High expression of AMPD2 and obesity are associated with poor prognosis in colorectal cancer

Fang Wang; Yankui Liu; Jifeng Jiang; Yan Qin; Xiaosong Ge; Jinping Li; Xiaowei Qi; Yong Mao

High expression of AMPD2 and obesity are associated with poor prognosis in colorectal cancer

Int J Clin Exp Pathol. 2018 Jan 1;11(1):216-223. eCollection 2018.

Authors

Fang Wang^{1

2

3}, Yankui Liu¹, Jifeng Jiang⁴, Yan Qin¹, Xiaosong Ge², Jinping Li³, Xiaowei Qi¹, Yong Mao²

Affiliations

¹ Department of Pathology, Affiliated Hospital of Jiangnan University Wuxi, China.
² Department of Oncology, Affiliated Hospital of Jiangnan University Wuxi, China.
³ Department of Epidemiology and Biostatistics, School of Medicine, Jiangnan University Wuxi, China.
⁴ Department of Hematology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai, China.

PMID: 31938103
PMCID: PMC6957932

Abstract

The protein-coding gene adenosine monophosphate deaminase (AMPD) 2 plays a critical role in energy metabolism by converting adenosine-5-monophosphate (AMP) to iosine inosine-5-monophosphate (IMP). Obesity affects metabolic abnormalities in tumor cells and has been associated with high expression levels of AMPD2 and colorectal cancer (CRC). In this study, we performed immunohistochemical analysis of AMPD2 expression in 158 patients with CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine AMPD2 mRNA expression levels, which were validated by The Cancer Genome Atlas (TCGA) datasets. Chi-square test and Fisher's exact test were used to evaluate the correlation between the expression of AMPD2 and clinicopathological parameters of CRC. Overall survival (OS) rates of the CRC patients were calculated using Kaplan-Meier survival analysis and a Cox proportional regression model was performed for univariate and multivariate analysis. A logistic regression model was used to plot the receiver operating characteristic (ROC) curve and to evaluate the predictive effect of multivariate studies on prognosis outcomes of CRC. We found a significant increase in AMPD2 expression in tumor tissue (91.8%, 146/158) compared to adjacent normal tissue (52.5%, 83/158, P < 0.01). The positive rate of AMPD2 expression was 72.7% (39/54) in overweight individuals versus 51.9% (54/104) in individuals with a normal weight (P = 0.014). AMPD2 mRNA levels as determined by qRT-PCR elevated levels of AMPD2 transcripts were higher in CRC samples compared to adjacent normal tissues (P < 0.05). In both the TCGA colon adenocarcinoma and rectal adenocarcinoma dataset, the number of CRC patients with increased levels of AMPD2 in tumor tissues was significantly higher compared to patients with adjacent normal tissue (P < 0.001). High expression of AMPD2 was associated with TNM stage, higher histological grade, obesity, and lower OS rates in patients with CRC. Obesity and high expression of AMPD2 in patients are with poor prognosis. Moreover, multivariate analysis indicated that AMPD2 levels and TNM stage were significant independent prognostic factors in CRC patients. The logistic regression predictive effect of the area under the curve (AUC) was 0.821 (P < 0.001). In conclusion, high levels of AMPD2 and obesity are associated with poor prognosis in patients with CRC.

Keywords: AMPD2; Colorectal cancer; immunohistochemistry; obesity; survival analysis.