High Expression of ALDOA and DDX5 Are Associated with Poor Prognosis in Human Colorectal Cancer

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2018 Jul 11

PMID 29988738

Citations 28

Authors

Ling Dai

Guangdong Pan

Xiaojia Liu

Jiang Huang

Zhiqing Jiang

Xiaobao Zhu

Xinli Gan

Qing Xu

Ning Tan

Affiliations

Soon will be listed here.

Abstract

Purpose: The 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 Methods: We 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.

Results: ALDOA and DDX5 were highly expressed in CRC tissues and liver metastatic CRC tissues compared with normal glandular epithelium tissues (all <0.05). Interestingly, primary CRC tissues highly expressing ALDOA or DDX5 had poor outcome (<0.0001 for both OS and DFS for ALDOA; =0.001 for OS; and =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.

Conclusion: High 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.

Citing Articles

The multifaceted roles of aldolase A in cancer: glycolysis, cytoskeleton, translation and beyond.

Yu S, Xue Y, Chen Y, Cao Y, Yang Y, Ge X Hum Cell. 2025; 38(2):45.

PMID: 39808355 DOI: 10.1007/s13577-025-01172-4.

ALDOA contributes to colorectal tumorigenesis and metastasis by targeting YAP.

Sun L, Lu T, Jiang L, Yao H, Xu Q, Sun J Cell Death Discov. 2025; 10(1):489.

PMID: 39755705 PMC: 11700148. DOI: 10.1038/s41420-024-02249-z.

Diverse roles of aldolase enzymes in cancer development, drug resistance and therapeutic approaches as moonlighting enzymes.

Tang F, Cui Q Med Oncol. 2024; 41(9):224.

PMID: 39120781 DOI: 10.1007/s12032-024-02470-x.

FL118 Is a Potent Therapeutic Agent against Chronic Myeloid Leukemia Resistant to BCR-ABL Inhibitors through Targeting RNA Helicase DDX5.

Takeda K, Ohta S, Nagao M, Kobayashi E, Tago K, Funakoshi-Tago M Int J Mol Sci. 2024; 25(7).

PMID: 38612503 PMC: 11011477. DOI: 10.3390/ijms25073693.

Role and therapeutic potential of DEAD-box RNA helicase family in colorectal cancer.

Zheng B, Chen X, Ling Q, Cheng Q, Ye S Front Oncol. 2023; 13:1278282.

PMID: 38023215 PMC: 10654640. DOI: 10.3389/fonc.2023.1278282.

References

Peng Y, Li X, Wu M, Yang J, Liu M, Zhang W . New prognosis biomarkers identified by dynamic proteomic analysis of colorectal cancer. Mol Biosyst. 2012; 8(11):3077-88. DOI: 10.1039/c2mb25286d. View

Wang S, Zhang C, You Y, Shi C . Overexpression of RNA helicase p68 protein in cutaneous squamous cell carcinoma. Clin Exp Dermatol. 2012; 37(8):882-8. DOI: 10.1111/j.1365-2230.2012.04365.x. View

Sun H, Mi Y, Yu F, Han Y, Liu X, Lu S . SERPINA4 is a novel independent prognostic indicator and a potential therapeutic target for colorectal cancer. Am J Cancer Res. 2016; 6(8):1636-49. PMC: 5004069. View

Parkin D, Bray F, Ferlay J, Pisani P . Global cancer statistics, 2002. CA Cancer J Clin. 2005; 55(2):74-108. DOI: 10.3322/canjclin.55.2.74. View

Sambasivan R, Cheedipudi S, Pasupuleti N, Saleh A, Pavlath G, Dhawan J . The small chromatin-binding protein p8 coordinates the association of anti-proliferative and pro-myogenic proteins at the myogenin promoter. J Cell Sci. 2009; 122(Pt 19):3481-91. PMC: 2746131. DOI: 10.1242/jcs.048678. View

