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, 11 (1), 216-223
eCollection

High Expression of AMPD2 and Obesity Are Associated With Poor Prognosis in Colorectal Cancer

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High Expression of AMPD2 and Obesity Are Associated With Poor Prognosis in Colorectal Cancer

Fang Wang et al. Int J Clin Exp Pathol.

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.

Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Representative Immunohistochemical results of AMPD2 levels in colorectal cancer patients. Tissue of tumor specimens (Aa, Ab) from the same patient as adjacent normal tissue (Ba, Bb). (A, Ba) Are typical representative images, which showed that AMPD2 expression is elevated in the tumor tissue (T) compared to adjacent normal mucosa (N). (Ca, Cb) In 12 patients, AMPD2 expression could not be observed. The photomicrographs were at 100× and 400× magnification.
Figure 2
Figure 2
Expression levels of AMPD2 using immunohistochemistry scores may serve as significant prognostic markers in classification of colorectal cancer. A receiver operating characteristic (ROC) curve built on the univariate classification model based on the immunohistochemical scores of AMPD2 expression of 158 patients for predicting the outcome of overall survival (A). The immunohistochemical scores were determined by fractional t-test of obese and non-obese patients (B).
Figure 3
Figure 3
Survival cumulative probabilities classified by AMPD2 score. Kaplan-Meier overall survival curves for patients with a positive versus a negative AMPD2 score. P values were calculated using the log-rank test (A). Kaplan-Meier plots for overall survival of discriminatory Chinese Nutrition Society criteria to determine obesity (overweight, BMI ≥ 28 kg/m2; normal weight, 18.5 kg/m2-28 kg/m2; undernourished, BMI < 18.5). P values were calculated using the log-rank test (B). A ROC curve built to performance of the multivariate regression prediction model on the prognosis with 158 patients with CRC (C).
Figure 4
Figure 4
AMPD2 levels are significantly increased in primary colorectal cancer (CRC) tissues compared with precancerous tissue using 15 pairs of fresh CRC/precancerous tissue. Data are expressed as the Mean ± SD. Statistical analysis was conducted using Student’s t test.
Figure 5
Figure 5
Expression of AMPD2 in colon adenocarcinoma (COAD), rectum adenocarcinoma (READ), breast invasive carcinoma (BRCA), cholangiocarcinoma (CHOL), and liver hepatocellular carcinoma (LIHC) are plotted for both tumor and normal tissues (TCGA dataset). Expression values of mRNAs are log2-transformed (A). Kaplan-Meier plots for overall survival for a discriminatory median AMPD2 expression, from TCGA sequencing data to assess prognostic accuracy. P values were calculated using the log-rank test and Gehan-Breslow-Wilcoxon test (B).

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