Perturbations in the neuroactive ligand-receptor interaction and renin angiotensin system pathways are associated with cancer-related cognitive impairment

Raymond J. Chan; Adam Walker; Janette Vardy; Alexandre Chan; Kate Oppegaard; Yvette P. Conley; Steven M. Paul; Kord M. Kober; Carolyn Harris; Joosun Shin; Lisa Morse; Ritu Roy; Adam Olshen; Marilyn J. Hammer; Jon D. Levine; Christine Miaskowski

doi:10.1007/s00520-025-09317-9

Perturbations in the neuroactive ligand-receptor interaction and renin angiotensin system pathways are associated with cancer-related cognitive impairment

Raymond J. Chan, Adam Walker, Janette Vardy, Alexandre Chan, Kate Oppegaard, Yvette P. Conley, Steven M. Paul, Kord M. Kober, Carolyn Harris, Joosun Shin, Lisa Morse, Ritu Roy, Adam Olshen, Marilyn J. Hammer, Jon D. Levine, Christine Miaskowski

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Abstract

Purpose: This study reports on the results from our data-driven approach that identified perturbations in neuroactive ligand-receptor interaction and renin-angiotensin system (RAS) pathways in oncology patients with and without self-reported cancer-related cognitive impairment (CRCI).

Methods: In a sample of oncology patients receiving chemotherapy (n = 1343), the Attentional Function Index (AFI) was used to assess CRCI. Patients were grouped into low (AFI score of < 5) versus high (AFI score of > 7.5) levels of cognitive function. Gene expression analyses were done using RNA-seq (n = 185) and microarray (n = 158) technologies. Pathway impact analysis was used to evaluate for perturbations in biological pathways associated with self-reported CRCI.

Results: The combined pathway impact analysis revealed that the neuroactive ligand-receptor interaction and RAS pathways were significantly perturbed between the patients with low versus high AFI scores.

Conclusions: Findings from this study suggest that in addition to inflammatory pathways, numerous mechanisms may contribute to the underlying mechanisms for the development and/or persistence of self-reported CRCI.

Original language	English
Article number	254
Number of pages	9
Journal	Supportive Care in Cancer
Volume	33
Issue number	4
DOIs	https://doi.org/10.1007/s00520-025-09317-9
Publication status	Published - Apr 2025

Keywords

Cancer
Chemotherapy
Cognitive dysfunction
Cognitive impairment
Neuroinflammation
Renin angiotensin system

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Final published versionFinal published version, 519 KBLicence: CC BY

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Chan, R. J., Walker, A., Vardy, J., Chan, A., Oppegaard, K., Conley, Y. P., Paul, S. M., Kober, K. M., Harris, C., Shin, J., Morse, L., Roy, R., Olshen, A., Hammer, M. J., Levine, J. D., & Miaskowski, C. (2025). Perturbations in the neuroactive ligand-receptor interaction and renin angiotensin system pathways are associated with cancer-related cognitive impairment. Supportive Care in Cancer, 33(4), Article 254. https://doi.org/10.1007/s00520-025-09317-9

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title = "Perturbations in the neuroactive ligand-receptor interaction and renin angiotensin system pathways are associated with cancer-related cognitive impairment",

abstract = "Purpose: This study reports on the results from our data-driven approach that identified perturbations in neuroactive ligand-receptor interaction and renin-angiotensin system (RAS) pathways in oncology patients with and without self-reported cancer-related cognitive impairment (CRCI). Methods: In a sample of oncology patients receiving chemotherapy (n = 1343), the Attentional Function Index (AFI) was used to assess CRCI. Patients were grouped into low (AFI score of < 5) versus high (AFI score of > 7.5) levels of cognitive function. Gene expression analyses were done using RNA-seq (n = 185) and microarray (n = 158) technologies. Pathway impact analysis was used to evaluate for perturbations in biological pathways associated with self-reported CRCI. Results: The combined pathway impact analysis revealed that the neuroactive ligand-receptor interaction and RAS pathways were significantly perturbed between the patients with low versus high AFI scores. Conclusions: Findings from this study suggest that in addition to inflammatory pathways, numerous mechanisms may contribute to the underlying mechanisms for the development and/or persistence of self-reported CRCI.",

keywords = "Cancer, Chemotherapy, Cognitive dysfunction, Cognitive impairment, Neuroinflammation, Renin angiotensin system",

