Visualization of epithelial-mesenchymal transition in an inflammatory microenvironment–colorectal cancer network

Ieda, Takeshi; Tazawa, Hiroshi; Okabayashi, Hiroshi; Yano, Shuya; Shigeyasu, Kunitoshi; Kuroda, Shigetoshi; Ohara, Toshiaki; Noma, Kazuhiro; Kishimoto, Hiroyuki; Nishizaki, Masahiko; Kagawa, Shunsuke; Shirakawa, Yasuhiro; Saitou, Takashi; Imamura, Takeshi; Fujiwara, Toshiyoshi

doi:10.1038/s41598-019-52816-z

Cited by 40 publications

(36 citation statements)

References 57 publications

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“…An important implication in EMT was also revealed by IL-22 in relation with IL-1β 29 , which was shown to be critically involved in CRC cell metastasis 30 We showed an important correlation between IL-8, IL-1β, MMP-2 and IL-22 ( Fig. 3 and Fig.…”

Section: Il-8 An Important Cross-link Point In Cytokines Constellationmentioning

confidence: 58%

Key Biomarkers Within the Colorectal Cancer Related Inflammatory Microenvironment

Calu

Ionescu

Stanca

et al. 2020

Preprint

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The necessity of therapeutic approaches focused on the inflammatory microenvironment of colorectal cancer (CRC) is becoming more and more apparent, both in order to improve post-surgical care and subsequent therapeutic strategies, and also for better quality of life for the patients. We have investigated a panel of 39 inflammatory factors using a multiplex magnetic bead-based immunoassay, in relation with CEA and CA19-9, classical tumor markers and the expression levels of pErk, occludin, and STAT1 and STAT3 transcriptional factors. Within the tumor and paired normal tissue samples collected during tumor resection surgery, we have identified 32 biomarkers displaying statistically significant differences. Several relevant correlations have been observed in a combined multi-type correlation matrix. Chitinase 3-like 1 seems to be a trigger for activation pathways for tumor growth and metastasis. Through IL-22 and IL1β, IL-8 correlates indirectly with CA19-9 and CEA, respectively. We also emphasize the diminished APRIL and high BAFF levels in colon cancer tumor tissue, which is quite unique. The strong correlation between APRIL, BAFF, IL-8 and MMP2 recommends these as combined targets in immunotherapies for colon cancer treatment, and indicates the marker quartet may serve as a starting point in colon cancer screening.

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Section: Il-8 An Important Cross-link Point In Cytokines Constellationmentioning

confidence: 58%

Key Biomarkers Within the Colorectal Cancer Related Inflammatory Microenvironment

Calu

Ionescu

Stanca

et al. 2020

Preprint

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“…An important implication in EMT was also revealed by IL-22 in relation with IL-1β 28 , which was shown to be critically involved in CRC cell metastasis 29 . We showed an important correlation between IL-8, IL-1β, MMP-2 and IL-22 (Figs.…”

Section: Discussionmentioning

confidence: 97%

Key biomarkers within the colorectal cancer related inflammatory microenvironment

Calu

Ionescu

Stanca

et al. 2021

Sci Rep

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Therapeutic approaches focused on the inflammatory microenvironment are currently gaining more support, as biomolecules involved in the inflammatory colorectal cancer (CRC) tumor microenvironment are being explored. We analyzed tumor and paired normal tissue samples from CRC patients (n = 22) whom underwent tumor resection surgery. We assessed 39 inflammation-involved biomolecules (multiplex magnetic bead-based immunoassay), CEA and CA19-9 (ELISA assay) and the tissue expression levels of occludin and also pErk, STAT1 and STAT3 transcriptional factors (western blot). Tumor staging has been established by histopathological evaluation of HE stained tumor tissue sections. We report 32 biomarkers displaying statistically significant differences in tumor vs. control. Additionally, positive statistical biomarker correlations were found between MMP2–IL8 and BAFF–IL8 (Pearson correlation coefficients > 0.751), while APRIL–MMP2, APRIL–BAFF and APRIL–IL8 were negatively correlated (correlation coefficients < − 0.650). While APRIL, BAFF, IL8 and MMP2 did not modulate with tumor stage, they were inversely related to the immune infiltrate level and CD163 tissue expression. We conclude that the significantly decreased APRIL and increased BAFF, IL8 and MMP2 expression were tumor-specific and deserve consideration in the development of new treatments. Also, the positive correlation between Chitinase 3-like 1 and IL8 (0.57) or MMP2 (0.50) suggest a role in tumor growth and metastasis pathways.

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“…TGFbeta signaling is associated with EMT and therefore could present a potential link between miR-487a-3p and EMT. The process of EMT is closely associated with therapy resistance in various cancers, including CRC (29,30).…”

Section: Discussionmentioning

confidence: 99%

Tumor microRNAs Identified by Small RNA Sequencing as Potential Response Predictors in Locally Advanced Rectal Cancer Patients Treated With Neoadjuvant Chemoradiotherapy

Macháčková

Trachtová

Procházka

et al. 2020

Cancer Genomics Proteomics

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Background/Aim: Rectal cancer accounts for approximately one-third of all colorectal cancers. Currently, the standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (CRT) with capecitabine or 5-fluorouracil followed by curative surgery. Unfortunately, only 20% of patients with LARC present complete pathological response after CRT, whereas in 20-40% cases the response is poor or absent. The aim of our study was to evaluate whether microRNAs (miRNAs) in tumor biopsy specimen have the potential to predict therapeutic response in LARC patients. Patients and Methods: In total 87 LARC patients treated by CRT were enrolled in our prospective study. To identify predictive miRNAs, we used small RNA sequencing in 40 tumor biopsy samples of LARC patients (20 responders, 20 non-responders) and qPCR validation of selected miRNA candidates. Results: In the discovery phase of the study, we identified 69 miRNAs to have significantly different expression between the group of responders (TRG 1,2) and a group of non-responders (TRG 4,5) to neoadjuvant CRT. Among these miRNAs, 48 showed a lower expression and 21 showed higher expression in tumor tissues from poorly responding LARC patients. Five miRNAs were selected for validation, but only miR-487a-3p was confirmed to have a significantly higher expression in the tumor biopsy specimens of non-responders to neoadjuvant CRT (p<0.0006, AUC=0.766). Gene Ontology (GO) clustering and pathway enrichment analysis of the miR-487a-3p mRNA targets, revealed potential mechanisms behind miR-487a-3p roles in chemoradioresistance (e.g. TGF-beta signaling pathway, protein kinase activity, double-stranded DNA binding, or microRNAs in cancer). Conclusion: By combination of miRNA expression profiling and integrative computational biology we identified miR-487a-3p as a potential predictive biomarker of CRT response in LARC patients. Colorectal cancer (CRC) is the third most common cancer worldwide and accounts for approximately 10% of all solid tumors. CRC is the second leading cause of cancer-related deaths, and its incidence is on the rise. Tumors of the rectum 249 This article is freely accessible online.

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Visualization of epithelial-mesenchymal transition in an inflammatory microenvironment–colorectal cancer network

Cited by 40 publications

References 57 publications

Key Biomarkers Within the Colorectal Cancer Related Inflammatory Microenvironment

Key Biomarkers Within the Colorectal Cancer Related Inflammatory Microenvironment

Key biomarkers within the colorectal cancer related inflammatory microenvironment

Tumor microRNAs Identified by Small RNA Sequencing as Potential Response Predictors in Locally Advanced Rectal Cancer Patients Treated With Neoadjuvant Chemoradiotherapy

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