Understanding Preanalytical Variables and Their Effects on Clinical Biomarkers of Oncology and Immunotherapy

Overview

Journal Semin Cancer Biol

Specialty Oncology

Date 2017 Dec 21

PMID 29258857

Citations 30

Authors

Lokesh Agrawal

Kelly B Engel

Sarah R Greytak

Helen M Moore

Affiliations

Soon will be listed here.

Abstract

Identifying a suitable course of immunotherapy treatment for a given patient as well as monitoring treatment response is heavily reliant on biomarkers detected and quantified in blood and tissue biospecimens. Suboptimal or variable biospecimen collection, processing, and storage practices have the potential to alter clinically relevant biomarkers, including those used in cancer immunotherapy. In the present review, we summarize effects reported for immunologically relevant biomarkers and highlight preanalytical factors associated with specific analytical platforms and assays used to predict and gauge immunotherapy response. Given that many of the effects introduced by preanalytical variability are gene-, transcript-, and protein-specific, biospecimen practices should be standardized and validated for each biomarker and assay to ensure accurate results and facilitate clinical implementation of newly identified immunotherapy approaches.

Citing Articles

Regulatory, Translational, and Operational Considerations for the Incorporation of Biomarkers in Drug Development.

Hatcher H, Stankeviciute S, Learn C, Qu A Ther Innov Regul Sci. 2025; .

PMID: 40057669 DOI: 10.1007/s43441-025-00763-5.

Canadian Consensus Recommendations for Predictive Biomarker Testing in Gastric and Gastroesophageal Junction Adenocarcinoma.

Brezden-Masley C, Fiset P, Cheung C, Arnason T, Bateman J, Borduas M Curr Oncol. 2024; 31(12):7770-7786.

PMID: 39727695 PMC: 11674259. DOI: 10.3390/curroncol31120572.

Analysis of DNA Methylation in Gliomas: Assessment of Preanalytical Variables.

Bomsztyk K, Mar D, Denisenko O, Powell S, Vishnoi M, Yin Z Lab Invest. 2024; 104(12):102160.

PMID: 39426568 PMC: 11709230. DOI: 10.1016/j.labinv.2024.102160.

Circulating tumour DNA analysis for early detection of lung cancer: a systematic review.

Lam W, Bai J, Ma M, Cheung Y, Jiang P Ann Transl Med. 2024; 12(4):64.

PMID: 39118954 PMC: 11304429. DOI: 10.21037/atm-23-1572.

Insight into the Functional Dynamics and Challenges of Exosomes in Pharmaceutical Innovation and Precision Medicine.

Sharma A, Yadav A, Nandy A, Ghatak S Pharmaceutics. 2024; 16(6).

PMID: 38931833 PMC: 11206934. DOI: 10.3390/pharmaceutics16060709.

References

Xie Q, Gao W, Li J, Qiao T, Jin J, Deng H . Correlation of cortisol in 1-cm hair segment with salivary cortisol in human: hair cortisol as an endogenous biomarker. Clin Chem Lab Med. 2011; 49(12):2013-9. DOI: 10.1515/CCLM.2011.706. View

Herbst R, Soria J, Kowanetz M, Fine G, Hamid O, Gordon M . Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014; 515(7528):563-7. PMC: 4836193. DOI: 10.1038/nature14011. View

Kalmar A, Peterfia B, Wichmann B, Patai A, Bartak B, Nagy Z . Comparison of Automated and Manual DNA Isolation Methods for DNA Methylation Analysis of Biopsy, Fresh Frozen, and Formalin-Fixed, Paraffin-Embedded Colorectal Cancer Samples. J Lab Autom. 2015; 20(6):642-51. DOI: 10.1177/2211068214565903. View

Nielsen T, Wallden B, Schaper C, Ferree S, Liu S, Gao D . Analytical validation of the PAM50-based Prosigna Breast Cancer Prognostic Gene Signature Assay and nCounter Analysis System using formalin-fixed paraffin-embedded breast tumor specimens. BMC Cancer. 2014; 14:177. PMC: 4008304. DOI: 10.1186/1471-2407-14-177. View

Grasselli J, Elez E, Caratu G, Matito J, Santos C, Macarulla T . Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer. Ann Oncol. 2017; 28(6):1294-1301. PMC: 5834108. DOI: 10.1093/annonc/mdx112. View

von Wasielewski R, Mengel M, Wiese B, Rudiger T, Muller-Hermelink H, Kreipe H . Tissue array technology for testing interlaboratory and interobserver reproducibility of immunohistochemical estrogen receptor analysis in a large multicenter trial. Am J Clin Pathol. 2002; 118(5):675-82. DOI: 10.1309/URLK-6AVK-331U-0V5P. View

