Altered RECQ Helicase Expression in Sporadic Primary Colorectal Cancers

Abstract

Deregulation of DNA repair enzymes occurs in cancers and may create a susceptibility to chemotherapy. Expression levels of DNA repair enzymes have been shown to predict the responsiveness of cancers to certain chemotherapeutic agents. The RECQ helicases repair damaged DNA including damage caused by topoisomerase I inhibitors, such as irinotecan. Altered expression levels of these enzymes in colorectal cancer (CRC) may influence the response of the cancers to irinotecan. Thus, we assessed RECQ helicase (WRN, BLM, RECQL, RECQL4, and RECQL5) expression in primary CRCs, matched normal colon, and CRC cell lines. We found that BLM and RECQL4 mRNA levels are significantly increased in CRC (P = .0011 and P < .0001, respectively), whereas RECQL and RECQL5 are significantly decreased (P = .0103 and P = .0029, respectively). RECQ helicase expression patterns varied between specific molecular subtypes of CRCs. The mRNA and protein expression of the majority of the RECQ helicases was closely correlated, suggesting that altered mRNA expression is the predominant mechanism for deregulated RECQ helicase expression. Immunohistochemistry localized the RECQ helicases to the nucleus. RECQ helicase expression is altered in CRC, suggesting that RECQ helicase expression has potential to identify CRCs that are susceptible to specific chemotherapeutic agents.

The ColoCare Study: A Paradigm of Transdisciplinary Science in Colorectal Cancer Outcomes

“…Components of the ColoCare Cohort have been leveraged to support initial research; including on biologic determinants of colorectal cancer (e.g., tumor immunity, gut microbiome, epigenome), health behaviors (e.g., physical activity or dietary patterns), components of energy balance (e.g., adipose tissue distribution, accelerometry), clinical endpoints (e.g., surgical complications, quality of life), and novel biomarkers (proteomics, metabolomics, metagenomics). Furthermore, we have published on the interrelations between these factors, specifically in the context of colorectal cancer prognosis (18,(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48). Table 3 highlights research contributions using the growing ColoCare Study cohort.…”

Association of Beclin-1 and microRNA-30a expression with the severity and treatment response of colorectal cancer

“…Molecular alteration would affect the biological processes mediating how tumor genesis cells respond to the environment (Lao et al, 2013). CRC patients in TNM II stage and III stage need surgical resection combined with post-operative adjuvant chemotherapy.…”

“…CRC patients in TNM II stage and III stage need surgical resection combined with post-operative adjuvant chemotherapy. However, 30-40% of those patients lose their battle against CRC after therapies (Lao et al, 2013). CRC recurrences usually happen in 5 years and patients with recurrences have poor responses towards proposed post-operative adjuvant chemotherapy.…”

Human RECQ helicases: roles in cancer, aging, and inherited disease

“…Loss, silencing, or altered expression of RECQ genes, in contrast, may be frequent in many tumor types including common adult epithelial cancers such as breast and colorectal cancer. 173 Promoter region and gene body methylation have been suggested as one cause for loss of WRN expression in human tumors. [174][175][176] However, the relationship between methylation and loss of expression does not appear to be consistent enough in our and in others' hands to be useful alone as a surrogate expression marker (Bosch et al, unpublished results).…”