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01.03.2018 | Original Article

Differential expression of genes and differentially perturbed pathways associated with very high evening fatigue in oncology patients receiving chemotherapy

verfasst von: Elena Flowers, Christine Miaskowski, Yvette Conley, Marilyn J. Hammer, Jon Levine, Judy Mastick, Steven Paul, Fay Wright, Kord Kober

Erschienen in: Supportive Care in Cancer | Ausgabe 3/2018

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Abstract

Purpose

Fatigue is the most common symptom associated with cancer and its treatment. Investigation of molecular mechanisms associated with fatigue in oncology patients may identify new therapeutic targets. The objectives of this study were to evaluate the relationships between gene expression and perturbations in biological pathways and evening fatigue severity in oncology patients who received chemotherapy (CTX).

Methods

The Lee Fatigue Scale (LFS) and latent class analysis were used to identify evening fatigue phenotypes. We measured 47,214 ribonucleic acid transcripts from whole blood collected prior to a cycle of CTX. Perturbations in biological pathways associated with differential gene expression were identified from public data sets (i.e., Kyoto Encyclopedia Gene and Genomes, BioCarta).

Results

Patients were classified into Moderate (n = 65, mean LFS score 3.1) or Very High (n = 195, mean LFS score 6.4) evening fatigue groups. Compared to patients with Moderate fatigue, patients with Very High fatigue exhibited differential expression of 29 genes. A number of the perturbed pathways identified validated prior mechanistic hypotheses for fatigue, including alterations in immune function, inflammation, neurotransmission, energy metabolism, and circadian rhythms. Based on our findings, energy metabolism was further divided into alterations in carbohydrate metabolism and skeletal muscle energy. Alterations in renal function-related pathways were identified as a potential new mechanism.

Conclusions

This study identified differential gene expression and perturbed biological pathways that provide new insights into the multiple and likely inter-related mechanisms associated with evening fatigue in oncology patients.

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Berger AM, Gerber LH, Mayer DK (2012) Cancer-related fatigue: implications for breast cancer survivors. Cancer 118(8 Suppl):2261–2269. https://doi.org/10.1002/cncr.27475 CrossRefPubMed

Abrahams Y, Laguette MJ, Prince S, Collins M (2013) Polymorphisms within the COL5A1 3-UTR that alters mRNA structure and the MIR608 gene are associated with Achilles tendinopathy. Ann Hum Genet 77:204–214. https://doi.org/10.1111/ahg.12013 CrossRefPubMed

Bower JE, Ganz PA, Irwin MR, Arevalo JM, Cole SW (2011) Fatigue and gene expression in human leukocytes: increased NF-kappaB and decreased glucocorticoid signaling in breast cancer survivors with persistent fatigue. Brain Behav Immun 25(1):147–150. https://doi.org/10.1016/j.bbi.2010.09.010 CrossRefPubMed

Meneses-Echavez JF, Gonzalez-Jimenez E, Ramirez-Velez R (2015) Effects of supervised multimodal exercise interventions on cancer-related fatigue: systematic review and meta-analysis of randomized controlled trials. Biomed Res Int 2015:328636. https://doi.org/10.1155/2015/328636 CrossRefPubMedPubMedCentral

Tomlinson D, Diorio C, Beyene J, Sung L (2014) Effect of exercise on cancer-related fatigue: a meta-analysis. Am J Phys Med Rehabil 93(8):675–686. https://doi.org/10.1097/PHM.0000000000000083 CrossRefPubMed

Saligan LN, Kim HS (2012) A systematic review of the association between immunogenomic markers and cancer-related fatigue. Brain Behav Immun 26(6):830–848. https://doi.org/10.1016/j.bbi.2012.05.004 CrossRefPubMedPubMedCentral

Bower JE (2014) Cancer-related fatigue—mechanisms, risk factors, and treatments. Nat Rev Clin Oncol 11(10):597–609. https://doi.org/10.1038/nrclinonc.2014.127 CrossRefPubMedPubMedCentral

