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Article: The colocatome as a spatial -omic reveals shared microenvironment features between tumour-stroma assembloids and human lung cancer.

Bouchard, Gina / Zhang, Weiruo / Li, Irene / Ilerten, Ilayda / Bhattacharya, Asmita / Li, Yuanyuan / Trope, Winston / Shrager, Joseph B / Kuo, Calvin / Tian, Lu / Giaccia, Amato J / Plevritis, Sylvia K

bioRxiv : the preprint server for biology

2023

Abstract: Computational frameworks to quantify and compare microenvironment spatial features of in-vitro patient-derived models and clinical specimens are needed. Here, we acquired and analysed multiplexed immunofluorescence images of human lung adenocarcinoma ( ... ...

Abstract	Computational frameworks to quantify and compare microenvironment spatial features of in-vitro patient-derived models and clinical specimens are needed. Here, we acquired and analysed multiplexed immunofluorescence images of human lung adenocarcinoma (LUAD) alongside tumour-stroma assembloids constructed with organoids and fibroblasts harvested from the leading edge (Tumour-Adjacent Fibroblasts;TAFs) or core (Tumour Core Fibroblasts;TCFs) of human LUAD. We introduce the concept of the "colocatome" as a spatial -omic dimension to catalogue all proximate and distant colocalisations between malignant and fibroblast subpopulations in both the assembloids and clinical specimens. The colocatome expands upon the colocalisation quotient (CLQ) through a nomalisation strategy that involves permutation analysis and thereby allows comparisons of CLQs under different conditions. Using colocatome analysis, we report that both TAFs and TCFs protected cancer cells from targeted oncogene treatment by uniquely reorganising the tumour-stroma cytoarchitecture, rather than by promoting cellular heterogeneity or selection. Moreover, we show that the assembloids' colocatome recapitulates the tumour-stroma cytoarchitecture defining the tumour microenvironment of LUAD clinical samples and thereby can serve as a functional spatial readout to guide translational discoveries.
Language	English
Publishing date	2023-09-12
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.11.557278
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Article ; Online: Galectin-1 Mediates Chronic STING Activation in Tumors to Promote Metastasis through MDSC Recruitment.

Nambiar, Dhanya K / Viswanathan, Vignesh / Cao, Hongbin / Zhang, Weiruo / Guan, Li / Chamoli, Manish / Holmes, Brittany / Kong, Christina / Hildebrand, Rachel / Koong, Amanda Jeanette / von Eyben, Rie / Plevritis, Sylvia / Li, Lingyin / Giaccia, Amato / Engleman, Edgar / Le, Quynh Thu

Cancer research

2023 Volume 83, Issue 19, Page(s) 3205–3219

Abstract: The immune system plays a crucial role in the regulation of metastasis. Tumor cells systemically change immune functions to facilitate metastatic progression. Through this study, we deciphered how tumoral galectin-1 (Gal1) expression shapes the systemic ... ...

Abstract	The immune system plays a crucial role in the regulation of metastasis. Tumor cells systemically change immune functions to facilitate metastatic progression. Through this study, we deciphered how tumoral galectin-1 (Gal1) expression shapes the systemic immune environment to promote metastasis in head and neck cancer (HNC). In multiple preclinical models of HNC and lung cancer in immunogenic mice, Gal1 fostered the establishment of a premetastatic niche through polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC), which altered the local microenvironment to support metastatic spread. RNA sequencing of MDSCs from premetastatic lungs in these models demonstrated the role of PMN-MDSCs in collagen and extracellular matrix remodeling in the premetastatic compartment. Gal1 promoted MDSC accumulation in the premetastatic niche through the NF-κB signaling axis, triggering enhanced CXCL2-mediated MDSC migration. Mechanistically, Gal1 sustained NF-κB activation in tumor cells by enhancing stimulator of interferon gene (STING) protein stability, leading to prolonged inflammation-driven MDSC expansion. These findings suggest an unexpected protumoral role of STING activation in metastatic progression and establish Gal1 as an endogenous-positive regulator of STING in advanced-stage cancers. Significance: Galectin-1 increases STING stability in cancer cells that activates NF-κB signaling and CXCL2 expression to promote MDSC trafficking, which stimulates the generation of a premetastatic niche and facilitates metastatic progression.
MeSH term(s)	Animals ; Mice ; Galectin 1/genetics ; Galectin 1/metabolism ; Lung Neoplasms/metabolism ; Myeloid-Derived Suppressor Cells/metabolism ; NF-kappa B/metabolism ; Signal Transduction ; Tumor Microenvironment/physiology
Chemical Substances	Galectin 1 ; NF-kappa B ; Sting1 protein, mouse
Language	English
Publishing date	2023-07-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-23-0046
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Article ; Online: Towards in vivo estimation of reaction kinetics using high-throughput metabolomics data: a maximum likelihood approach.

