Chen-Sung Lin1,2,3,4, Yu-Yi Huang1,5, Siao-Cian Pan6, Chia-Chuan Liu1,4, Chih-Hsun Shih1,4, Hsiang-Ling Ho7, Yi-Chen Yeh1,2,7, Teh-Ying Chou2,7, Ming-Yuan Lee1,8, Yau-Huei Wei1,2,6
1Faculty of Medicine, 2Institute of Clinical Medicine, National Yang-Ming University, Taipei;3Division of Thoracic Surgery, Feng-Yuan Hospital, Ministry of Health and Welfare, Taichung;4Division of Thoracic Surgery, 5Department of Nuclear Medicine, Koo-Foundation Sun Yat-sen Cancer Center, Taipei, Taiwan;6Center for Mitochondrial Medicine and Free Radical Research, Changhua Christian Hospital, Changhua, Taiwan;7Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan;8Department of Pathology, Koo-Foundation Sun Yat-sen Cancer Center, Taipei, Taiwan
Background: We appraised the relationship between mitochondrial DNA (mtDNA) copy number and maximum standard uptake value (SUVmax) of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan in esophageal squamous cell carcinoma (ESCC).
Methods: Forty-five ESCC patients undergoing esophagectomy in Koo-Foundation Sun Yat-sen Cancer Center were retrospectively collected. Their non-cancerous esophageal mucosa (EM) and corresponding cancerous ESCC nest were laser micro-dissected for DNA extraction. The mtDNA copy numbers of EM (mtDNAEM) and ESCC (mtDNAESCC) were analyzed by Q-PCR. The mtDNA copy ratio was defined as mtDNAESCC copy number divided by mtDNAEM copy number. Twenty-seven of the 45 ESCC patients received pre-operative FDG-PET scan, and their SUVmax of the non-cancerous esophageal background (BG, SUVmax-BG) and the corresponding cancerous ESCC nest (SUVmax-ESCC) were recorded. The SUVmax ratio was defined as SUVmax-ESCC divided by SUVmax-BG.
Results: Resection margin invasion (P<0.001), advanced T-status (T1/T2/T3/T4, P=0.035), and advanced N-status (N0/N1/N2/N3, P=0.032) were poor prognostic variables. Invasive ESCC (T2/T3/T4 vs. T1) tended to have lower mtDNAESCC copy number (P=0.001) and mtDNA copy ratio (P=0.012), but had higher SUVmax-ESCC (P<0.001) and SUVmax ratio (P=0.001). Longer ESCC tumor lengths were associated with lower mtDNAESCC copy number [correlation coefficient (CC) =−0.295, P=0.049] and mtDNA copy ratio (CC =−0.343, P=0.021), but higher SUVmax-ESCC (CC =0.513, P=0.006) and SUVmax ratio (CC =0.575, P=0.002). Furthermore, lower mtDNAESCC copy number and mtDNA copy ratio were associated with higher SUVmax-ESCC (CC =−0.448, P=0.019) and SUVmax ratio (CC =−0.563, P=0.002), respectively.
Conclusions: Decrease in the copy number and copy ratio of mtDNA with increased SUVmax-ESCC and SUVmax ratio in ESCC suggests a shift of glucose metabolism in ESCC.
Keywords: Mitochondrial DNA (mtDNA); positron emission tomography scan; glucose metabolic shift; esophageal squamous cell carcinoma (ESCC)
doi: 10.21037/jtd.2017.s002
