Decreased copy number of mitochondrial DNA: A potential diagnostic criterion for gastric cancer

Abstract

An alteration in the mitochondrial DNA (mtDNA) copy number has been detected in numerous human cancers. However, certain changes in the mtDNA copy number that occur during the initiation and progression of gastric cancer remain undetected. In the present study, using quantitative PCR analysis, the quantitative changes in mtDNA were observed during the initiation and progression of gastric cancer. Furthermore, the possible correlation between the changes in mtDNA and the clinicopathological stage were also investigated. However, the mechanism by which the change in mtDNA copy number occurs remains to be elucidated. Epigenetic changes are believed to play a significant role in regulating the mtDNA content. In order to determine whether there is a potential correlation between DNA methylation and mtDNA regulation, in vitro demethylation experiments were performed. Tumor tissues and corresponding non-cancerous tissues were surgically resected from 76 gastric cancer patients between 2010 and 2011. The results revealed that the average relative mtDNA copy numbers were 94.71±28.11 in the cancer tissues and 111.68±21.84 in the corresponding non-cancerous tissues (P<0.01). The quantitative changes in mtDNA demonstrated a significant decrease in gastric cancer, particularly in ill-defined stage III and IV cases, but had no association with gender. The mtDNA copy numbers demonstrated a marked increase (P<0.05) following demethylation treatment. The present results indicate that the mtDNA copy number plays a significant role during the progression of colorectal cancer, particularly during the late clinicopathological stages, and that the change in the mtDNA copy number may correlate with DNA methylation.

Keywords: clinicopathological stage; copy number; gastric cancer; mitochondrial DNA.

Figure 1

(A) Comparison of the relative mtDNA copy number between gastric cancer tissues and corresponding non-cancerous tissues of each case. (B) Comparison of the average relative mtDNA copy number between 76 gastric cancer tissues and the corresponding non-cancerous tissues. The mtDNA copy number of the tumor tissues was significantly higher than that of the corresponding non-cancerous tissues (^*P<0.05). (C) Comparison of the average relative mtDNA copy numbers of 76 gastric cancer tissues and the corresponding non-cancerous tissues between genders. The mtDNA copy number of the tumor tissues showed no significant difference (P=0.621). In the corresponding non-cancerous tissues, there was also no significant difference (P=0.478). mtDNA, mitochondrial DNA

Figure 2

Average relative mtDNA copy number of gastric cancer of each clinicopathological stage I–IV. (^*P<0.05). mtDNA, mitochondrial DNA.

Figure 3

Relative mtDNA copy number of gastric mucosa cells prior to and following 5-Aza treatment. (^*P<0.05). mtDNA, mitochondrial DNA; 5-Aza, 5-Aza-2′-deoxycytidine.