CT radiomics associations with genotype and stromal content in pancreatic ductal adenocarcinoma

被引：53

作者：

Attiyeh, Marc A. ^{[1
]}

Chakraborty, Jayasree ^{[1
]}

McIntyre, Caitlin A. ^{[1
]}

Kappagantula, Rajya ^{[2
]}

Chou, Yuting ^{[1
]}

Askan, Gokce ^{[2
]}

Seier, Kenneth ^{[3
]}

Gonen, Mithat ^{[3
]}

Basturk, Olca ^{[2
]}

Balachandran, Vinod P. ^{[1
]}

Kingham, T. Peter ^{[1
]}

D'Angelica, Michael I. ^{[1
]}

Drebin, Jeffrey A. ^{[1
]}

Jarnagin, William R. ^{[1
]}

Allen, Peter J. ^{[1
]}

Iacobuzio-Donahue, Christine A. ^{[2
]}

Simpson, Amber L. ^{[1
]}

Do, Richard K. ^{[4
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Pathol, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA

[3] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA

[4] Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave,C-276F, New York, NY 10065 USA

来源：

ABDOMINAL RADIOLOGY | 2019年 / 44卷 / 09期

基金：

美国国家卫生研究院;

关键词：

Pancreatic neoplasm; Computational biology; Survival; Radiogenomics; Genomics; CANCER; MUTATIONS; CARCINOMA; SURVIVAL; GENE; PROGNOSIS; PATHWAY; BURDEN;

D O I：

10.1007/s00261-019-02112-1

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

1002 ; 100207 ; 1009 ;

摘要：

Purpose The aim of this study was to investigate the relationship between CT imaging phenotypes and genetic and biological characteristics in pancreatic ductal adenocarcinoma (PDAC). Methods In this retrospective study, consecutive patients between April 2015 and June 2016 who underwent PDAC resection were included if previously consented to a targeted sequencing protocol. Mutation status of known PDAC driver genes (KRAS, TP53, CDKN2A, and SMAD4) in the primary tumor was determined by targeted DNA sequencing and results were validated by immunohistochemistry (IHC). Radiomic features of the tumor were extracted from the preoperative CT scan and used to predict genotype and stromal content. Results The cohort for analysis consisted of 35 patients. Genomic and IHC analysis revealed alterations in KRAS in 34 (97%) patients, and changes in expression of CDKN2A in 29 (83%), SMAD4 in 16 (46%), and in TP53 in 29 (83%) patients. Models created from radiomic features demonstrated associations with SMAD4 status and the number of genes altered. The number of genes altered was the only significant predictor of overall survival (p = 0.016). By linear regression analysis, a prediction model for stromal content achieved an R-2 value of 0.731 with a root mean square error of 19.5. Conclusions In this study, we demonstrate that in PDAC SMAD4 status and tumor stromal content can be predicted using radiomic analysis of preoperative CT imaging. These data show an association between resectable PDAC imaging features and underlying tumor biology and their potential for future precision medicine.

引用

页码：3148 / 3157

页数：10

共 36 条

[1] Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach [J].

Aerts, Hugo J. W. L. ;

Velazquez, Emmanuel Rios ;

Leijenaar, Ralph T. H. ;

Parmar, Chintan ;

Grossmann, Patrick ;

Cavalho, Sara ;

Bussink, Johan ;

Monshouwer, Rene ;

Haibe-Kains, Benjamin ;

Rietveld, Derek ;

Hoebers, Frank ;

Rietbergen, Michelle M. ;

Leemans, C. Rene ;

Dekker, Andre ;

Quackenbush, John ;

Gillies, Robert J. ;

Lambin, Philippe .

NATURE COMMUNICATIONS, 2014, 5

[2] MOST HUMAN CARCINOMAS OF THE EXOCRINE PANCREAS CONTAIN MUTANT C-K-RAS GENES [J].

ALMOGUERA, C ;

SHIBATA, D ;

FORRESTER, K ;

MARTIN, J ;

ARNHEIM, N ;

PERUCHO, M .

CELL, 1988, 53 (04) :549-554

[3] Survival Prediction in Pancreatic Ductal Adenocarcinoma by Quantitative Computed Tomography Image Analysis [J].

Attiyeh, Marc A. ;

Chakraborty, Jayasree ;

Doussot, Alexandre ;

Langdon-Embry, Liana ;

Mainarich, Shiana ;

Gonen, Mithat ;

Balachandran, Vinod P. ;

D'Angelica, Michael I. ;

DeMatteo, Ronald P. ;

Jarnagin, William R. ;

Kingham, T. Peter ;

Allen, Peter J. ;

Simpson, Amber L. ;

Do, Richard K. .

ANNALS OF SURGICAL ONCOLOGY, 2018, 25 (04) :1034-1042

[4] Genomic analyses identify molecular subtypes of pancreatic cancer [J].

