Gut and Liver Preoperative MTV2.5 Associated with Early Systemic Metastasis in Resected Pancreatic Cancer: A Transcriptome-Wide Analysis
Author Information
Sung Hwan Lee1,2, Ho Kyoung Hwang2,3, Woo Jung Lee2,3, Mijin Yun4, and Chang Moo Kang2,3
1Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA, 2Department of Surgery, Yonsei University College of Medicine, 3Pancreaticobiliary Cancer Clinic, Institute of Gastroenterology, Severance Hospital, and 4Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Korea

Chang Moo Kanga and Mijin Yunb
aDepartment of Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea
Tel: +82-2-2228-2100, Fax: +82-2-313-8289, E-mail: cmkang@yuhs.ac
bDepartment of Nuclear Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea
Tel: +82-2-2228-6068, Fax: +82-2-312-0578, E-mail: yunmijin@yuhs.ac
© The Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, the Korean Society of Neurogastroenterology and Motility, Korean College of Helicobacter and Upper Gastrointestinal Research, Korean Association the Study of Intestinal Diseases, the Korean Association for the Study of the Liver, Korean Pancreatobiliary Association, and Korean Society of Gastrointestinal Cancer. All rights reserved.

Abstract
Background/Aims: 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) reflects biological aggressiveness and predicts prognoses in various tumors. Evaluating the oncologic significance of the preoperative metabolic phenotype might be necessary for planning the surgical strategy in resectable pancreatic cancer. Methods: From January 2010 to December 2015, a total of 93 patients with pathologic T3 (pT3) pancreatic cancer were included in this study. Clinicopathological parameters, PET parameters, and transcriptome-wide analysis were performed to identify the oncologic impacts and molecular landscape of the metabolic phenotype of resectable pancreatic cancer. Results: Preoperative MTV2.5 was significantly higher in the pN1 group (6.5±7.8 vs 11.1±11.2, p=0.031). Higher MTV2.5 values (MTV2.5 ≥4.5) were associated with multiple lymph node metastasis (p=0.003), and the lymph node ratio was also significantly higher in resected pT3 pancreatic cancer with MTV2.5 ≥4.5 (0.05±0.08 vs 0.12±0.13, p=0.001). Disease-specific survival of patients with MTV2.5 <4.5 was better than that of patients with MTV2.5 ≥4.5 (mean, 28.8 months; 95% confidence interval [CI], 40.1 to 57.0 vs mean, 32.6 months; 95% CI, 25.5 to 39.7; p=0.026). The group of patients with MTV2.5 ≥4.5 followed by postoperative adjuvant chemotherapy showed better survival outcomes than patients with MTV2.5 ≥4.5 without adjuvant treatment in resected pT3 pancreatic cancer (p<0.001). Transcriptome-wide analysis revealed that tumors with MTV2.5 ≥4.5 demonstrated significantly different expression of cancer-related genes affecting aggressive tumor biology. Conclusions: Resectable pancreatic cancer with high MTV2.5 is not only associated with lymph node metastasis but also predicts early systemic metastasis. The molecular background of resectable pancreatic cancer with high MTV2.5 may be associated with aggressive biologic behavior, which might need to be considered when managing resectable pancreatic cancer. Further study is mandatory.
Keywords: Pancreatic neoplasms; Positron-emission tomography; Metabolic phenotype; Transcriptome-wide analysis
Abstract
Background/Aims: 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) reflects biological aggressiveness and predicts prognoses in various tumors. Evaluating the oncologic significance of the preoperative metabolic phenotype might be necessary for planning the surgical strategy in resectable pancreatic cancer. Methods: From January 2010 to December 2015, a total of 93 patients with pathologic T3 (pT3) pancreatic cancer were included in this study. Clinicopathological parameters, PET parameters, and transcriptome-wide analysis were performed to identify the oncologic impacts and molecular landscape of the metabolic phenotype of resectable pancreatic cancer. Results: Preoperative MTV2.5 was significantly higher in the pN1 group (6.5±7.8 vs 11.1±11.2, p=0.031). Higher MTV2.5 values (MTV2.5 ≥4.5) were associated with multiple lymph node metastasis (p=0.003), and the lymph node ratio was also significantly higher in resected pT3 pancreatic cancer with MTV2.5 ≥4.5 (0.05±0.08 vs 0.12±0.13, p=0.001). Disease-specific survival of patients with MTV2.5 <4.5 was better than that of patients with MTV2.5 ≥4.5 (mean, 28.8 months; 95% confidence interval [CI], 40.1 to 57.0 vs mean, 32.6 months; 95% CI, 25.5 to 39.7; p=0.026). The group of patients with MTV2.5 ≥4.5 followed by postoperative adjuvant chemotherapy showed better survival outcomes than patients with MTV2.5 ≥4.5 without adjuvant treatment in resected pT3 pancreatic cancer (p<0.001). Transcriptome-wide analysis revealed that tumors with MTV2.5 ≥4.5 demonstrated significantly different expression of cancer-related genes affecting aggressive tumor biology. Conclusions: Resectable pancreatic cancer with high MTV2.5 is not only associated with lymph node metastasis but also predicts early systemic metastasis. The molecular background of resectable pancreatic cancer with high MTV2.5 may be associated with aggressive biologic behavior, which might need to be considered when managing resectable pancreatic cancer. Further study is mandatory.
Keywords: Pancreatic neoplasms; Positron-emission tomography; Metabolic phenotype; Transcriptome-wide analysis
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