High expression of ALDOA and DDX5 are associated with poor prognosis in human colorectal cancer

Abstract

PurposeThe identification of prognostic markers for colorectal cancer (CRC) is needed for clinical practice. Fructose-bisphosphate aldolase A (ALDOA) and DEAD box p68 RNA helicase (DDX5) are commonly overexpressed in cancer and correlate with tumorigenesis. However, association between expression of ALDOA and DDX5, and CRC outcome has not been reported.Patients and methodsWe used 141 formalin-fixed paraffin-embedded (FFPE) specimens collected from 105 patients with CRC treated at the Affiliated Hospital of Guilin Medical University and the People’s Hospital of Liuzhou. We performed tissue microarray based immunohistochemistry to explore expression features and prognostic value (overall survival, OS; disease-free survival, [DFS]) of ALDOA and DDX5 in CRC tissues. The prognostic values were evaluated using Kaplan–Meier analysis, and Cox regression analyses.ResultsALDOA and DDX5 were highly expressed in CRC tissues and liver metastatic CRC tissues compared with normal glandular epithelium tissues (all p<0.05). Interestingly, primary CRC tissues highly expressing ALDOA or DDX5 had poor outcome (p<0.0001 for both OS and DFS for ALDOA; p=0.001 for OS; and p=0.011 for DFS for DDX5) compared with patients who had low expression of those proteins. Furthermore, multivariate Cox analysis showed that ALDOA/DDX5 combination was an independent risk factor for OS and ALDOA was an independent risk factor for DFS.ConclusionHigh levels of ALDOA and DDX5 contribute to the aggressiveness and poor prognosis of CRC. ALDOA/DDX5 expression could be a biomarkers for the prognosis of CRC.

RETRACTED: DEAD-Box Helicase 5 Interacts With Transcription Factor 12 and Promotes the Progression of Osteosarcoma by Stimulating Cell Cycle Progression

“…This protein exerts multiple roles in RNA metabolism (Mazurek et al, 2012; Iyer et al, 2014; Samaan et al, 2014; Sarkar et al, 2015; Wang et al, 2015). In addition, the functions of DDX5 in tumorigenesis, apoptosis, and cancer development such as breast cancer (Guturi et al, 2014), prostate cancer (Clark et al, 2008), colorectal cancer (Dai et al, 2018), and esophageal cancer (Ma et al, 2017) have been established, but the role of DDX5 in OS remains unclear.…”

“…This result was in consistent with the findings of our previous studies (Liu et al, 2014; Wang et al, 2017). DDX5 was found to be related in carcinogenesis by accelerating cell proliferation and migration in colorectal cancer, breast cancer, and glioma, et al (Yang et al, 2006; Clark et al, 2008; Wagner et al, 2012; Wang D. et al, 2012; Wang R. et al, 2012; Wang et al, 2013; Lee et al, 2013; Dai et al, 2014; Mazurek et al, 2014; Dai et al, 2018).…”

“…DDX5 also plays an important role as a transcriptional co-activator with androgen receptor, vitamin D receptor, p53 and β-catenin (Clark et al, 2008; Wagner et al, 2012; Dai et al, 2014; Guturi et al, 2014). Recently, DDX5 was found to participate in tumorigenesis and development by promoting cell proliferation, metastasis (Wang et al, 2013), reorganization of cytoskeleton (Wang D. et al, 2012), and epithelial-mesenchymal transition (EMT) (Yang et al, 2006) of various cancers, such as breast cancer (Guturi et al, 2014), prostate cancer (Clark et al, 2008), colorectal cancer (Dai et al, 2018), glioma (Wang R. et al, 2012), and leukemia (Mazurek et al, 2014). DDX5 is associated with cellular transformation and EMT in colon cancer by activating β-catenin and upregulating the expression of Cyclin D1 gene (Yang et al, 2006, 2007).…”

Single-cell derived tumor organoids display diversity in HLA class I peptide presentation

“…6 ). ALDOA is a glycolytic enzyme observed to accumulate in CRC 38 , COPS6 is a subunit of the COP9 signalosome specifically required to drive CRC 39 – 41 , MCM2 functions as a DNA replication licensing factor needed to override once-per-cycle DNA replication in S-phase 42 , 43 and SMARCA4 (BRG1) is a SWI/SNF component activating WNT and VEGF signaling to drive CRC 31 , 44 , 45 . While HLA peptides from these four proteins were reliably detected on normal colon organoids, these were consistently absent from the ligandome of all four CRC organoid lines, suggesting that these proteins may be functionally important in CRC and therefore preserved from degradation (Supplementary Fig.…”

The effects and mechanisms of isoliquiritigenin loaded nanoliposomes regulated AMPK/mTOR mediated glycolysis in colorectal cancer

“…Noticeably, ALDOA and pyruvate kinase muscle isozyme M2 (PKM2), are also overexpressed in liver cirrhosis [14]. Other studies have shown an increased expression of the ALDOA, PKM2 and LDHA in the CRC, while the lactate dehydrogenase A (LDHA) expression could induce hypoxia-inducible factor 1-alpha (HIF-1a) [15,16]. The secretion of lactic acid from cells is catalysed by the reversible activity of the LDH and required monocarboxylic acid transporter (MCTs) to drive the reaction forward and prevent the high acidity of intracellular environment [17].…”