Literature DB >> 31848187

The Proteomic Landscape of Pancreatic Ductal Adenocarcinoma Liver Metastases Identifies Molecular Subtypes and Associations with Clinical Response.

Henry C-H Law1, Dragana Lagundžin1, Emalie J Clement1, Fangfang Qiao1, Zachary S Wagner1, Kimiko L Krieger1, Diane Costanzo-Garvey2, Thomas C Caffrey1, Jean L Grem3, Dominick J DiMaio2, Paul M Grandgenett1, Leah M Cook2, Kurt W Fisher2, Fang Yu4, Michael A Hollingsworth1, Nicholas T Woods5.   

Abstract

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease that can be separated into distinct subtypes based on molecular signatures. Identifying PDAC subtype-specific therapeutic vulnerabilities is necessary to develop precision medicine approaches to treat PDAC. EXPERIMENTAL
DESIGN: A total of 56 PDAC liver metastases were obtained from the UNMC Rapid Autopsy Program and analyzed with quantitative proteomics. PDAC subtypes were identified by principal component analysis based on protein expression profiling. Proteomic subtypes were further characterized by the associated clinical information, including but not limited to survival analysis, drug treatment response, and smoking and drinking status.
RESULTS: Over 3,960 proteins were identified and used to delineate four distinct PDAC microenvironment subtypes: (i) metabolic; (ii) progenitor-like; (iii) proliferative; and (iv) inflammatory. PDAC risk factors of alcohol and tobacco consumption correlate with subtype classifications. Enhanced survival is observed in FOLFIRINOX treated metabolic and progenitor-like subtypes compared with the proliferative and inflammatory subtypes. In addition, TYMP, PDCD6IP, ERAP1, and STMN showed significant association with patient survival in a subtype-specific manner. Gemcitabine-induced alterations in the proteome identify proteins, such as serine hydroxymethyltransferase 1, associated with drug resistance.
CONCLUSIONS: These data demonstrate that proteomic analysis of clinical PDAC liver metastases can identify molecular signatures unique to disease subtypes and point to opportunities for therapeutic development to improve the treatment of PDAC. ©2019 American Association for Cancer Research.

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Year:  2019        PMID： 31848187      PMCID： PMC7056493          DOI： 10.1158/1078-0432.CCR-19-1496

Source DB:  PubMed          Journal:  Clin Cancer Res        ISSN： 1078-0432            Impact factor:   12.531


  50 in total

1.  FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer.

Authors:  Thierry Conroy; Pascal Hammel; Mohamed Hebbar; Meher Ben Abdelghani; Alice C Wei; Jean-Luc Raoul; Laurence Choné; Eric Francois; Pascal Artru; James J Biagi; Thierry Lecomte; Eric Assenat; Roger Faroux; Marc Ychou; Julien Volet; Alain Sauvanet; Gilles Breysacher; Frédéric Di Fiore; Christine Cripps; Petr Kavan; Patrick Texereau; Karine Bouhier-Leporrier; Faiza Khemissa-Akouz; Jean-Louis Legoux; Béata Juzyna; Sophie Gourgou; Christopher J O'Callaghan; Claire Jouffroy-Zeller; Patrick Rat; David Malka; Florence Castan; Jean-Baptiste Bachet
Journal:  N Engl J Med       Date:  2018-12-20       Impact factor: 91.245

2.  FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer.

Authors:  Thierry Conroy; Françoise Desseigne; Marc Ychou; Olivier Bouché; Rosine Guimbaud; Yves Bécouarn; Antoine Adenis; Jean-Luc Raoul; Sophie Gourgou-Bourgade; Christelle de la Fouchardière; Jaafar Bennouna; Jean-Baptiste Bachet; Faiza Khemissa-Akouz; Denis Péré-Vergé; Catherine Delbaldo; Eric Assenat; Bruno Chauffert; Pierre Michel; Christine Montoto-Grillot; Michel Ducreux
Journal:  N Engl J Med       Date:  2011-05-12       Impact factor: 91.245

3.  Genomics-Driven Precision Medicine for Advanced Pancreatic Cancer: Early Results from the COMPASS Trial.

Authors:  Kyaw L Aung; Sandra E Fischer; Robert E Denroche; Gun-Ho Jang; Anna Dodd; Sean Creighton; Bernadette Southwood; Sheng-Ben Liang; Dianne Chadwick; Amy Zhang; Grainne M O'Kane; Hamzeh Albaba; Shari Moura; Robert C Grant; Jessica K Miller; Faridah Mbabaali; Danielle Pasternack; Ilinca M Lungu; John M S Bartlett; Sangeet Ghai; Mathieu Lemire; Spring Holter; Ashton A Connor; Richard A Moffitt; Jen Jen Yeh; Lee Timms; Paul M Krzyzanowski; Neesha Dhani; David Hedley; Faiyaz Notta; Julie M Wilson; Malcolm J Moore; Steven Gallinger; Jennifer J Knox
Journal:  Clin Cancer Res       Date:  2017-12-29       Impact factor: 12.531

4.  Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine.

