaluation of Colorectal Cancer Reveals Interferon Gamma Dependent Expression of Immune Checkpoint Genes and Identification of Novel IFNγ Induced Genes

NGS Evaluation of Colorectal Cancer Reveals Interferon Gamma Dependent Expression of Immune Checkpoint Genes and Identification of Novel IFNγ Induced Genes

An investigation on the c‐MYC, AXIN1, and COL11A1 gene expression in colorectal cancer

Extracellular vesicles from colorectal cancer cells promote metastasis via the NOD1 signalling pathway

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