Barsevick A, Frost M, Zwinderman A, Hall P, Halyard M, Consortium G (2010) I’m so tired: biological and genetic mechanisms of cancer-related fatigue. Qual Life Res Int J Qual Life Asp Treat Care Rehab 19(10):1419–1427. https://doi.org/10.1007/s11136-010-9757-7

Landmark-Hoyvik H, Reinertsen KV, Loge JH, Kristensen VN, Dumeaux V, Fossa SD, Borresen-Dale AL, Edvardsen H (2010) The genetics and epigenetics of fatigue. PM R 2(5):456–465. https://doi.org/10.1016/j.pmrj.2010.04.003 CrossRefPubMed

10.

Saligan LN, Olson K, Filler K, Larkin D, Cramp F, Yennurajalingam S, Escalante CP, del Giglio A, Kober KM, Kamath J, Palesh O, Mustian K, Multinational Association of Supportive Care in Cancer Fatigue Study Group-Biomarker Working G (2015) The biology of cancer-related fatigue: a review of the literature. Support Care Cancer Off J Multinatl Assoc Supp Care Cancer 23(8):2461–2478. https://doi.org/10.1007/s00520-015-2763-0 CrossRef

11.

Kober KM, Dunn L, Mastick J, Cooper B, Langford D, Melisko M, Venook A, Chen LM, Wright F, Hammer M, Schmidt BL, Levine J, Miaskowski C, Aouizerat BE (2016) Gene expression profiling of evening fatigue in women undergoing chemotherapy for breast cancer. Biol Res Nurs. https://doi.org/10.1177/1099800416629209

12.

Hsiao CP, Reddy SY, Chen MK, Saligan LN (2016) Genomic profile of fatigued men receiving localized radiation therapy. Biol Res Nurs 18(3):281–289. https://doi.org/10.1177/1099800415618786 CrossRefPubMed

13.

Landmark-Hoyvik H, Reinertsen KV, Loge JH, Fossa SD, Borresen-Dale AL, Dumeaux V (2009) Alterations of gene expression in blood cells associated with chronic fatigue in breast cancer survivors. Pharmacogenomics J 9(5):333–340. https://doi.org/10.1038/tpj.2009.27 CrossRefPubMed

14.

Saligan LN, Hsiao CP, Wang D, Wang XM, St John L, Kaushal A, Citrin D, Barb JJ, Munson PJ, Dionne RA (2013) Upregulation of alpha-synuclein during localized radiation therapy signals the association of cancer-related fatigue with the activation of inflammatory and neuroprotective pathways. Brain Behav Immun 27(1):63–70. https://doi.org/10.1016/j.bbi.2012.09.009 CrossRefPubMed

15.

Miaskowski C, Dunn L, Ritchie C, Paul SM, Cooper B, Aouizerat BE, Alexander K, Skerman H, Yates P (2015) Latent class analysis reveals distinct subgroups of patients based on symptom occurrence and demographic and clinical characteristics. J Pain Symptom Manag 50(1):28–37. https://doi.org/10.1016/j.jpainsymman.2014.12.011 CrossRef

16.

Kober KM, Cooper BA, Paul SM, Dunn LB, Levine JD, Wright F, Hammer MJ, Mastick J, Venook A, Aouizerat BE, Miaskowski C (2016) Subgroups of chemotherapy patients with distinct morning and evening fatigue trajectories. Support Care Cancer Off J Multinatl Assoc Supp Care Cancer 24(4):1473–1485. https://doi.org/10.1007/s00520-015-2895-2 CrossRef

17.

Karnofsky DA, Abelmann HW, Craver LV, Burchenal JH (1948) The use of nitrogen mustards in the palliative treatment of carcinoma. Cancer 1:634–656CrossRef

18.