Bailey, Peter ;

Chang, David K. ;

Nones, Katia ;

Johns, Amber L. ;

Patch, Ann-Marie ;

Gingras, Marie-Claude ;

Miller, David K. ;

Christ, Angelika N. ;

Bruxner, Tim J. C. ;

Quinn, Michael C. ;

Nourse, Craig ;

Murtaugh, L. Charles ;

Harliwong, Ivon ;

Idrisoglu, Senel ;

Manning, Suzanne ;

Nourbakhsh, Ehsan ;

Wani, Shivangi ;

Fink, Lynn ;

Holmes, Oliver ;

Chin, Vencssa ;

Anderson, Matthew J. ;

Kazakoff, Stephen ;

Leonard, Conrad ;

Newell, Felicity ;

Waddell, Nick ;

Wood, Scott ;

Xu, Qinying ;

Wilson, Peter J. ;

Cloonan, Nicole ;

Kassahn, Karin S. ;

Taylor, Darrin ;

Quek, Kelly ;

Robertson, Alan ;

Pantano, Lorena ;

Mincarelli, Laura ;

Sanchez, Luis N. ;

Evers, Lisa ;

Wu, Jianmin ;

Pinese, Mark ;

Cowley, Mark J. ;

Jones, Marc D. ;

Colvin, Emily K. ;

Nagrial, Adnan M. ;

Humphrey, Emily S. ;

Chantrill, Lorraine A. ;

Mawson, Amanda ;

Humphris, Jeremy ;

Chou, Angela ;

Pajic, Marina ;

Scarlett, Christopher J. .

NATURE, 2016, 531 (7592) :47-+

[5] Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes [J].

Biankin, Andrew V. ;

Waddell, Nicola ;

Kassahn, Karin S. ;

Gingras, Marie-Claude ;

Muthuswamy, Lakshmi B. ;

Johns, Amber L. ;

Miller, David K. ;

Wilson, Peter J. ;

Patch, Ann-Marie ;

Wu, Jianmin ;

Chang, David K. ;

Cowley, Mark J. ;

Gardiner, Brooke B. ;

Song, Sarah ;

Harliwong, Ivon ;

Idrisoglu, Senel ;

Nourse, Craig ;

Nourbakhsh, Ehsan ;

Manning, Suzanne ;

Wani, Shivangi ;

Gongora, Milena ;

Pajic, Marina ;

Scarlett, Christopher J. ;

Gill, Anthony J. ;

Pinho, Andreia V. ;

Rooman, Ilse ;

Anderson, Matthew ;

Holmes, Oliver ;

Leonard, Conrad ;

Taylor, Darrin ;

Wood, Scott ;

Xu, Qinying ;

Nones, Katia ;

Fink, J. Lynn ;

Christ, Angelika ;

Bruxner, Tim ;

Cloonan, Nicole ;

Kolle, Gabriel ;

Newell, Felicity ;

Pinese, Mark ;

Mead, R. Scott ;

Humphris, Jeremy L. ;

Kaplan, Warren ;

Jones, Marc D. ;

Colvin, Emily K. ;

Nagrial, Adnan M. ;

Humphrey, Emily S. ;

Chou, Angela ;

Chin, Venessa T. ;

Chantrill, Lorraine A. .

NATURE, 2012, 491 (7424) :399-405

[6] Tumor Mutation Burden Forecasts Outcome in Ovarian Cancer with BRCA1 or BRCA2 Mutations [J].

Birkbak, Nicolai Juul ;

Kochupurakkal, Bose ;

Izarzugaza, Jose M. G. ;

Eklund, Aron C. ;

Li, Yang ;

Liu, Joyce ;

Szallasi, Zoltan ;

Matulonis, Ursula A. ;

Richardson, Andrea L. ;

Iglehart, J. Dirk ;

Wang, Zhigang C. .

PLOS ONE, 2013, 8 (11)

[7] SMAD4 Gene Mutations Are Associated with Poor Prognosis in Pancreatic Cancer [J].

Blackford, Amanda ;

Serrano, Oscar K. ;

Wolfgang, Christopher L. ;

Parmigiani, Giovanni ;

Jones, Sian ;

Zhang, Xiaosong ;

Parsons, D. Williams ;

Lin, Jimmy Cheng-Ho ;

Leary, Rebecca J. ;

Eshleman, James R. ;

Goggins, Michael ;

Jaffee, Elizabeth M. ;

Iacobuzio-Donahue, Christine A. ;

Maitra, Anirban ;

Cameron, John L. ;

Olino, Kelly ;

Schulick, Richard ;

Winter, Jordan ;

Herman, Joseph M. ;

Laheru, Daniel ;

Klein, Alison P. ;

Vogelstein, Bert ;

Kinzler, Kenneth W. ;

Velculescu, Victor E. ;

Hruban, Ralph H. .

CLINICAL CANCER RESEARCH, 2009, 15 (14) :4674-4679

[8] Measurements of fractal dimension by box-counting: a critical analysis of data scatter [J].

Buczkowski, S ;

Hildgen, P ;

Cartilier, L .

PHYSICA A, 1998, 252 (1-2) :23-34

[9] FREQUENT SOMATIC MUTATIONS AND HOMOZYGOUS DELETIONS OF THE P16 (MTS1) GENE IN PANCREATIC ADENOCARCINOMA [J].

CALDAS, C ;

HAHN, SA ;

DACOSTA, LT ;

REDSTON, MS ;

SCHUTTE, M ;

SEYMOUR, AB ;

WEINSTEIN, CL ;

HRUBAN, RH ;

YEO, CJ ;

KERN, SE .

NATURE GENETICS, 1994, 8 (01) :27-32

[10] Preliminary study of tumor heterogeneity in imaging predicts two year survival in pancreatic cancer patients [J].

Chakraborty, Jayasree ;

Langdon-Embry, Liana ;

Cunanan, Kristen M. ;

Escalon, Joanna G. ;

Allen, Peter J. ;

Lowery, Maeve A. ;

O'Reilly, Eileen M. ;

Gonen, Mithat ;

Do, Richard G. ;

Simpson, Amber L. .

PLOS ONE, 2017, 12 (12)

← 1 2 3 4 →