author = "Chan, {Raymond J.} and Adam Walker and Janette Vardy and Alexandre Chan and Kate Oppegaard and Conley, {Yvette P.} and Paul, {Steven M.} and Kober, {Kord M.} and Carolyn Harris and Joosun Shin and Lisa Morse and Ritu Roy and Adam Olshen and Hammer, {Marilyn J.} and Levine, {Jon D.} and Christine Miaskowski",

year = "2025",

month = apr,

doi = "10.1007/s00520-025-09317-9",

language = "English",

volume = "33",

journal = "Supportive Care in Cancer",

issn = "0941-4355",

publisher = "Springer Science and Business Media Deutschland GmbH",

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Chan, RJ, Walker, A, Vardy, J, Chan, A, Oppegaard, K, Conley, YP, Paul, SM, Kober, KM, Harris, C, Shin, J, Morse, L, Roy, R, Olshen, A, Hammer, MJ, Levine, JD & Miaskowski, C 2025, 'Perturbations in the neuroactive ligand-receptor interaction and renin angiotensin system pathways are associated with cancer-related cognitive impairment', Supportive Care in Cancer, vol. 33, no. 4, 254. https://doi.org/10.1007/s00520-025-09317-9

TY - JOUR

T1 - Perturbations in the neuroactive ligand-receptor interaction and renin angiotensin system pathways are associated with cancer-related cognitive impairment

AU - Chan, Raymond J.

AU - Walker, Adam

AU - Vardy, Janette

AU - Chan, Alexandre

AU - Oppegaard, Kate

AU - Conley, Yvette P.

AU - Paul, Steven M.

AU - Kober, Kord M.

AU - Harris, Carolyn

AU - Shin, Joosun

AU - Morse, Lisa

AU - Roy, Ritu

AU - Olshen, Adam

AU - Hammer, Marilyn J.

AU - Levine, Jon D.

AU - Miaskowski, Christine

PY - 2025/4

Y1 - 2025/4

N2 - Purpose: This study reports on the results from our data-driven approach that identified perturbations in neuroactive ligand-receptor interaction and renin-angiotensin system (RAS) pathways in oncology patients with and without self-reported cancer-related cognitive impairment (CRCI). Methods: In a sample of oncology patients receiving chemotherapy (n = 1343), the Attentional Function Index (AFI) was used to assess CRCI. Patients were grouped into low (AFI score of < 5) versus high (AFI score of > 7.5) levels of cognitive function. Gene expression analyses were done using RNA-seq (n = 185) and microarray (n = 158) technologies. Pathway impact analysis was used to evaluate for perturbations in biological pathways associated with self-reported CRCI. Results: The combined pathway impact analysis revealed that the neuroactive ligand-receptor interaction and RAS pathways were significantly perturbed between the patients with low versus high AFI scores. Conclusions: Findings from this study suggest that in addition to inflammatory pathways, numerous mechanisms may contribute to the underlying mechanisms for the development and/or persistence of self-reported CRCI.

AB - Purpose: This study reports on the results from our data-driven approach that identified perturbations in neuroactive ligand-receptor interaction and renin-angiotensin system (RAS) pathways in oncology patients with and without self-reported cancer-related cognitive impairment (CRCI). Methods: In a sample of oncology patients receiving chemotherapy (n = 1343), the Attentional Function Index (AFI) was used to assess CRCI. Patients were grouped into low (AFI score of < 5) versus high (AFI score of > 7.5) levels of cognitive function. Gene expression analyses were done using RNA-seq (n = 185) and microarray (n = 158) technologies. Pathway impact analysis was used to evaluate for perturbations in biological pathways associated with self-reported CRCI. Results: The combined pathway impact analysis revealed that the neuroactive ligand-receptor interaction and RAS pathways were significantly perturbed between the patients with low versus high AFI scores. Conclusions: Findings from this study suggest that in addition to inflammatory pathways, numerous mechanisms may contribute to the underlying mechanisms for the development and/or persistence of self-reported CRCI.

KW - Cancer

KW - Chemotherapy

KW - Cognitive dysfunction

KW - Cognitive impairment

KW - Neuroinflammation

KW - Renin angiotensin system

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U2 - 10.1007/s00520-025-09317-9

DO - 10.1007/s00520-025-09317-9

M3 - Article

C2 - 40047999

AN - SCOPUS:86000300285

SN - 0941-4355

VL - 33

JO - Supportive Care in Cancer

JF - Supportive Care in Cancer

IS - 4

M1 - 254

ER -

Perturbations in the neuroactive ligand-receptor interaction and renin angiotensin system pathways are associated with cancer-related cognitive impairment

Abstract

Keywords

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