Neoadjuvant chemo- or chemo-radiation-therapy of pancreatic ductal adenocarcinoma differentially shift ECM composition, complement activation, energy metabolism and ribosomal proteins of the residual tumor mass.
data-independent acquisition
mass spectrometry
neoadjuvant therapy
pancreatic ductal adenocarcinoma
proteogenomics
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
14 Feb 2024
14 Feb 2024
Historique:
revised:
08
11
2023
received:
21
08
2023
accepted:
20
12
2023
medline:
14
2
2024
pubmed:
14
2
2024
entrez:
14
2
2024
Statut:
aheadofprint
Résumé
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, often diagnosed at stages that dis-qualify for surgical resection. Neoadjuvant therapies offer potential tumor regression and improved resectability. Although features of the tumor biology (e.g., molecular markers) may guide adjuvant therapy, biological alterations after neoadjuvant therapy remain largely unexplored. We performed mass spectrometry to characterize the proteomes of 67 PDAC resection specimens of patients who received either neoadjuvant chemo (NCT) or chemo-radiation (NCRT) therapy. We employed data-independent acquisition (DIA), yielding a proteome coverage in excess of 3500 proteins. Moreover, we successfully integrated two publicly available proteome datasets of treatment-naïve PDAC to unravel proteome alterations in response to neoadjuvant therapy, highlighting the feasibility of this approach. We found highly distinguishable proteome profiles. Treatment-naïve PDAC was characterized by enrichment of immunoglobulins, complement and extracellular matrix (ECM) proteins. Post-NCT and post-NCRT PDAC presented high abundance of ribosomal and metabolic proteins as compared to treatment-naïve PDAC. Further analyses on patient survival and protein expression identified treatment-specific prognostic candidates. We present the first proteomic characterization of the residual PDAC mass after NCT and NCRT, and potential protein candidate markers associated with overall survival. We conclude that residual PDAC exhibits fundamentally different proteome profiles as compared to treatment-naïve PDAC, influenced by the type of neoadjuvant treatment. These findings may impact adjuvant or targeted therapy options.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : German Consortium for Translational Cancer Research project (Impro-Rec)
Organisme : investBW program
ID : BW1_1198/03
Organisme : Deutsche Forschungsgemeinschaft
ID : 322977937
Organisme : Deutsche Forschungsgemeinschaft
ID : 405351425
Organisme : Deutsche Forschungsgemeinschaft
ID : 423813989
Organisme : Deutsche Forschungsgemeinschaft
ID : 431336276
Organisme : Deutsche Forschungsgemeinschaft
ID : 43198400
Organisme : Deutsche Forschungsgemeinschaft
ID : 441891347
Organisme : Deutsche Forschungsgemeinschaft
ID : 444936968
Organisme : Deutsche Forschungsgemeinschaft
ID : 446058856
Organisme : Deutsche Forschungsgemeinschaft
ID : 466359513
Organisme : ERA PerMed program (BMBF)
ID : 01KU1915A
Organisme : ERA PerMed program (BMBF)
ID : 01KU1916
Organisme : ERA TransCan program "PREDICO"
ID : 01KT2201
Organisme : Mushett Family Foundation (MSKCC-Freiburg project)
Informations de copyright
© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
Références
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7-33.
Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913-2921.
Hackert T, Ulrich A, Büchler MW. Can neoadjuvant therapy in pancreatic cancer increase the Pool of patients eligible for pancreaticoduodenectomy? Adv Surg. 2017;51(1):1-10.
Klaiber U, Leonhardt CS, Strobel O, Tjaden C, Hackert T, Neoptolemos JP. Neoadjuvant and adjuvant chemotherapy in pancreatic cancer. Langenbecks Arch Surg. 2018;403(8):917-932.
Adamska A, Elaskalani O, Emmanouilidi A, et al. Molecular and cellular mechanisms of chemoresistance in pancreatic cancer. Adv Biol Regul. 2018;68:77-87.
Bittoni A, Santoni M, Lanese A, Pellei C, Andrikou K, Stefano C. Neoadjuvant therapy in pancreatic cancer: An emerging strategy. Gastroenterol Res Pract. 2014;2014:183852.
Chopra A, Hodges JC, Olson A, et al. Outcomes of neoadjuvant chemotherapy versus chemoradiation in localized pancreatic cancer: a case-control matched analysis. Ann Surg Oncol. 2021;28(7):3779-3788.
Gillen S, Schuster T, Meyer Zum Büschenfelde C, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010;7(4):e1000267.