Zhang, Weiruo / Kolte, Ritesh / Dill, David L

BMC systems biology

2015 Volume 9, Page(s) 66

Abstract: Background: High-throughput assays such as mass spectrometry have opened up the possibility for large-scale in vivo measurements of the metabolome. This data could potentially be used to estimate kinetic parameters for many metabolic reactions. However, ...

Abstract	Background: High-throughput assays such as mass spectrometry have opened up the possibility for large-scale in vivo measurements of the metabolome. This data could potentially be used to estimate kinetic parameters for many metabolic reactions. However, high-throughput in vivo measurements have special properties that are not taken into account in existing methods for estimating kinetic parameters, including significant relative errors in measurements of metabolite concentrations and reaction rates, and reactions with multiple substrates and products, which are sometimes reversible. A new method is needed to estimate kinetic parameters taking into account these factors. Results: A new method, InVEst (In Vivo Estimation), is described for estimating reaction kinetic parameters, which addresses the specific challenges of in vivo data. InVEst uses maximum likelihood estimation based on a model where all measurements have relative errors. Simulations show that InVEst produces accurate estimates for a reversible enzymatic reaction with multiple reactants and products, that estimated parameters can be used to predict the effects of genetic variants, and that InVEst is more accurate than general least squares and graphic methods on data with relative errors. InVEst uses the bootstrap method to evaluate the accuracy of its estimates. Conclusions: InVEst addresses several challenges of in vivo data, which are not taken into account by existing methods. When data have relative errors, InVEst produces more accurate and robust estimates. InVEst also provides useful information about estimation accuracy using bootstrapping. It has potential applications of quantifying the effects of genetic variants, inference of the target of a mutation or drug treatment and improving flux estimation.
MeSH term(s)	Algorithms ; Computer Simulation ; Kinetics ; Likelihood Functions ; Metabolomics ; Models, Biological ; Systems Biology/methods
Language	English
Publishing date	2015-10-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1752-0509
ISSN (online)	1752-0509
DOI	10.1186/s12918-015-0214-7
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Article ; Online: Multiomics Analysis of Spatially Distinct Stromal Cells Reveals Tumor-Induced O-Glycosylation of the CDK4-pRB Axis in Fibroblasts at the Invasive Tumor Edge.

Bouchard, Gina / Garcia-Marques, Fernando Jose / Karacosta, Loukia Georgiou / Zhang, Weiruo / Bermudez, Abel / Riley, Nicholas McIlvain / Varma, Sushama / Mehl, Lindsey Catherine / Benson, Jalen Anthony / Shrager, Joseph B / Bertozzi, Carolyn Ruth / Pitteri, Sharon J / Giaccia, Amato J / Plevritis, Sylvia Katina

Cancer research

2022 Volume 82, Issue 4, Page(s) 648–664

Abstract: The invasive leading edge represents a potential gateway for tumor metastasis. The role of fibroblasts from the tumor edge in promoting cancer invasion and metastasis has not been comprehensively elucidated. We hypothesize that cross-talk between tumor ... ...