Authors:  Andrew J Aguirre; Jonathan A Nowak; Nicholas D Camarda; Richard A Moffitt; Arezou A Ghazani; Mehlika Hazar-Rethinam; Srivatsan Raghavan; Jaegil Kim; Lauren K Brais; Dorisanne Ragon; Marisa W Welch; Emma Reilly; Devin McCabe; Lori Marini; Kristin Anderka; Karla Helvie; Nelly Oliver; Ana Babic; Annacarolina Da Silva; Brandon Nadres; Emily E Van Seventer; Heather A Shahzade; Joseph P St Pierre; Kelly P Burke; Thomas Clancy; James M Cleary; Leona A Doyle; Kunal Jajoo; Nadine J McCleary; Jeffrey A Meyerhardt; Janet E Murphy; Kimmie Ng; Anuj K Patel; Kimberly Perez; Michael H Rosenthal; Douglas A Rubinson; Marvin Ryou; Geoffrey I Shapiro; Ewa Sicinska; Stuart G Silverman; Rebecca J Nagy; Richard B Lanman; Deborah Knoerzer; Dean J Welsch; Matthew B Yurgelun; Charles S Fuchs; Levi A Garraway; Gad Getz; Jason L Hornick; Bruce E Johnson; Matthew H Kulke; Robert J Mayer; Jeffrey W Miller; Paul B Shyn; David A Tuveson; Nikhil Wagle; Jen Jen Yeh; William C Hahn; Ryan B Corcoran; Scott L Carter; Brian M Wolpin
Journal:  Cancer Discov       Date:  2018-06-14       Impact factor: 39.397

5.  Pathobiological implications of MUC16 expression in pancreatic cancer.

Authors:  Dhanya Haridas; Subhankar Chakraborty; Moorthy P Ponnusamy; Imayavaramban Lakshmanan; Satyanarayana Rachagani; Eric Cruz; Sushil Kumar; Srustidhar Das; Subodh M Lele; Judy M Anderson; Uwe A Wittel; Michael A Hollingsworth; Surinder K Batra
Journal:  PLoS One       Date:  2011-10-31       Impact factor: 3.240

6.  Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy.

Authors:  Eric A Collisson; Anguraj Sadanandam; Peter Olson; William J Gibb; Morgan Truitt; Shenda Gu; Janine Cooc; Jennifer Weinkle; Grace E Kim; Lakshmi Jakkula; Heidi S Feiler; Andrew H Ko; Adam B Olshen; Kathleen L Danenberg; Margaret A Tempero; Paul T Spellman; Douglas Hanahan; Joe W Gray
Journal:  Nat Med       Date:  2011-04-03       Impact factor: 53.440

7.  Proteins associated with pancreatic cancer survival in patients with resectable pancreatic ductal adenocarcinoma.

Authors:  Ru Chen; David W Dawson; Sheng Pan; Niki A Ottenhof; Roeland F de Wilde; Christopher L Wolfgang; Damon H May; David A Crispin; Lisa A Lai; Anna R Lay; Meghna Waghray; Shouli Wang; Martin W McIntosh; Diane M Simeone; Anirban Maitra; Teresa A Brentnall
Journal:  Lab Invest       Date:  2014-10-27       Impact factor: 5.662

Review 8.  Chemotherapy and tumor microenvironment of pancreatic cancer.

Authors:  Qiaofei Liu; Quan Liao; Yupei Zhao
Journal:  Cancer Cell Int       Date:  2017-07-05       Impact factor: 5.722

9.  Three Dimensional Mixed-Cell Spheroids Mimic Stroma-Mediated Chemoresistance and Invasive Migration in hepatocellular carcinoma.