Sangha O, Stucki G, Liang MH, Fossel AH, Katz JN (2003) The Self-Administered Comorbidity Questionnaire: a new method to assess comorbidity for clinical and health services research. Arthritis Rheum 49(2):156–163. https://doi.org/10.1002/art.10993 CrossRefPubMed

19.

Lee KA, Hicks G, Nino-Murcia G (1991) Validity and reliability of a scale to assess fatigue. Psychiatry Res 36(3):291–298CrossRefPubMed

20.

Fletcher BS, Paul SM, Dodd MJ, Schumacher K, West C, Cooper B, Lee K, Aouizerat B, Swift P, Wara W, Miaskowski CA (2008) Prevalence, severity, and impact of symptoms on female family caregivers of patients at the initiation of radiation therapy for prostate cancer. J clinical Oncol Off J Am Soc Clin Oncol 26(4):599–605. https://doi.org/10.1200/JCO.2007.12.2838 CrossRef

21.

Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini AJ, Sawitzki G, Smith C, Smyth G, Tierney L, Yang JY, Zhang J (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5(10):R80. https://doi.org/10.1186/gb-2004-5-10-r80 CrossRefPubMedPubMedCentral

22.

Smyth G (2005) Limma: linear models for microarray data. Springer, New York

23.

Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK (2015) Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 43(7):e47. https://doi.org/10.1093/nar/gkv007 CrossRefPubMedPubMedCentral

24.

Hochberg Y, Benjamini Y (1990) More powerful procedures for multiple significance testing. Stat Med 9(7):811–818CrossRefPubMed

25.

Matys V, Kel-Margoulis OV, Fricke E, Liebich I, Land S, Barre-Dirrie A, Reuter I, Chekmenev D, Krull M, Hornischer K, Voss N, Stegmaier P, Lewicki-Potapov B, Saxel H, Kel AE, Wingender E (2006) TRANSFAC and its module TRANSCompel: transcriptional gene regulation in eukaryotes. Nucleic Acids Res 34(Database issue):D108–D110. https://doi.org/10.1093/nar/gkj143 CrossRefPubMed

26.

Weirauch MT, Yang A, Albu M, Cote AG, Montenegro-Montero A, Drewe P, Najafabadi HS, Lambert SA, Mann I, Cook K, Zheng H, Goity A, van Bakel H, Lozano JC, Galli M, Lewsey MG, Huang E, Mukherjee T, Chen X, Reece-Hoyes JS, Govindarajan S, Shaulsky G, Walhout AJ, Bouget FY, Ratsch G, Larrondo LF, Ecker JR, Hughes TR (2014) Determination and inference of eukaryotic transcription factor sequence specificity. Cell 158(6):1431–1443. https://doi.org/10.1016/j.cell.2014.08.009 CrossRefPubMedPubMedCentral

27.

Harris MA, Clark J, Ireland A, Lomax J, Ashburner M, Foulger R, Eilbeck K, Lewis S, Marshall B, Mungall C, Richter J, Rubin GM, Blake JA, Bult C, Dolan M, Drabkin H, Eppig JT, Hill DP, Ni L, Ringwald M, Balakrishnan R, Cherry JM, Christie KR, Costanzo MC, Dwight SS, Engel S, Fisk DG, Hirschman JE, Hong EL, Nash RS, Sethuraman A, Theesfeld CL, Botstein D, Dolinski K, Feierbach B, Berardini T, Mundodi S, Rhee SY, Apweiler R, Barrell D, Camon E, Dimmer E, Lee V, Chisholm R, Gaudet P, Kibbe W, Kishore R, Schwarz EM, Sternberg P, Gwinn M, Hannick L, Wortman J, Berriman M, Wood V, de la Cruz N, Tonellato P, Jaiswal P, Seigfried T, White R, Gene Ontology C (2004) The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res 32(Database issue):D258–D261. https://doi.org/10.1093/nar/gkh036 PubMed

28.

