Abstract
| Original language | English |
|---|---|
| Article number | 154518 |
| Number of pages | 7 |
| Journal | Pathology Research and Practice |
| Volume | 247 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Jul 2023 |
Keywords
- Colorectal cancer
- Warburg effect
- Tumour infiltrating lymphocytes
- Tumour stromal content
- LACTIC-ACID
- INFILTRATION
- METABOLISM
- EXPRESSION
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- 10.1016/j.prp.2023.154518Licence: CC BY
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In: Pathology Research and Practice, Vol. 247, No. 1, 154518, 01.07.2023.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Relationship between the Warburg effect in tumour cells and the tumour microenvironment in colorectal cancer patients
T2 - Results from a large multicentre study
AU - Steeghs, Jorn P.J.M.
AU - Offermans, Kelly
AU - Jenniskens, Josien C.A.
AU - Samarska, Iryna
AU - Fazzi, Gregorio E.
AU - van den Brandt, Piet A.
AU - Grabsch, Heike I.
N1 - Funding Information: The Rainbow-TMA consortium was financially supported by BBMRI-NL , a Research Infrastructure financed by the Dutch government (NWO 184.021.007 , to P. A. van den Brandt), and Maastricht University Medical Center+, University Medical Center Utrecht, and Radboud University Medical Center, the Netherlands. The authors would like to thank all investigators from the Rainbow-TMA consortium project group (P. A. van den Brandt, A. zur Hausen, H. Grabsch, M. van Engeland, L. J. Schouten, J. Beckervordersandforth [Maastricht University Medical Center, Maastricht, the Netherlands]; P. H. M. Peeters, P. J. van Diest, H. B. Bueno de Mesquita [University Medical Center Utrecht, Utrecht, the Netherlands]; J. van Krieken, I. Nagtegaal, B. Siebers, B. Kiemeney [Radboud University Medical Center, Nijmegen, the Netherlands]; F. J. van Kemenade, C. Steegers, D. Boomsma, G. A. Meijer (VU University Medical Center, Amsterdam, the Netherlands]; F. J. van Kemenade, B. Stricker [Erasmus University Medical Center, Rotterdam, the Netherlands]; L. Overbeek, A. Gijsbers (PALGA, the Nationwide Histopathology and Cytopathology Data Network and Archive, Houten, the Netherlands]) and collaborating pathologists (Among others: A. de Bruïne [VieCuri Medical Center, Venlo]; J. C. Beckervordersandforth [Maastricht University Medical Center, Maastricht]; J. van Krieken, I. Nagtegaal [Radboud University Medical Center, Nijmegen]; W. Timens [University Medical Center Groningen, Groningen]; F. J. van Kemenade [Erasmus University Medical Center, Rotterdam]; M. C. H. Hogenes [Laboratory for Pathology OostNederland, Hengelo]; P. J. van Diest [University Medical Center Utrecht, Utrecht]; R. E. Kibbelaar [Pathology Friesland, Leeuwarden]; A. F. Hamel [Stichting Samenwerkende Ziekenhuizen Oost-Groningen, Winschoten]; A. T. M. G. Tiebosch [Martini Hospital, Groningen]; C. Meijers [Reinier de Graaf Gasthuis/S. S. D. Z., Delft]; R. Natté [Haga Hospital Leyenburg, The Hague]; G. A. Meijer [VU University Medical Center, Amsterdam]; J. J. T. H. Roelofs [Academic Medical Center, Amsterdam]; R. F. Hoedemaeker [Pathology Laboratory Pathan, Rotterdam]; S. Sastrowijoto [Orbis Medical Center, Sittard]; M. Nap [Atrium Medical Center, Heerlen]; H. T. Shirango [Deventer Hospital, Deventer]; H. Doornewaard [Gelre Hospital, Apeldoorn]; J. E. Boers [Isala Hospital, Zwolle]; J. C. van der Linden [Jeroen Bosch Hospital, Den Bosch]; G. Burger [Symbiant Pathology Center, Alkmaar]; R. W. Rouse [Meander Medical Center, Amersfoort]; P. C. de Bruin [St. Antonius Hospital, Nieuwegein]; P. Drillenburg [Onze Lieve Vrouwe Gasthuis, Amsterdam]; C. van Krimpen [Kennemer Gasthuis, Haarlem]; J. F. Graadt van Roggen [Diaconessenhuis, Leiden]; S. A. J. Loyson [Bronovo Hospital, The Hague]; J. D. Rupa [Laurentius Hospital, Roermond]; H. Kliffen [Maasstad Hospital, Rotterdam]; H. M. Hazelbag [Medical Center Haaglanden, The Hague]; K. Schelfout [Stichting Pathologisch en Cytologisch Laboratorium West-Brabant, Bergen op Zoom]; J. Stavast [Laboratorium Klinische Pathologie Centraal Brabant, Tilburg]; I. van Lijnschoten [PAMM laboratory for Pathology and Medical Microbiology, Eindhoven]; K. Duthoi [Amphia Hospital, Breda]). This project was funded by The Dutch Cancer Society ( KWF 11044 to Piet A. van den Brandt). Funding Information: The authors would like to thank the participants of the Netherlands Cohort Study (NLCS), the Netherlands Cancer Registry, and the Dutch Pathology Registry. They are grateful to Ron Alofs and Harry van Montfort for data management and programming assistance; and to Jaleesa van der Meer, Edith van den Boezem, and Peter Moerkerk for TMA construction; and Jakob Kather (University Hospital Aachen, Germany) for scanning of TMA slides. H.I.G. is supported in part by the National Institute for Health and Care Research (NIHR) Leeds Biomedical Research Center. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The Rainbow-TMA consortium was financially supported by BBMRI-NL, a Research Infrastructure financed by the Dutch government (NWO 184.021.007, to P. A. van den Brandt), and Maastricht University Medical Center+, University Medical Center Utrecht, and Radboud University Medical Center, the Netherlands. The authors would like to thank all investigators from the Rainbow-TMA consortium project group (P. A. van den Brandt, A. zur Hausen, H. Grabsch, M. van Engeland, L. J. Schouten, J. Beckervordersandforth [Maastricht University Medical Center, Maastricht, the Netherlands]; P. H. M. Peeters, P. J. van Diest, H. B. Bueno de Mesquita [University Medical Center Utrecht, Utrecht, the Netherlands]; J. van Krieken, I. Nagtegaal, B. Siebers, B. Kiemeney [Radboud University Medical Center, Nijmegen, the Netherlands]; F. J. van Kemenade, C. Steegers, D. Boomsma, G. A. Meijer (VU University Medical Center, Amsterdam, the Netherlands]; F. J. van Kemenade, B. Stricker [Erasmus University Medical Center, Rotterdam, the Netherlands]; L. Overbeek, A. Gijsbers (PALGA, the Nationwide Histopathology and Cytopathology Data Network and Archive, Houten, the Netherlands]) and collaborating pathologists (Among others: A. de Bruïne [VieCuri Medical Center, Venlo]; J. C. Beckervordersandforth [Maastricht University Medical Center, Maastricht]; J. van Krieken, I. Nagtegaal [Radboud University Medical Center, Nijmegen]; W. Timens [University Medical Center Groningen, Groningen]; F. J. van Kemenade [Erasmus University Medical Center, Rotterdam]; M. C. H. Hogenes [Laboratory for Pathology OostNederland, Hengelo]; P. J. van Diest [University Medical Center Utrecht, Utrecht]; R. E. Kibbelaar [Pathology Friesland, Leeuwarden]; A. F. Hamel [Stichting Samenwerkende Ziekenhuizen Oost-Groningen, Winschoten]; A. T. M. G. Tiebosch [Martini Hospital, Groningen]; C. Meijers [Reinier de Graaf Gasthuis/S. S. D. Z. Delft]; R. Natté [Haga Hospital Leyenburg, The Hague]; G. A. Meijer [VU University Medical Center, Amsterdam]; J. J. T. H. Roelofs [Academic Medical Center, Amsterdam]; R. F. Hoedemaeker [Pathology Laboratory Pathan, Rotterdam]; S. Sastrowijoto [Orbis Medical Center, Sittard]; M. Nap [Atrium Medical Center, Heerlen]; H. T. Shirango [Deventer Hospital, Deventer]; H. Doornewaard [Gelre Hospital, Apeldoorn]; J. E. Boers [Isala Hospital, Zwolle]; J. C. van der Linden [Jeroen Bosch Hospital, Den Bosch]; G. Burger [Symbiant Pathology Center, Alkmaar]; R. W. Rouse [Meander Medical Center, Amersfoort]; P. C. de Bruin [St. Antonius Hospital, Nieuwegein]; P. Drillenburg [Onze Lieve Vrouwe Gasthuis, Amsterdam]; C. van Krimpen [Kennemer Gasthuis, Haarlem]; J. F. Graadt van Roggen [Diaconessenhuis, Leiden]; S. A. J. Loyson [Bronovo Hospital, The Hague]; J. D. Rupa [Laurentius Hospital, Roermond]; H. Kliffen [Maasstad Hospital, Rotterdam]; H. M. Hazelbag [Medical Center Haaglanden, The Hague]; K. Schelfout [Stichting Pathologisch en Cytologisch Laboratorium West-Brabant, Bergen op Zoom]; J. Stavast [Laboratorium Klinische Pathologie Centraal Brabant, Tilburg]; I. van Lijnschoten [PAMM laboratory for Pathology and Medical Microbiology, Eindhoven]; K. Duthoi [Amphia Hospital, Breda]). This project was funded by The Dutch Cancer Society (KWF 11044 to Piet A. van den Brandt). Funding Information: The authors would like to thank the participants of the Netherlands Cohort Study (NLCS), the Netherlands Cancer Registry, and the Dutch Pathology Registry. They are grateful to Ron Alofs and Harry van Montfort for data management and programming assistance; and to Jaleesa van der Meer, Edith van den Boezem, and Peter Moerkerk for TMA construction; and Jakob Kather (University Hospital Aachen, Germany) for scanning of TMA slides. H.I.G. is supported in part by the National Institute for Health and Care Research (NIHR) Leeds Biomedical Research Center. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Publisher Copyright: © 2023 The Authors