Abstract	The invasive leading edge represents a potential gateway for tumor metastasis. The role of fibroblasts from the tumor edge in promoting cancer invasion and metastasis has not been comprehensively elucidated. We hypothesize that cross-talk between tumor and stromal cells within the tumor microenvironment results in activation of key biological pathways depending on their position in the tumor (edge vs. core). Here we highlight phenotypic differences between tumor-adjacent-fibroblasts (TAF) from the invasive edge and tumor core fibroblasts from the tumor core, established from human lung adenocarcinomas. A multiomics approach that includes genomics, proteomics, and O-glycoproteomics was used to characterize cross-talk between TAFs and cancer cells. These analyses showed that O-glycosylation, an essential posttranslational modification resulting from sugar metabolism, alters key biological pathways including the cyclin-dependent kinase 4 (CDK4) and phosphorylated retinoblastoma protein axis in the stroma and indirectly modulates proinvasive features of cancer cells. In summary, the O-glycoproteome represents a new consideration for important biological processes involved in tumor-stroma cross-talk and a potential avenue to improve the anticancer efficacy of CDK4 inhibitors. Significance: A multiomics analysis of spatially distinct fibroblasts establishes the importance of the stromal O-glycoproteome in tumor-stroma interactions at the leading edge and provides potential strategies to improve cancer treatment. See related commentary by De Wever, p. 537.
MeSH term(s)	A549 Cells ; Cancer-Associated Fibroblasts/metabolism ; Cell Line, Tumor ; Cyclin-Dependent Kinase 4/genetics ; Cyclin-Dependent Kinase 4/metabolism ; Genomics/methods ; Glycoproteins/genetics ; Glycoproteins/metabolism ; Glycosylation ; Humans ; Neoplasm Invasiveness ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Phosphorylation ; Proteomics/methods ; Retinoblastoma Protein/genetics ; Retinoblastoma Protein/metabolism ; Signal Transduction/genetics ; Stromal Cells/metabolism ; Transcriptome/genetics
Chemical Substances	Glycoproteins ; Retinoblastoma Protein ; CDK4 protein, human (EC 2.7.11.22) ; Cyclin-Dependent Kinase 4 (EC 2.7.11.22)
Language	English
Publishing date	2022-07-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-21-1705
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Article ; Online: Identification of cell types in multiplexed in situ images by combining protein expression and spatial information using CELESTA.

Zhang, Weiruo / Li, Irene / Reticker-Flynn, Nathan E / Good, Zinaida / Chang, Serena / Samusik, Nikolay / Saumyaa, Saumyaa / Li, Yuanyuan / Zhou, Xin / Liang, Rachel / Kong, Christina S / Le, Quynh-Thu / Gentles, Andrew J / Sunwoo, John B / Nolan, Garry P / Engleman, Edgar G / Plevritis, Sylvia K

Nature methods

2022 Volume 19, Issue 6, Page(s) 759–769

Abstract: Advances in multiplexed in situ imaging are revealing important insights in spatial biology. However, cell type identification remains a major challenge in imaging analysis, with most existing methods involving substantial manual assessment and ... ...

Abstract	Advances in multiplexed in situ imaging are revealing important insights in spatial biology. However, cell type identification remains a major challenge in imaging analysis, with most existing methods involving substantial manual assessment and subjective decisions for thousands of cells. We developed an unsupervised machine learning algorithm, CELESTA, which identifies the cell type of each cell, individually, using the cell's marker expression profile and, when needed, its spatial information. We demonstrate the performance of CELESTA on multiplexed immunofluorescence images of colorectal cancer and head and neck squamous cell carcinoma (HNSCC). Using the cell types identified by CELESTA, we identify tissue architecture associated with lymph node metastasis in HNSCC, and validate our findings in an independent cohort. By coupling our spatial analysis with single-cell RNA-sequencing data on proximal sections of the same specimens, we identify cell-cell crosstalk associated with lymph node metastasis, demonstrating the power of CELESTA to facilitate identification of clinically relevant interactions.
MeSH term(s)	Cohort Studies ; Head and Neck Neoplasms ; Humans ; Lymphatic Metastasis ; Squamous Cell Carcinoma of Head and Neck
Language	English
Publishing date	2022-06-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2169522-2
ISSN	1548-7105 ; 1548-7091
ISSN (online)	1548-7105
ISSN	1548-7091
DOI	10.1038/s41592-022-01498-z
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Article ; Online: NFE2L2 Mutations Enhance Radioresistance in Head and Neck Cancer by Modulating Intratumoral Myeloid Cells.