Reimers M (2010) Making informed choices about microarray data analysis. PLoS Comput Biol 6(5):e1000786. https://doi.org/10.1371/journal.pcbi.1000786 CrossRefPubMedPubMedCentral

29.

Luo W, Friedman MS, Shedden K, Hankenson KD, Woolf PJ (2009) GAGE: generally applicable gene set enrichment for pathway analysis. BMC Bioinf 10:161. https://doi.org/10.1186/1471-2105-10-161 CrossRef

30.

Tripathi S, Glazko GV, Emmert-Streib F (2013) Ensuring the statistical soundness of competitive gene set approaches: gene filtering and genome-scale coverage are essential. Nucleic Acids Res 41(7):e82. https://doi.org/10.1093/nar/gkt054 CrossRefPubMedPubMedCentral

31.

Aoki-Kinoshita KF, Kanehisa M (2007) Gene annotation and pathway mapping in KEGG. Methods Mol Biol 396:71–91. https://doi.org/10.1007/978-1-59745-515-2_6 CrossRefPubMed

32.

Nishimura D (2001) BioCarta. Biotechnol Softw Internet Rep 2:117–120CrossRef

33.

Engreitz JM, Morgan AA, Dudley JT, Chen R, Thathoo R, Altman RB, Butte AJ (2010) Content-based microarray search using differential expression profiles. BMC Bioinf 11:603. https://doi.org/10.1186/1471-2105-11-603 CrossRef

34.

Syed NA, Andersen PL, Warrington RC, Xiao W (2006) Uev1A, a ubiquitin conjugating enzyme variant, inhibits stress-induced apoptosis through NF-kappaB activation. Apoptosis Int J Programmed Cell Death 11(12):2147–2157. https://doi.org/10.1007/s10495-006-0197-3 CrossRef

35.

Gale DP, Pickering MC (2011) Regulating complement in the kidney: insights from CFHR5 nephropathy. Dis Model Mech 4(6):721–726. https://doi.org/10.1242/dmm.008052 CrossRefPubMedPubMedCentral

36.

Abrera-Abeleda MA, Nishimura C, Smith JL, Sethi S, McRae JL, Murphy BF, Silvestri G, Skerka C, Jozsi M, Zipfel PF, Hageman GS, Smith RJ (2006) Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with membranoproliferative glomerulonephritis type II (dense deposit disease). J Med Genet 43(7):582–589. https://doi.org/10.1136/jmg.2005.038315 CrossRefPubMed

37.

Gharavi AG, Kiryluk K, Choi M, Li Y, Hou P, Xie J, Sanna-Cherchi S, Men CJ, Julian BA, Wyatt RJ, Novak J, He JC, Wang H, Lv J, Zhu L, Wang W, Wang Z, Yasuno K, Gunel M, Mane S, Umlauf S, Tikhonova I, Beerman I, Savoldi S, Magistroni R, Ghiggeri GM, Bodria M, Lugani F, Ravani P, Ponticelli C, Allegri L, Boscutti G, Frasca G, Amore A, Peruzzi L, Coppo R, Izzi C, Viola BF, Prati E, Salvadori M, Mignani R, Gesualdo L, Bertinetto F, Mesiano P, Amoroso A, Scolari F, Chen N, Zhang H, Lifton RP (2011) Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nat Genet 43(4):321–327. https://doi.org/10.1038/ng.787 CrossRefPubMedPubMedCentral

38.

Basler M, Buerger S, Groettrup M (2015) The ubiquitin-like modifier FAT10 in antigen processing and antimicrobial defense. Mol Immunol 68(2 Pt A):129–132. https://doi.org/10.1016/j.molimm.2015.04.012 CrossRefPubMed

39.

Makari-Judson G, Katz D, Barham R, Mertens W (2009) Deleterious effect of chemotherapy on measures of insulin resistance in patients with newly-diagnosed invasive breast cancer. Cancer Res 69(24 Supplement):1054. https://doi.org/10.1158/0008-5472.sabcs-09-1054 CrossRef

40.