Townend P, de Reuver PR, Chua TC, et al. Histopathological tumour viability after neoadjuvant chemotherapy influences survival in resected pancreatic cancer: analysis of early outcome data. ANZ J Surg. 2018;88(3):E167-E172.
Sahni S, Nahm C, Krisp C, et al. Identification of novel biomarkers in pancreatic tumor tissue to predict response to neoadjuvant chemotherapy. Front Oncol. 2020;4(10):237.
O'Rourke MB, Sahni S, Samra J, Mittal A, Molloy MP. Data independent acquisition of plasma biomarkers of response to neoadjuvant chemotherapy in pancreatic ductal adenocarcinoma. J Proteomics. 2021;16(231):103998.
Amrutkar M, Verbeke CS, Finstadsveen AV, Dorg L, Labori KJ, Gladhaug IP. Neoadjuvant chemotherapy is associated with an altered metabolic profile and increased cancer stemness in patients with pancreatic ductal adenocarcinoma. Mol Oncol. 2022;17(1):1878-0261.13344.
Dias Costa A, Väyrynen SA, Chawla A, et al. Neoadjuvant chemotherapy is associated with altered immune cell infiltration and an anti-tumorigenic microenvironment in resected pancreatic cancer. Clin Cancer Res. 2022;28(23):5167-5179.
Werner J, Bernhard P, Cosenza-Contreras M, et al. Targeted and explorative profiling of kallikrein proteases and global proteome biology of pancreatic ductal adenocarcinoma, chronic pancreatitis, and normal pancreas highlights disease-specific proteome remodelling. Neoplasia. 2023;36:100871.
Sadot E, Doussot A, O'Reilly EM, et al. FOLFIRINOX induction therapy for Stage 3 pancreatic adenocarcinoma. Ann Surg Oncol. 2015;22(11):3512-3521.
Föll MC, Fahrner M, Oria VO, et al. Reproducible proteomics sample preparation for single FFPE tissue slices using acid-labile surfactant and direct trypsinization. Clin Proteomics. 2018;15(1):11.
Demichev V, Messner CB, Vernardis SI, Lilley KS, Ralser M. DIA-NN: neural networks and interference correction enable deep proteome coverage in high throughput. Nat Methods. 2020;17(1):41-44.
R Core Team. R: A Language and Environment for Statistical Computing [Internet]. Vienna, Austria: R Foundation for Statistical Computing. 2022 https://www.R-project.org/
Ellis MJ, Gillette M, Carr SA, et al. Connecting genomic alterations to cancer biology with proteomics: the NCI clinical proteomic tumor analysis consortium. Cancer Discov. 2013;3(10):1108-1112.
Johnson WE, Li C, Rabinovic A. Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2007;8(1):118-127.
Egert J, Brombacher E, Warscheid B, Kreutz C. DIMA: data-driven selection of an imputation algorithm. J Proteome Res. 2021;20(7):3489-3496.
Hong SM, Goggins M, Wolfgang CL, et al. Vascular invasion in infiltrating ductal adenocarcinoma of the pancreas can mimic pancreatic intraepithelial neoplasia: a histopathologic study of 209 cases. Am J Surg Pathol. 2012;36(2):235-241.
Karachaliou GS, Lazarou V, Giannis D, Astras G, Moris D, Petrou A. Initial experience with neoadjuvant FOLFIRINOX as first line therapy for locally advanced pancreatic cancer. J BUON off J Balk Union Oncol. 2020;25(5):2525-2527.
Itchins M, Arena J, Nahm CB, et al. Retrospective cohort analysis of neoadjuvant treatment and survival in resectable and borderline resectable pancreatic ductal adenocarcinoma in a high volume referral centre. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol. 2017;43(9):1711-1717.
Fröhlich K, Brombacher E, Fahrner M, et al. Benchmarking of analysis strategies for data-independent acquisition proteomics using a large-scale dataset comprising inter-patient heterogeneity. Nat Commun. 2022;13(1):2622.
Cao L, Huang C, Cui Zhou D, et al. Proteogenomic characterization of pancreatic ductal adenocarcinoma. Cell. 2021;184(19):5031-5052.e26.
Oria VO, Bronsert P, Thomsen AR, et al. Proteome profiling of primary pancreatic ductal adenocarcinomas undergoing additive chemoradiation link ALDH1A1 to early local recurrence and chemoradiation resistance. Transl Oncol. 2018;11(6):1307-1322.
Farshadi EA, Chang J, Sampadi B, et al. Organoids derived from neoadjuvant FOLFIRINOX patients recapitulate therapy resistance in pancreatic ductal adenocarcinoma. Clin Cancer Res. 2021;27(23):6602-6612.