Camp R, Dolled-Filhart M, Rimm D . X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 2004; 10(21):7252-9. DOI: 10.1158/1078-0432.CCR-04-0713. View

Kim N, Lee M, Park J, Park D, Sohn C, Choi K . Serum CEA and CA 19-9 Levels are Associated with the Presence and Severity of Colorectal Neoplasia. Yonsei Med J. 2017; 58(5):918-924. PMC: 5552645. DOI: 10.3349/ymj.2017.58.5.918. View

Yu Z, Chen Z, Wu J, Li Z, Wu Y . Prognostic value of pretreatment serum carbohydrate antigen 19-9 level in patients with colorectal cancer: A meta-analysis. PLoS One. 2017; 12(11):e0188139. PMC: 5687748. DOI: 10.1371/journal.pone.0188139. View

Hurwitz H, Fehrenbacher L, Hainsworth J, Heim W, Berlin J, Holmgren E . Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer. J Clin Oncol. 2005; 23(15):3502-8. DOI: 10.1200/JCO.2005.10.017. View

10.

Puppa G, Sonzogni A, Colombari R, Pelosi G . TNM staging system of colorectal carcinoma: a critical appraisal of challenging issues. Arch Pathol Lab Med. 2010; 134(6):837-52. DOI: 10.5858/134.6.837. View

11.

Oparina N, Snezhkina A, Sadritdinova A, Veselovskii V, Dmitriev A, Senchenko V . [Differential expression of genes that encode glycolysis enzymes in kidney and lung cancer in humans]. Genetika. 2014; 49(7):814-23. DOI: 10.7868/s0016675813050111. View

12.

Singh C, Haines G, Talamonti M, Radosevich J . Expression of p68 in human colon cancer. Tumour Biol. 1995; 16(5):281-9. DOI: 10.1159/000217945. View

13.

Tokunaga R, Sakamoto Y, Nakagawa S, Miyamoto Y, Yoshida N, Oki E . Prognostic Nutritional Index Predicts Severe Complications, Recurrence, and Poor Prognosis in Patients With Colorectal Cancer Undergoing Primary Tumor Resection. Dis Colon Rectum. 2015; 58(11):1048-57. DOI: 10.1097/DCR.0000000000000458. View

14.

Fuller-Pace F, Moore H . RNA helicases p68 and p72: multifunctional proteins with important implications for cancer development. Future Oncol. 2011; 7(2):239-51. DOI: 10.2217/fon.11.1. View

15.

Chen W, Zheng R, Baade P, Zhang S, Zeng H, Bray F . Cancer statistics in China, 2015. CA Cancer J Clin. 2016; 66(2):115-32. DOI: 10.3322/caac.21338. View

16.

Tan N, Liu Q, Liu X, Gong Z, Zeng Y, Pan G . Low expression of B-cell-associated protein 31 in human primary hepatocellular carcinoma correlates with poor prognosis. Histopathology. 2015; 68(2):221-9. DOI: 10.1111/his.12738. View

17.

Wolpin B, Meyerhardt J, Mamon H, Mayer R . Adjuvant treatment of colorectal cancer. CA Cancer J Clin. 2007; 57(3):168-85. DOI: 10.3322/canjclin.57.3.168. View

18.

Lessa R, Campos A, Freitas C, Silva F, Kowalski L, Carvalho A . Identification of upregulated genes in oral squamous cell carcinomas. Head Neck. 2012; 35(10):1475-81. DOI: 10.1002/hed.23169. View

19.

Dai T, Cao L, Yang Z, Li Y, Tan L, Ran X . P68 RNA helicase as a molecular target for cancer therapy. J Exp Clin Cancer Res. 2014; 33:64. PMC: 4431487. DOI: 10.1186/s13046-014-0064-y. View

20.

Kukita A, Yoshida M, Fukushige S, Sakakibara M, Joh K, Mukai T . Molecular gene mapping of human aldolase A (ALDOA) gene to chromosome 16. Hum Genet. 1987; 76(1):20-6. DOI: 10.1007/BF00283044. View