Pennel, Kathryn and Kurniawan, Ahmad and Al-Badran, Sara Samir Foad and Schubert Santana, Leonor and Quinn, Jean and Nixon, Colin and Hatthakarnkul, Phimmada and Maka, Noori and Roxburgh, Campbell and McMillan, Donald and Edwards, Joanne (2024) IL6 and IL6R as prognostic biomarkers in colorectal cancer. Biomolecules, 14 (12): 1629. ISSN 2218-273X

Abstract

Colorectal cancer is the third most diagnosed malignancy worldwide and survival outcomes remain poor. Research is focused on the identification of novel prognostic and predictive biomarkers to improve clinical practice. There is robust evidence in the literature that inflammatory cytokine interleukin-6 (IL6) is elevated systemically in CRC patients and that this phenomenon is a predictor of poor survival outcome. However, evidence is more limited for the role of IL6 and its cognate receptor, IL6R, within the tumour epithelium and microenvironment. This study aimed to investigate IL6 and IL6R expression in a large cohort of retrospectively collected patient tumour specimens and determine association with clinical outcomes and characteristics. High expression of IL6R in the tumour epithelium was associated with reduced cancer-specific survival in patients with right-sided colon cancer. In these patients, high IL6R expression was also associated with an increased systemic neutrophil-to-lymphocyte ratio. A high number of copies of IL6 mRNA within the tumour-associated stroma, but not epithelium, was associated with reduced cancer-specific survival. The results from this study have validated IL6R as a marker of poor prognosis in a subgroup of CRC patients and identified the spatially resolved prognostic nature of intra-tumoural IL6 expression. This study has also highlighted the need for investigation of IL6/IL6R-targeted therapies as novel treatment strategies for patients with colon cancer.

People
Pennel, Kathryn A.F.
Author

Dolan, Ross D. and Pennel, Kathryn and Thompson, Joshua and McKenzie, Molly and Alexander, Peter and Richards, Colin and Black, Douglas and Abbass, Tanvir and Maka, Noori and McGovern, Josh and Roseweir, Antonia and McSorley, Stephen T. and Horgan, Paul G. and Roxburgh, Campbell and McMillan, Donald C. and Edwards, Joanne (2025) The relationship between tumour necrosis, systemic inflammation, body composition and survival in patients with colon cancer. BJC Reports, 3 (1): 7. ISSN 2731-9377

Pennel, Kathryn and Kurniawan, Ahmad and Al-Badran, Sara Samir Foad and Schubert Santana, Leonor and Quinn, Jean and Nixon, Colin and Hatthakarnkul, Phimmada and Maka, Noori and Roxburgh, Campbell and McMillan, Donald and Edwards, Joanne (2024) IL6 and IL6R as prognostic biomarkers in colorectal cancer. Biomolecules, 14 (12): 1629. ISSN 2218-273X

Galbraith, Norman J. and Quinn, Jean A. and Al-Badran, Sara Sf and Pennel, Kathryn A.F. and Hillson, Lily V.S. and Hatthakarnkul, Phimmada and McKenzie, Molly and Maka, Noori and Loi, Lynette and Frixou, Mikaela and Steele, Colin W. and Roxburgh, Campbell S. and Horgan, Paul G. and McMillan, Donald C. and Edwards, Joanne (2024) TAK1 expression is associated with increased PD-L1 and decreased cancer-specific survival in microsatellite-stable colorectal cancer. Translational Oncology, 48: 102064. ISSN 1944-7124

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Kurniawan, Ahmad
Author

Pennel, Kathryn and Kurniawan, Ahmad and Al-Badran, Sara Samir Foad and Schubert Santana, Leonor and Quinn, Jean and Nixon, Colin and Hatthakarnkul, Phimmada and Maka, Noori and Roxburgh, Campbell and McMillan, Donald and Edwards, Joanne (2024) IL6 and IL6R as prognostic biomarkers in colorectal cancer. Biomolecules, 14 (12): 1629. ISSN 2218-273X

Pennel, Kathryn A.F. and Hatthakarnkul, Phimmada and Wood, Colin S. and Lian, Guang-Yu and Al-Badran, Sara and Quinn, Jean A. and Legrini, Assya and Inthagard, Jitwadee and Alexander, Peter G. and van Wyk, Hester and Kurniawan, Ahmad and Hashmi, Umar and Gillespie, Michael A. and Mills, Megan and Ammar, Aula and Hay, Jennifer and Andersen, Ditte and Nixon, Colin and Rebus, Selma and Chang, David K. and Kelly, Caroline and Harkin, Andrea and Graham, Janet and Church, David and Tomlinson, Ian and Saunders, Mark and Iveson, Tim and Lannagan, Tamsin R. M. and Jackstadt, Rene and Maka, Noori and Horgan, Paul G. and Roxburgh, Campbell S. D. and Sansom, Owen J. and McMillan, Donald C. and Steele, Colin W. and Jamieson, Nigel B. and Park, James H. and Roseweir, Antonia K. and Edwards, Joanne (2024) JAK/STAT3 represents a therapeutic target for colorectal cancer patients with stromal-rich tumors. Journal of Experimental and Clinical Cancer Research, 43: 64. ISSN 1756-9966