Clark DW, Palle K. Aldehyde dehydrogenases in cancer stem cells: potential as therapeutic targets. Ann Transl Med. 2016;4(24):518.
Jamieson NB, Carter CR, McKay CJ, Oien KA. Tissue biomarkers for prognosis in pancreatic ductal adenocarcinoma: a systematic review and meta-analysis. Clin Cancer Res. 2011;17(10):3316-3331.
Ohuchida K, Mizumoto K, Miyasaka Y, et al. Over-expression of S100A2 in pancreatic cancer correlates with progression and poor prognosis. J Pathol. 2007;213(3):275-282.
Lin H, Yang P, Li B, et al. S100A10 promotes pancreatic ductal adenocarcinoma cells proliferation, migration and adhesion through JNK/LAMB3-LAMC2 Axis. Cancer. 2022;15(1):202.
Wilson DN, Doudna Cate JH. The structure and function of the eukaryotic ribosome. Cold Spring Harb Perspect Biol. 2012;4(5):a011536.
McDonald OG. The biology of pancreatic cancer morphology. Pathology (Phila). 2022;54(2):236-247.
Nakajima K, Ino Y, Naito C, et al. Neoadjuvant therapy alters the collagen architecture of pancreatic cancer tissue via ephrin-A5. Br J Cancer. 2022;126(4):628-639.
Dangi-Garimella S, Krantz SB, Barron MR, et al. Three-dimensional collagen I promotes gemcitabine resistance in pancreatic cancer through MT1-MMP-mediated expression of HMGA2. Cancer Res. 2011;71(3):1019-1028.
Iacobuzio-Donahue CA, Ryu B, Hruban RH, Kern SE. Exploring the host desmoplastic response to pancreatic carcinoma. Am J Pathol. 2002;160(1):91-99.
Zhou X, An J, Kurilov R, et al. Persister cell phenotypes contribute to poor patient outcomes after neoadjuvant chemotherapy in PDAC. Nat Cancer. 2023;4(9):1362-1381.
Mueller AC, Piper M, Goodspeed A, et al. Induction of ADAM10 by RT drives fibrosis, resistance, and EMT in pancreatic cancer. Cancer Res. 2021;81(12):3255-3269.
Farren MR, Sayegh L, Ware MB, et al. Immunologic alterations in the pancreatic cancer microenvironment of patients treated with neoadjuvant chemotherapy and radiotherapy. JCI Insight. 2020;5(1):130362.
Rutkowski MJ, Sughrue ME, Kane AJ, Mills SA, Parsa AT. Cancer and the complement cascade. Mol Cancer Res MCR. 2010;8(11):1453-1465.
Mamidi S, Höne S, Kirschfink M. The complement system in cancer: ambivalence between tumour destruction and promotion. Immunobiology. 2017;222(1):45-54.
Roumenina LT, Daugan MV, Petitprez F, Sautès-Fridman C, Fridman WH. Context-dependent roles of complement in cancer. Nat Rev Cancer. 2019;19(12):698-715.
Melmer A, Fineder L, Lamina C, et al. Plasma concentrations of the vitamin E-binding protein afamin are associated with overall and progression-free survival and platinum sensitivity in serous ovarian cancer: a study by the OVCAD consortium. Gynecol Oncol. 2013;128(1):38-43.
Humphries JM, Penno MAS, Weiland F, et al. Identification and validation of novel candidate protein biomarkers for the detection of human gastric cancer. Biochim Biophys Acta BBA - Proteins Proteom. 2014;1844(5):1051-1058.
de Freitas Chama LL, Ebstein F, Wiesrecker B, et al. Immunoproteasome impairment via β5i/LMP7-deletion leads to sustained pancreatic injury from experimental pancreatitis. J Cell Mol Med. 2021;25(14):6786-6799.
Dunn TA, Chen S, Faith DA, et al. A novel role of myosin VI in human prostate cancer. Am J Pathol. 2006;169(5):1843-1854.
Naora H, Montell DJ. Ovarian cancer metastasis: integrating insights from disparate model organisms. Nat Rev Cancer. 2005;5(5):355-366.
Droeser RA, Hirt C, Eppenberger-Castori S, et al. High myeloperoxidase positive cell infiltration in colorectal cancer is an independent favorable prognostic factor. PLoS One. 2013;8(5):e64814.
Zeindler J, Angehrn F, Droeser R, et al. Infiltration by myeloperoxidase-positive neutrophils is an independent prognostic factor in breast cancer. Breast Cancer Res Treat. 2019;177(3):581-589.