Authors:  Iftikhar Ali Khawar; Jong Kook Park; Eun Sun Jung; Myung Ah Lee; Suhwan Chang; Hyo-Jeong Kuh
Journal:  Neoplasia       Date:  2018-07-04       Impact factor: 5.715

10.  ALIX Regulates Tumor-Mediated Immunosuppression by Controlling EGFR Activity and PD-L1 Presentation.

Authors:  James Monypenny; Hanna Milewicz; Fabian Flores-Borja; Gregory Weitsman; Anthony Cheung; Ruhe Chowdhury; Thomas Burgoyne; Appitha Arulappu; Katherine Lawler; Paul R Barber; Jose M Vicencio; Melanie Keppler; Wahyu Wulaningsih; Sean M Davidson; Franca Fraternali; Natalie Woodman; Mark Turmaine; Cheryl Gillett; Dafne Franz; Sergio A Quezada; Clare E Futter; Alex Von Kriegsheim; Walter Kolch; Borivoj Vojnovic; Jeremy G Carlton; Tony Ng
Journal:  Cell Rep       Date:  2018-07-17       Impact factor: 9.423
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  13 in total

1.  The limits of molecular signatures for pancreatic ductal adenocarcinoma subtyping.

Authors:  Manuela Lautizi; Jan Baumbach; Wilko Weichert; Katja Steiger; Markus List; Nicole Pfarr; Tim Kacprowski
Journal:  NAR Cancer       Date:  2022-10-17

2.  Neoplastic cell enrichment of tumor tissues using coring and laser microdissection for proteomic and genomic analyses of pancreatic ductal adenocarcinoma.

Authors:  Qing Kay Li; Yingwei Hu; Lijun Chen; Michael Schnaubelt; Daniel Cui Zhou; Yize Li; Rita Jui-Hsien Lu; Mathangi Thiagarajan; Galen Hostetter; Chelsea J Newton; Scott D Jewell; Gil Omenn; Ana I Robles; Mehdi Mesri; Oliver F Bathe; Bing Zhang; Li Ding; Ralph H Hruban; Daniel W Chan; Hui Zhang
Journal:  Clin Proteomics       Date:  2022-10-20       Impact factor: 5.000

3.  Small-molecule IKKβ activation modulator (IKAM) targets MAP3K1 and inhibits pancreatic tumor growth.

Authors:  John Victor Napoleon; Satish Sagar; Sydney P Kubica; Lidia Boghean; Smit Kour; Hannah M King; Yogesh A Sonawane; Ayrianne J Crawford; Nagsen Gautam; Smitha Kizhake; Pawel A Bialk; Eric Kmiec; Jayapal Reddy Mallareddy; Prathamesh P Patil; Sandeep Rana; Sarbjit Singh; Janani Prahlad; Paul M Grandgenett; Gloria E O Borgstahl; Gargi Ghosal; Yazen Alnouti; Michael A Hollingsworth; Prakash Radhakrishnan; Amarnath Natarajan
Journal:  Proc Natl Acad Sci U S A       Date:  2022-04-27       Impact factor: 12.779

4.  The Proteomic Landscape of Pancreatic Ductal Adenocarcinoma Liver Metastases Identifies Molecular Subtypes and Associations with Clinical Response-Response.

Authors:  Henry C-H Law; Emalie J Clement; Paul M Grandgenett; Michael A Hollingsworth; Nicholas T Woods
Journal:  Clin Cancer Res       Date:  2021-07-15       Impact factor: 12.531

5.  Data-Driven Computational Modeling Identifies Determinants of Glioblastoma Response to SHP2 Inhibition.

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Review 6.  The role of tumor heterogeneity in immune-tumor interactions.

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Journal:  Cancer Metastasis Rev       Date:  2021-03-08       Impact factor: 9.237

7.  Combined Alcohol Exposure and KRAS Mutation in Human Pancreatic Ductal Epithelial Cells Induces Proliferation and Alters Subtype Signatures Determined by Multi-Omics Analysis.

Authors:  Emalie J Clement; Henry C-H Law; Fangfang Qiao; Dragana Noe; Jose G Trevino; Nicholas T Woods
Journal:  Cancers (Basel)       Date:  2022-04-13       Impact factor: 6.639

8.  Prognostic value of biomarkers in the tumor microenvironment of pancreatic ductal adenocarcinoma.

Authors:  Nitish K Mishra; Siddesh Southekal; Chittibabu Guda
Journal:  Ann Transl Med       Date:  2020-05

Review 9.  Current Strategies and Future Perspectives for Precision Medicine in Pancreatic Cancer.

Authors:  Ivonne Regel; Julia Mayerle; Ujjwal Mukund Mahajan
Journal:  Cancers (Basel)       Date:  2020-04-21       Impact factor: 6.639

Review 10.  The molecular biology of pancreatic adenocarcinoma: translational challenges and clinical perspectives.

Authors:  Shun Wang; Yan Zheng; Feng Yang; Le Zhu; Xiao-Qiang Zhu; Zhe-Fang Wang; Xiao-Lin Wu; Cheng-Hui Zhou; Jia-Yan Yan; Bei-Yuan Hu; Bo Kong; De-Liang Fu; Christiane Bruns; Yue Zhao; Lun-Xiu Qin; Qiong-Zhu Dong
Journal:  Signal Transduct Target Ther       Date:  2021-07-05
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