PY - 2023/7/1
Y1 - 2023/7/1
N2 - Colorectal cancer (CRC) remains one of the most prevalent and deadly cancers worldwide. The tumour-node-metastasis stage (TNM) is currently the most clinically important tool to predict prognosis for CRC patients. However, patients with the same TNM stage can have different prognoses. The metabolic status of tumour cells (Warburg-subtype) has been proposed as potential prognostic factor in CRC. However, potential biological mechanisms underlying the relationship between Warburg-subtype and prognosis have not been investigated in detail. One potential mechanism could be that the metabolic status of tumour cells affects the tumour microenvironment (TME). Our objective was to investigate the relationship between Warburg-subtypes and the TME. Haematoxylin/Eosin stained tumour tissue microarray cores from 2171 CRC patients from the Netherlands Cohort Study were semi quantitatively assessed for tumour infiltrating lymphocytes (TILs) and relative tumour stroma content. 5745 cores were assessed by putting each core in one of four categories for both TILs and stroma. The relationship between Warburg-subtype, TILs, and tumour stroma content was investigated. The frequency of CRC in the different TIL categories was (n, %): very low (2538, 44.2), low (2463, 42.9), high (722, 12.6), and very high (22, 0.4). The frequency of CRC in the different tumour stroma content categories was: = 25% (2755, 47.9), > 25% = 50% (1553, 27) > 50% = 75% (905, 15.8), and > 75% (532, 9.3). There was neither an association between Warburg-subtype and tumour stroma content (p = 0.229) nor between Warburg-subtype and TILs (p = 0.429). This is the first study to investigate the relationship between Warburg-subtypes and the TME in a large population-based series of CRC patients. Our data suggest that the prognostic value of Warburg-subtypes cannot be directly attributed to differences in TILs or tumour stroma content. Our results require confirmation in an independent series.
AB - Colorectal cancer (CRC) remains one of the most prevalent and deadly cancers worldwide. The tumour-node-metastasis stage (TNM) is currently the most clinically important tool to predict prognosis for CRC patients. However, patients with the same TNM stage can have different prognoses. The metabolic status of tumour cells (Warburg-subtype) has been proposed as potential prognostic factor in CRC. However, potential biological mechanisms underlying the relationship between Warburg-subtype and prognosis have not been investigated in detail. One potential mechanism could be that the metabolic status of tumour cells affects the tumour microenvironment (TME). Our objective was to investigate the relationship between Warburg-subtypes and the TME. Haematoxylin/Eosin stained tumour tissue microarray cores from 2171 CRC patients from the Netherlands Cohort Study were semi quantitatively assessed for tumour infiltrating lymphocytes (TILs) and relative tumour stroma content. 5745 cores were assessed by putting each core in one of four categories for both TILs and stroma. The relationship between Warburg-subtype, TILs, and tumour stroma content was investigated. The frequency of CRC in the different TIL categories was (n, %): very low (2538, 44.2), low (2463, 42.9), high (722, 12.6), and very high (22, 0.4). The frequency of CRC in the different tumour stroma content categories was: = 25% (2755, 47.9), > 25% = 50% (1553, 27) > 50% = 75% (905, 15.8), and > 75% (532, 9.3). There was neither an association between Warburg-subtype and tumour stroma content (p = 0.229) nor between Warburg-subtype and TILs (p = 0.429). This is the first study to investigate the relationship between Warburg-subtypes and the TME in a large population-based series of CRC patients. Our data suggest that the prognostic value of Warburg-subtypes cannot be directly attributed to differences in TILs or tumour stroma content. Our results require confirmation in an independent series.
KW - Colorectal cancer
KW - Warburg effect
KW - Tumour infiltrating lymphocytes
KW - Tumour stromal content
KW - LACTIC-ACID
KW - INFILTRATION
KW - METABOLISM
KW - EXPRESSION
U2 - 10.1016/j.prp.2023.154518
DO - 10.1016/j.prp.2023.154518
M3 - Article
C2 - 37209573
SN - 0344-0338
VL - 247
JO - Pathology Research and Practice
JF - Pathology Research and Practice
IS - 1
M1 - 154518
ER -