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Al-Badran, Sara S.F.
Author

Pennel, Kathryn and Kurniawan, Ahmad and Al-Badran, Sara Samir Foad and Schubert Santana, Leonor and Quinn, Jean and Nixon, Colin and Hatthakarnkul, Phimmada and Maka, Noori and Roxburgh, Campbell and McMillan, Donald and Edwards, Joanne (2024) IL6 and IL6R as prognostic biomarkers in colorectal cancer. Biomolecules, 14 (12): 1629. ISSN 2218-273X

Shamis, Suad A.K. and Quinn, Jean and Al-Badran, Sara and McKenzie, Molly and Hatthakarnkul, Phimmada and Lynch, Gerard and Lian, Guang-Yu and Numprasit, Warapan and Romics Jr, Laszlo and Andersen, Ditte and Mallon, Elizabeth and McMillan, Donald C. and Edwards, Joanne (2024) Elucidation of dysregulated pathways associated with hypoxia in oestrogen receptor-negative breast cancer. Cancer Medicine, 13 (23): e70274. ISSN 2045-7634

Galbraith, Norman J. and Quinn, Jean A. and Al-Badran, Sara Sf and Pennel, Kathryn A.F. and Hillson, Lily V.S. and Hatthakarnkul, Phimmada and McKenzie, Molly and Maka, Noori and Loi, Lynette and Frixou, Mikaela and Steele, Colin W. and Roxburgh, Campbell S. and Horgan, Paul G. and McMillan, Donald C. and Edwards, Joanne (2024) TAK1 expression is associated with increased PD-L1 and decreased cancer-specific survival in microsatellite-stable colorectal cancer. Translational Oncology, 48: 102064. ISSN 1944-7124

See full publications list
Schubert Santana, Leonor
Author

Pennel, Kathryn and Kurniawan, Ahmad and Al-Badran, Sara Samir Foad and Schubert Santana, Leonor and Quinn, Jean and Nixon, Colin and Hatthakarnkul, Phimmada and Maka, Noori and Roxburgh, Campbell and McMillan, Donald and Edwards, Joanne (2024) IL6 and IL6R as prognostic biomarkers in colorectal cancer. Biomolecules, 14 (12): 1629. ISSN 2218-273X

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Quinn, Jean A.
Author

Pennel, Kathryn and Kurniawan, Ahmad and Al-Badran, Sara Samir Foad and Schubert Santana, Leonor and Quinn, Jean and Nixon, Colin and Hatthakarnkul, Phimmada and Maka, Noori and Roxburgh, Campbell and McMillan, Donald and Edwards, Joanne (2024) IL6 and IL6R as prognostic biomarkers in colorectal cancer. Biomolecules, 14 (12): 1629. ISSN 2218-273X

Shamis, Suad A.K. and Quinn, Jean and Al-Badran, Sara and McKenzie, Molly and Hatthakarnkul, Phimmada and Lynch, Gerard and Lian, Guang-Yu and Numprasit, Warapan and Romics Jr, Laszlo and Andersen, Ditte and Mallon, Elizabeth and McMillan, Donald C. and Edwards, Joanne (2024) Elucidation of dysregulated pathways associated with hypoxia in oestrogen receptor-negative breast cancer. Cancer Medicine, 13 (23): e70274. ISSN 2045-7634

Galbraith, Norman J. and Quinn, Jean A. and Al-Badran, Sara Sf and Pennel, Kathryn A.F. and Hillson, Lily V.S. and Hatthakarnkul, Phimmada and McKenzie, Molly and Maka, Noori and Loi, Lynette and Frixou, Mikaela and Steele, Colin W. and Roxburgh, Campbell S. and Horgan, Paul G. and McMillan, Donald C. and Edwards, Joanne (2024) TAK1 expression is associated with increased PD-L1 and decreased cancer-specific survival in microsatellite-stable colorectal cancer. Translational Oncology, 48: 102064. ISSN 1944-7124

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Nixon, Colin
Author

Elbassioni, Ali Ali Mohamed and Raheem, Anmar A. and Song, Jian and Johnston, Alexander S. and Trivett, Cara and Lin, Hong and Zhang, Haobo and Bradley, Ashley and Higgins, Erin and Mooney, Leanne and Koay, Yen Chin and O'Toole, Dylan and Herzyk, Pawel and Nixon, Colin and Blyth, Karen and O'Sullivan, John F. and Lang, Ninian N. and Berry, Colin and Braun, Thomas and Schiattarella, Gabriele G. and Giacca, Mauro and McBride, Martin W. and Nicklin, Stuart A. and Cameron, Ewan R. and Loughrey, Christopher M. and MacDonald, Eilidh A. (2025) Targeting Runx1 protects against heart failure with preserved ejection fraction. bioRxiv.

