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Erschienen in: Journal of Cancer Research and Clinical Oncology 3/2012

01.03.2012 | Original Paper

ARNTL2 and SERPINE1: potential biomarkers for tumor aggressiveness in colorectal cancer

verfasst von: Gianluigi Mazzoccoli, Valerio Pazienza, Anna Panza, Maria Rosa Valvano, Giorgia Benegiamo, Manlio Vinciguerra, Angelo Andriulli, Ada Piepoli

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 3/2012

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Abstract

Purpose

Cathepsin and plasmin may favor cancer cell invasion degrading extracellular matrix. Plasmin formation from plasminogen is regulated by plasminogen activator inhibitor type-1 (PAI-1). ARNTL2 activates the promoters of the PAI-1 gene, officially called SERPINE1, driving the circadian variation in circulating PAI-1 levels.

Methods

We evaluated ARNTL2 and SERPINE1 expression in 50 colorectal cancer specimens and adjacent normal tissue and in colon cancer cell lines.

Results

We found up-regulation of ARNTL2 (P = 0.004) and SERPINE1 (P = 0.002) in tumor tissue. A statistically significant association was found between high ARNTL2 mRNA levels and vascular invasion (P < 0.0001), and between high SERPINE1 mRNA levels and microsatellite instability (MSI-H and MSI-L, P = 0.025). Sorting the subjects into quartile groups, a statistically significant association was found between high ARNTL2 expression and lymph node involvement (P < 0.001), between high SERPINE1 expression and grading (P < 0.001) and between high SERPINE1 expression and MSI H–L (P < 0.0001). In SW480 cells, a more proliferative model compared to CaCo2 cells, there were higher mRNA levels of ARNTL2 (P < 0.001) and SERPINE1 (P = 0.001).

Conclusion

ARNTL2 and SERPINE1 expression is increased in colorectal cancer and in a highly proliferative colon cancer cell line and is related to tumor invasiveness and aggressiveness.
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Metadaten
Titel
ARNTL2 and SERPINE1: potential biomarkers for tumor aggressiveness in colorectal cancer
verfasst von
Gianluigi Mazzoccoli
Valerio Pazienza
Anna Panza
Maria Rosa Valvano
Giorgia Benegiamo
Manlio Vinciguerra
Angelo Andriulli
Ada Piepoli
Publikationsdatum
01.03.2012
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 3/2012
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-011-1126-6

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