Cancer research

2023 Volume 83, Issue 6, Page(s) 861–874

Abstract: Radiotherapy (RT) is one of the primary treatments of head and neck squamous cell carcinoma (HNSCC), which has a high-risk of locoregional failure (LRF). Presently, there is no reliable predictive biomarker of radioresistance in HNSCC. Here, we found ... ...

Abstract	Radiotherapy (RT) is one of the primary treatments of head and neck squamous cell carcinoma (HNSCC), which has a high-risk of locoregional failure (LRF). Presently, there is no reliable predictive biomarker of radioresistance in HNSCC. Here, we found that mutations in NFE2L2, which encodes Nrf2, are associated with a significantly higher rate of LRF in patients with oral cavity cancer treated with surgery and adjuvant (chemo)radiotherapy but not in those treated with surgery alone. Somatic mutation of NFE2L2 led to Nrf2 activation and radioresistance in HNSCC cells. Tumors harboring mutant Nrf2E79Q were substantially more radioresistant than tumors with wild-type Nrf2 in immunocompetent mice, whereas the difference was diminished in immunocompromised mice. Nrf2E79Q enhanced radioresistance through increased recruitment of intratumoral polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) and reduction of M1-polarized macrophages. Treatment with the glutaminase inhibitor CB-839 overcame the radioresistance induced by Nrf2E79Q or Nrf2E79K. RT increased expression of PMN-MDSC-attracting chemokines, including CXCL1, CXLC3, and CSF3, in Nrf2E79Q-expressing tumors via the TLR4, which could be reversed by CB-839. This study provides insights into the impact of NFE2L2 mutations on radioresistance and suggests that CB-839 can increase radiosensitivity by switching intratumoral myeloid cells to an antitumor phenotype, supporting clinical testing of CB-839 with RT in HNSCC with NFE2L2 mutations. Significance: NFE2L2 mutations are predictive biomarkers of radioresistance in head and neck cancer and confer sensitivity to glutaminase inhibitors to overcome radioresistance.
MeSH term(s)	Animals ; Mice ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/radiotherapy ; Carcinoma, Squamous Cell/pathology ; Glutaminase/metabolism ; Head and Neck Neoplasms/genetics ; Head and Neck Neoplasms/radiotherapy ; Head and Neck Neoplasms/metabolism ; Mutation ; Myeloid-Derived Suppressor Cells/metabolism ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Radiation Tolerance/genetics ; Squamous Cell Carcinoma of Head and Neck/genetics ; Squamous Cell Carcinoma of Head and Neck/radiotherapy ; Squamous Cell Carcinoma of Head and Neck/metabolism ; Humans
Chemical Substances	CB-839 ; Glutaminase (EC 3.5.1.2) ; NF-E2-Related Factor 2 ; Nfe2l2 protein, mouse ; NFE2L2 protein, human
Language	English
Publishing date	2023-01-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-22-1903
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Article ; Online: Organization of the human intestine at single-cell resolution.