Pennel, Kathryn and Kurniawan, Ahmad and Al-Badran, Sara Samir Foad and Schubert Santana, Leonor and Quinn, Jean and Nixon, Colin and Hatthakarnkul, Phimmada and Maka, Noori and Roxburgh, Campbell and McMillan, Donald and Edwards, Joanne (2024) IL6 and IL6R as prognostic biomarkers in colorectal cancer. Biomolecules, 14 (12): 1629. ISSN 2218-273X

Churchhouse, Antonia M.D. and Billard, Caroline V. and Suzuki, Toshiyasu and Pohl, Sebastian O.G. and Donnelly, Kevin and Nixon, Colin and Arends, Mark J. and Din, Shahida and Kirkwood, Kathryn and Marques Junior, Jair and Von Kriegsheim, Alexander and Coffelt, Seth B. and Myant, Kevin B. (2024) Loss of DOCK2 potentiates Inflammatory Bowel Disease-associated colorectal cancer via immune dysfunction and IFNγ induction of IDO1 expression. Oncogene, 43 (42). pp. 3094-3107. ISSN 0950-9232

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Hatthakarnkul, Phimmada
Author

Pennel, Kathryn and Kurniawan, Ahmad and Al-Badran, Sara Samir Foad and Schubert Santana, Leonor and Quinn, Jean and Nixon, Colin and Hatthakarnkul, Phimmada and Maka, Noori and Roxburgh, Campbell and McMillan, Donald and Edwards, Joanne (2024) IL6 and IL6R as prognostic biomarkers in colorectal cancer. Biomolecules, 14 (12): 1629. ISSN 2218-273X

Shamis, Suad A.K. and Quinn, Jean and Al-Badran, Sara and McKenzie, Molly and Hatthakarnkul, Phimmada and Lynch, Gerard and Lian, Guang-Yu and Numprasit, Warapan and Romics Jr, Laszlo and Andersen, Ditte and Mallon, Elizabeth and McMillan, Donald C. and Edwards, Joanne (2024) Elucidation of dysregulated pathways associated with hypoxia in oestrogen receptor-negative breast cancer. Cancer Medicine, 13 (23): e70274. ISSN 2045-7634

Galbraith, Norman J. and Quinn, Jean A. and Al-Badran, Sara Sf and Pennel, Kathryn A.F. and Hillson, Lily V.S. and Hatthakarnkul, Phimmada and McKenzie, Molly and Maka, Noori and Loi, Lynette and Frixou, Mikaela and Steele, Colin W. and Roxburgh, Campbell S. and Horgan, Paul G. and McMillan, Donald C. and Edwards, Joanne (2024) TAK1 expression is associated with increased PD-L1 and decreased cancer-specific survival in microsatellite-stable colorectal cancer. Translational Oncology, 48: 102064. ISSN 1944-7124

See full publications list
Maka, Noori
Author

Dolan, Ross D. and Pennel, Kathryn and Thompson, Joshua and McKenzie, Molly and Alexander, Peter and Richards, Colin and Black, Douglas and Abbass, Tanvir and Maka, Noori and McGovern, Josh and Roseweir, Antonia and McSorley, Stephen T. and Horgan, Paul G. and Roxburgh, Campbell and McMillan, Donald C. and Edwards, Joanne (2025) The relationship between tumour necrosis, systemic inflammation, body composition and survival in patients with colon cancer. BJC Reports, 3 (1): 7. ISSN 2731-9377

Pennel, Kathryn and Kurniawan, Ahmad and Al-Badran, Sara Samir Foad and Schubert Santana, Leonor and Quinn, Jean and Nixon, Colin and Hatthakarnkul, Phimmada and Maka, Noori and Roxburgh, Campbell and McMillan, Donald and Edwards, Joanne (2024) IL6 and IL6R as prognostic biomarkers in colorectal cancer. Biomolecules, 14 (12): 1629. ISSN 2218-273X

Galbraith, Norman J. and Quinn, Jean A. and Al-Badran, Sara Sf and Pennel, Kathryn A.F. and Hillson, Lily V.S. and Hatthakarnkul, Phimmada and McKenzie, Molly and Maka, Noori and Loi, Lynette and Frixou, Mikaela and Steele, Colin W. and Roxburgh, Campbell S. and Horgan, Paul G. and McMillan, Donald C. and Edwards, Joanne (2024) TAK1 expression is associated with increased PD-L1 and decreased cancer-specific survival in microsatellite-stable colorectal cancer. Translational Oncology, 48: 102064. ISSN 1944-7124

