High Expression of Aldolase B Confers a Poor Prognosis for Rectal Cancer Patients Receiving Neoadjuvant Chemoradiotherapy

Abstract

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.

Papillary renal cell carcinomas rewire glutathione metabolism and are deficient in anabolic glucose synthesis

“…This again indicates a critical metabolic change, as previously observed in chRCC (27) and in gastric cancer (35). Conversely, an over-expression of gluconeogenic genes and proteins is frequently found in other tumor species, such as the over-expression of ALDOB in ccRCC (36) and colon cancer (37)(38)(39), which was also associated with tumor progression and poor prognosis.…”

Metabolic reprogramming and elevation of glutathione in chromophobe renal cell carcinomas

“…Specifically, increased ALDOB expression was found to favor cancer cell proliferation and metastasis in multiple cancers, such as colon cancer (Bu et al, 2018), rectal cancer (Tian et al, 2017), and colorectal adenocarcinoma . This might also be one reason for the low metastatic potential (Volpe et al, 2012) and the high survival rate of chRCC patients (Amin et al, 2002;Przybycin et al, 2011).…”

Identification of ceRNA network based on a RNA‑seq shows prognostic lncRNA biomarkers in human lung adenocarcinoma

“…Abnormal changes in ALDOB are associated with a number of diseases, including hereditary fructose intolerance, hepatitis, cirrhosis and cancer ( 64 ). Using data mined from the Gene Expression Omnibus for the colorectal cancer transcriptome (GSE35452) database, Tian et al ( 65 ) reported that ALDOB is associated with glycolysis and is the most significantly increased transcript (GO: 0006096). It may serve a significant role in colorectal cancer progression and the response to neoadjuvant concurrent chemoradiotherapy, and as a novel prognostic biomarker.…”