Mittempergher L, de Ronde J, Nieuwland M, Kerkhoven R, Simon I, Rutgers E . Gene expression profiles from formalin fixed paraffin embedded breast cancer tissue are largely comparable to fresh frozen matched tissue. PLoS One. 2011; 6(2):e17163. PMC: 3037966. DOI: 10.1371/journal.pone.0017163. View

Olson W, Smolkin M, Farris E, Fink R, Czarkowski A, Fink J . Shipping blood to a central laboratory in multicenter clinical trials: effect of ambient temperature on specimen temperature, and effects of temperature on mononuclear cell yield, viability and immunologic function. J Transl Med. 2011; 9:26. PMC: 3063218. DOI: 10.1186/1479-5876-9-26. View

Pyo J, Kang G, Kim J . Prognostic role of PD-L1 in malignant solid tumors: a meta-analysis. Int J Biol Markers. 2016; 32(1):e68-e74. DOI: 10.5301/jbm.5000225. View

10.

Koberle V, Pleli T, Schmithals C, Augusto Alonso E, Haupenthal J, Bonig H . Differential stability of cell-free circulating microRNAs: implications for their utilization as biomarkers. PLoS One. 2013; 8(9):e75184. PMC: 3779196. DOI: 10.1371/journal.pone.0075184. View

11.

Chang F, Li M . Clinical application of amplicon-based next-generation sequencing in cancer. Cancer Genet. 2013; 206(12):413-9. DOI: 10.1016/j.cancergen.2013.10.003. View

12.

Beaulieu M, Desaulniers M, Bertrand N, Deschesnes R, Beaudry G, Garon G . Analytical performance of a qRT-PCR assay to detect guanylyl cyclase C in FFPE lymph nodes of patients with colon cancer. Diagn Mol Pathol. 2010; 19(1):20-7. DOI: 10.1097/PDM.0b013e3181ad5ac3. View

13.

lznerowicz A, Chudoba P, Kaminska D, Koscielska-Kasprzak K, Drulis-Fajdasz D, Halon A . Duration of brain death and cold ischemia time, but not warm ischemia time, increases expression of genes associated with apoptosis in transplanted kidneys from deceased donors. Transplant Proc. 2011; 43(8):2887-90. DOI: 10.1016/j.transproceed.2011.08.013. View

14.

de Jager W, Bourcier K, Rijkers G, Prakken B, Seyfert-Margolis V . Prerequisites for cytokine measurements in clinical trials with multiplex immunoassays. BMC Immunol. 2009; 10:52. PMC: 2761376. DOI: 10.1186/1471-2172-10-52. View

15.

Lippi G, Fortunato A, Salvagno G, Montagnana M, Soffiati G, Guidi G . Influence of sample matrix and storage on BNP measurement on the Bayer Advia Centaur. J Clin Lab Anal. 2007; 21(5):293-7. PMC: 6649196. DOI: 10.1002/jcla.20187. View

16.

Tuck M, Chan D, Chia D, Godwin A, Grizzle W, Krueger K . Standard operating procedures for serum and plasma collection: early detection research network consensus statement standard operating procedure integration working group. J Proteome Res. 2008; 8(1):113-7. PMC: 2655764. DOI: 10.1021/pr800545q. View

17.

Sparrow R, Chan K . Microparticle content of plasma for transfusion is influenced by the whole blood hold conditions: pre-analytical considerations for proteomic investigations. J Proteomics. 2012; 76 Spec No.:211-9. PMC: 4177036. DOI: 10.1016/j.jprot.2012.07.013. View

18.

Iwai Y, Hamanishi J, Chamoto K, Honjo T . Cancer immunotherapies targeting the PD-1 signaling pathway. J Biomed Sci. 2017; 24(1):26. PMC: 5381059. DOI: 10.1186/s12929-017-0329-9. View

19.

Yang Y, Li J, Jin L, Wang D, Zhang J, Wang J . Independent Correlation Between Ki67 Index and Circulating Tumor Cells in the Diagnosis of Colorectal Cancer. Anticancer Res. 2017; 37(8):4693-4700. DOI: 10.21873/anticanres.11874. View

20.

Azimi-Nezhad M, Lambert D, Ottone C, Perrin C, Chapel C, Gaillard G . Influence of pre-analytical variables on VEGF gene expression and circulating protein concentrations. Biopreserv Biobank. 2014; 10(5):454-61. DOI: 10.1089/bio.2012.0016. View