Hickey, John W / Becker, Winston R / Nevins, Stephanie A / Horning, Aaron / Perez, Almudena Espin / Zhu, Chenchen / Zhu, Bokai / Wei, Bei / Chiu, Roxanne / Chen, Derek C / Cotter, Daniel L / Esplin, Edward D / Weimer, Annika K / Caraccio, Chiara / Venkataraaman, Vishal / Schürch, Christian M / Black, Sarah / Brbić, Maria / Cao, Kaidi /

Chen, Shuxiao / Zhang, Weiruo / Monte, Emma / Zhang, Nancy R / Ma, Zongming / Leskovec, Jure / Zhang, Zhengyan / Lin, Shin / Longacre, Teri / Plevritis, Sylvia K / Lin, Yiing / Nolan, Garry P / Greenleaf, William J / Snyder, Michael

Nature

2023 Volume 619, Issue 7970, Page(s) 572–584

Abstract: The intestine is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota and affects overall ... ...

Abstract	The intestine is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota and affects overall health
MeSH term(s)	Humans ; Cell Differentiation/genetics ; Chromatin/genetics ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Gene Expression Regulation ; Intestinal Mucosa/cytology ; Intestines/cytology ; Intestines/immunology ; Single-Cell Analysis ; Single-Cell Gene Expression Analysis
Chemical Substances	Chromatin
Language	English
Publishing date	2023-07-19
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-023-05915-x
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Article: Lymph node colonization induces tumor-immune tolerance to promote distant metastasis

Reticker-Flynn, Nathan E. / Zhang, Weiruo / Belk, Julia A. / Basto, Pamela A. / Escalante, Nichole K. / Pilarowski, Genay O.W. / Bejnood, Alborz / Martins, Maria M. / Kenkel, Justin A. / Linde, Ian L. / Bagchi, Sreya / Yuan, Robert / Chang, Serena / Spitzer, Matthew H. / Carmi, Yaron / Cheng, Jiahan / Tolentino, Lorna L. / Choi, Okmi / Wu, Nancy /

Kong, Christina S. / Gentles, Andrew J. / Sunwoo, John B. / Satpathy, Ansuman T. / Plevritis, Sylvia K. / Engleman, Edgar G.

Cell. 2022 May 26, v. 185, no. 11

2022

Abstract: For many solid malignancies, lymph node (LN) involvement represents a harbinger of distant metastatic disease and, therefore, an important prognostic factor. Beyond its utility as a biomarker, whether and how LN metastasis plays an active role in shaping ...

Abstract	For many solid malignancies, lymph node (LN) involvement represents a harbinger of distant metastatic disease and, therefore, an important prognostic factor. Beyond its utility as a biomarker, whether and how LN metastasis plays an active role in shaping distant metastasis remains an open question. Here, we develop a syngeneic melanoma mouse model of LN metastasis to investigate how tumors spread to LNs and whether LN colonization influences metastasis to distant tissues. We show that an epigenetically instilled tumor-intrinsic interferon response program confers enhanced LN metastatic potential by enabling the evasion of NK cells and promoting LN colonization. LN metastases resist T cell-mediated cytotoxicity, induce antigen-specific regulatory T cells, and generate tumor-specific immune tolerance that subsequently facilitates distant tumor colonization. These effects extend to human cancers and other murine cancer models, implicating a conserved systemic mechanism by which malignancies spread to distant organs.
Keywords	biomarkers ; cytotoxicity ; humans ; immunosuppression ; interferons ; lymph nodes ; melanoma ; metastasis ; mice
Language	English
Dates of publication	2022-0526
Size	p. 1924-1942.e23.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2022.04.019
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Lymph node colonization induces tumor-immune tolerance to promote distant metastasis.