See full publications list
Roxburgh, Campbell S. D.
Author

Bradley, Nicholas A. and Walter, Amy and Sankey, Chiara and Wilson, Alasdair and Siddiqui, Tamim and Roxburgh, Campbell D. and McMillan, Donald C. and Guthrie, Graeme J.K. (2025) Longitudinal association between statins and changes in CT derived body composition in patients with abdominal aortic aneurysm. Journal of Cachexia, Sarcopenia and Muscle, 16 (2). ISSN 2190-5991

Thompson, Joshua J. and MacLeod, Nicholas and Will, Sarah and O'Rourke, Fraser and McGovern, Josh and Roxburgh, Campbell and Edwards, Joanne and Dolan, Ross D. and McMillan, Donald C. (2025) The prognostic value of a laboratory cachexia score (LCAS) defined by LDH, CRP and albumin in patients with advanced lung cancer. BMC Cancer, 25: 543. ISSN 1471-2407

Dolan, Ross D. and Pennel, Kathryn and Thompson, Joshua and McKenzie, Molly and Alexander, Peter and Richards, Colin and Black, Douglas and Abbass, Tanvir and Maka, Noori and McGovern, Josh and Roseweir, Antonia and McSorley, Stephen T. and Horgan, Paul G. and Roxburgh, Campbell and McMillan, Donald C. and Edwards, Joanne (2025) The relationship between tumour necrosis, systemic inflammation, body composition and survival in patients with colon cancer. BJC Reports, 3 (1): 7. ISSN 2731-9377

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McMillan, D.C.
Author

Bradley, Nicholas A. and Walter, Amy and Sankey, Chiara and Wilson, Alasdair and Siddiqui, Tamim and Roxburgh, Campbell D. and McMillan, Donald C. and Guthrie, Graeme J.K. (2025) Longitudinal association between statins and changes in CT derived body composition in patients with abdominal aortic aneurysm. Journal of Cachexia, Sarcopenia and Muscle, 16 (2). ISSN 2190-5991

Thompson, Joshua J. and MacLeod, Nicholas and Will, Sarah and O'Rourke, Fraser and McGovern, Josh and Roxburgh, Campbell and Edwards, Joanne and Dolan, Ross D. and McMillan, Donald C. (2025) The prognostic value of a laboratory cachexia score (LCAS) defined by LDH, CRP and albumin in patients with advanced lung cancer. BMC Cancer, 25: 543. ISSN 1471-2407

Dolan, Ross D. and Pennel, Kathryn and Thompson, Joshua and McKenzie, Molly and Alexander, Peter and Richards, Colin and Black, Douglas and Abbass, Tanvir and Maka, Noori and McGovern, Josh and Roseweir, Antonia and McSorley, Stephen T. and Horgan, Paul G. and Roxburgh, Campbell and McMillan, Donald C. and Edwards, Joanne (2025) The relationship between tumour necrosis, systemic inflammation, body composition and survival in patients with colon cancer. BJC Reports, 3 (1): 7. ISSN 2731-9377

See full publications list
Edwards, J.
Author

Thompson, Joshua J. and MacLeod, Nicholas and Will, Sarah and O'Rourke, Fraser and McGovern, Josh and Roxburgh, Campbell and Edwards, Joanne and Dolan, Ross D. and McMillan, Donald C. (2025) The prognostic value of a laboratory cachexia score (LCAS) defined by LDH, CRP and albumin in patients with advanced lung cancer. BMC Cancer, 25: 543. ISSN 1471-2407

Dolan, Ross D. and Pennel, Kathryn and Thompson, Joshua and McKenzie, Molly and Alexander, Peter and Richards, Colin and Black, Douglas and Abbass, Tanvir and Maka, Noori and McGovern, Josh and Roseweir, Antonia and McSorley, Stephen T. and Horgan, Paul G. and Roxburgh, Campbell and McMillan, Donald C. and Edwards, Joanne (2025) The relationship between tumour necrosis, systemic inflammation, body composition and survival in patients with colon cancer. BJC Reports, 3 (1): 7. ISSN 2731-9377

Pennel, Kathryn and Kurniawan, Ahmad and Al-Badran, Sara Samir Foad and Schubert Santana, Leonor and Quinn, Jean and Nixon, Colin and Hatthakarnkul, Phimmada and Maka, Noori and Roxburgh, Campbell and McMillan, Donald and Edwards, Joanne (2024) IL6 and IL6R as prognostic biomarkers in colorectal cancer. Biomolecules, 14 (12): 1629. ISSN 2218-273X

See full publications list
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