J Cancer 2017; 8(7):1197-1204. doi:10.7150/jca.18197
High Expression of Aldolase B Confers a Poor Prognosis for Rectal Cancer Patients Receiving Neoadjuvant Chemoradiotherapy
1. Division of General Surgery, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan;
2. Department of Health & Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan;
3. Department of Medical Image, Chi Mei Medical Center, Tainan, Taiwan;
4. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan;
5. Department of Leisure, Recreation, and Tourism Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan;
6. Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, Taiwan;
7. Department of Radiation Oncology, Chi-Mei Medical Center, Tainan, Taiwan;
8. Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan;
9. School of Medicine, I-Shou University, Kaohsiung, Taiwan;
10. Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan;
11. National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan;
12. Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan;
13. Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Tian YF, Hsieh PL, Lin CY, Sun DP, Sheu MJ, Yang CC, Lin LC, He HL, Solórzano J, Li CF, Chang IW. High Expression of Aldolase B Confers a Poor Prognosis for Rectal Cancer Patients Receiving Neoadjuvant Chemoradiotherapy. J Cancer 2017; 8(7):1197-1204. doi:10.7150/jca.18197. Available from http://www.jcancer.org/v08p1197.htm
Background: Colorectal cancer is the third most common cancer in both sex worldwide and it is also the fourth most common cause of cancer mortality. For rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) followed by radical proctectomy is gold standard treatment for patients with stage II/III rectal cancer. By data mining a documented database of rectal cancer transcriptome (GSE35452) from Gene Expression Omnibus, National Center of Biotechnology Information, we recognized that ALDOB was the most significantly up-regulated transcript among those related to glycolysis (GO: 0006096). Hence, we analyzed the clinicopathological correlation and prognostic effect of ALDOB protein (Aldolase B), which encoded by ALDOB gene.
Methods: ALDOB immunostain was performed in 172 rectal adenocarcinomas treated with preoperative chemoradiotherapy followed by radical surgery, which were divided into high- and low-expression groups. Furthermore, statistical analyses were examined to correlate the relationship between ALDOB immunoreactivity and important clinical and pathological characteristics, as well as three survival indices: disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS).
Results: ALDOB (Aldolase B) over-expression was significantly associated with pre-CCRT and post-CCRT tumor advancement, lymphovascular invasion, perineural invasion and poor response to CCRT (all P ≤ .023). In addition, ALDOB high expression was linked to adverse DSS, LRFS and MeFS in univariate analysis (P ≤ .0075) and also served as an independent prognosticator indicating dismal DSS and MeFS in multivariate analysis (hazard ratio (HR) = 3.462, 95% confidence interval (CI): 1.263-9.495; HR = 2.846, 95% CI: 1.190-6.808, respectively).
Conclusion: ALDOB (Aldolase B) may play an imperative role in rectal cancer progression and responsiveness to neoadjuvant CCRT, and serve as a novel prognostic biomarker. Additional researches to clarify the molecular and biochemical pathways are essential for developing promising ALDOB-targeted therapies for patients with rectal cancers.
Keywords: ALDOB, Aldolase B, CCRT, chemoradiotherapy, rectal cancer.