Reticker-Flynn, Nathan E / Zhang, Weiruo / Belk, Julia A / Basto, Pamela A / Escalante, Nichole K / Pilarowski, Genay O W / Bejnood, Alborz / Martins, Maria M / Kenkel, Justin A / Linde, Ian L / Bagchi, Sreya / Yuan, Robert / Chang, Serena / Spitzer, Matthew H / Carmi, Yaron / Cheng, Jiahan / Tolentino, Lorna L / Choi, Okmi / Wu, Nancy /

Kong, Christina S / Gentles, Andrew J / Sunwoo, John B / Satpathy, Ansuman T / Plevritis, Sylvia K / Engleman, Edgar G

Cell

2022 Volume 185, Issue 11, Page(s) 1924–1942.e23

Abstract	For many solid malignancies, lymph node (LN) involvement represents a harbinger of distant metastatic disease and, therefore, an important prognostic factor. Beyond its utility as a biomarker, whether and how LN metastasis plays an active role in shaping distant metastasis remains an open question. Here, we develop a syngeneic melanoma mouse model of LN metastasis to investigate how tumors spread to LNs and whether LN colonization influences metastasis to distant tissues. We show that an epigenetically instilled tumor-intrinsic interferon response program confers enhanced LN metastatic potential by enabling the evasion of NK cells and promoting LN colonization. LN metastases resist T cell-mediated cytotoxicity, induce antigen-specific regulatory T cells, and generate tumor-specific immune tolerance that subsequently facilitates distant tumor colonization. These effects extend to human cancers and other murine cancer models, implicating a conserved systemic mechanism by which malignancies spread to distant organs.
MeSH term(s)	Animals ; Immune Tolerance ; Immunotherapy ; Lymph Nodes ; Lymphatic Metastasis/pathology ; Melanoma/pathology ; Mice
Language	English
Publishing date	2022-05-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2022.04.019
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Article ; Online: GFPT2

Zhang, Weiruo / Bouchard, Gina / Yu, Alice / Shafiq, Majid / Jamali, Mehran / Shrager, Joseph B / Ayers, Kelsey / Bakr, Shaimaa / Gentles, Andrew J / Diehn, Maximilian / Quon, Andrew / West, Robert B / Nair, Viswam / van de Rijn, Matt / Napel, Sandy / Plevritis, Sylvia K

Cancer research

2018 Volume 78, Issue 13, Page(s) 3445–3457

Abstract: Metabolic reprogramming of the tumor microenvironment is recognized as a cancer hallmark. To identify new molecular processes associated with tumor metabolism, we analyzed the transcriptome of bulk and flow-sorted human primary non-small cell lung cancer ...

Abstract	Metabolic reprogramming of the tumor microenvironment is recognized as a cancer hallmark. To identify new molecular processes associated with tumor metabolism, we analyzed the transcriptome of bulk and flow-sorted human primary non-small cell lung cancer (NSCLC) together with
MeSH term(s)	Adenocarcinoma of Lung/diagnostic imaging ; Adenocarcinoma of Lung/mortality ; Adenocarcinoma of Lung/pathology ; Aged ; Aged, 80 and over ; Cancer-Associated Fibroblasts/metabolism ; Carcinoma, Non-Small-Cell Lung/diagnostic imaging ; Carcinoma, Non-Small-Cell Lung/mortality ; Carcinoma, Non-Small-Cell Lung/pathology ; Cell Line, Tumor ; Female ; Fluorodeoxyglucose F18/administration & dosage ; Follow-Up Studies ; Gene Expression Profiling ; Glucose Transporter Type 1/metabolism ; Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)/metabolism ; Glycolysis ; Glycosylation ; Hexosamines/biosynthesis ; Humans ; Lung Neoplasms/diagnostic imaging ; Lung Neoplasms/mortality ; Lung Neoplasms/pathology ; Male ; Middle Aged ; Neoplasm Invasiveness/diagnostic imaging ; Neoplasm Invasiveness/pathology ; Positron-Emission Tomography ; Prognosis ; Survival Analysis ; Tumor Microenvironment
Chemical Substances	Glucose Transporter Type 1 ; Hexosamines ; SLC2A1 protein, human ; Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; GFPT2 protein, human (EC 2.6.1.16) ; Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) (EC 2.6.1.16)
Language	English
Publishing date	2018-05-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-17-2928
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