Trombetta M, Bonetti S, Boselli M, Turrini F, Malerba G, Trabetti E, Pignatti P, Bonora E, Bonadonna RC (2012) CACNA1E variants affect beta cell function in patients with newly diagnosed type 2 diabetes. The Verona newly diagnosed type 2 diabetes study (VNDS) 3. PLoS One 7(3):e32755. https://doi.org/10.1371/journal.pone.0032755 CrossRefPubMedPubMedCentral

41.

Holmkvist J, Tojjar D, Almgren P, Lyssenko V, Lindgren CM, Isomaa B, Tuomi T, Berglund G, Renstrom E, Groop L (2007) Polymorphisms in the gene encoding the voltage-dependent Ca(2+) channel Ca (V)2.3 (CACNA1E) are associated with type 2 diabetes and impaired insulin secretion. Diabetologia 50(12):2467–2475. https://doi.org/10.1007/s00125-007-0846-2 CrossRefPubMed

42.

Brown AE, Palsgaard J, Borup R, Avery P, Gunn DA, De Meyts P, Yeaman SJ, Walker M (2015) p38 MAPK activation upregulates proinflammatory pathways in skeletal muscle cells from insulin-resistant type 2 diabetic patients. Am J Phys Endocrinol Metab 308(1):E63–E70. https://doi.org/10.1152/ajpendo.00115.2014 CrossRef

43.

Roura-Ferrer M, Etxebarria A, Sole L, Oliveras A, Comes N, Villarroel A, Felipe A (2009) Functional implications of KCNE subunit expression for the Kv7.5 (KCNQ5) channel. Cell Physiol Biochem 24(5–6):325–334. https://doi.org/10.1159/000257425 CrossRefPubMed

44.

Amro A, Waldum-Grevbo B, von der Lippe N, Brekke FB, Miaskowski C, Os I (2016) Symptom clusters from dialysis to renal transplantation: a five-year longitudinal study. J Pain Symptom Manag 51(3):512–519. https://doi.org/10.1016/j.jpainsymman.2015.10.012 CrossRef

45.

Kwak SM, Choi YS, Yoon HM, Kim DG, Song SH, Lee YJ, Yeom CH, Koh SJ, Park J, Lee MA, Suh SY (2012) The relationship between interleukin-6, tumor necrosis factor-alpha, and fatigue in terminally ill cancer patients. Palliat Med 26(3):275–282. https://doi.org/10.1177/0269216311406991 CrossRefPubMed

46.

Romanic AM, Burns-Kurtis CL, Ao Z, Arleth AJ, Ohlstein EH (2001) Upregulated expression of human membrane type-5 matrix metalloproteinase in kidneys from diabetic patients. Am J Physiol Renal Physiol 281(2):F309–F317CrossRefPubMed

47.

Bower JE, Lamkin DM (2013) Inflammation and cancer-related fatigue: mechanisms, contributing factors, and treatment implications. Brain Behav Immun 30:S48–S57. https://doi.org/10.1016/j.bbi.2012.06.011 CrossRefPubMed

Titel: Differential expression of genes and differentially perturbed pathways associated with very high evening fatigue in oncology patients receiving chemotherapy
verfasst von: Elena Flowers
Christine Miaskowski
Yvette Conley
Marilyn J. Hammer
Jon Levine
Judy Mastick
Steven Paul
Fay Wright
Kord Kober
Publikationsdatum: 01.03.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Supportive Care in Cancer / Ausgabe 3/2018
Print ISSN: 0941-4355
Elektronische ISSN: 1433-7339
DOI: https://doi.org/10.1007/s00520-017-3883-5

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Springer Medizin

Differential expression of genes and differentially perturbed pathways associated with very high evening fatigue in oncology patients receiving chemotherapy

Abstract

Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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