Skip to main content
Top
Published in: Annals of Surgical Oncology 12/2018

01-11-2018 | Translational Research and Biomarkers

Tumor Cell Content and RNA Integrity of Surgical Tissues from Different Types of Tumors and Its Correlation with Ex Vivo and In Vivo Ischemia

Authors: Xiao-Hui Zheng, PhD, Shao-Dan Zhang, MS, Pei-Fen Zhang, MS, Xi-Zhao Li, MS, Ye-Zhu Hu, MS, Tian Tian, MS, Lin Zhu, PhD, Ruo-Zheng Wang, MD, PhD, Wei-Hua Jia, MD, PhD

Published in: Annals of Surgical Oncology | Issue 12/2018

Login to get access

Abstract

Background

Tissues from tumor patients are important resources for promoting cancer research, and therefore many biobanks have been established to collect tumor tissues; however, the quality of tumor tissues after surgical resection has not been well documented.

Methods

A total of 896 cases of tissues from 12 types of tumors were chosen for this study. First, histopathological examination was conducted to evaluate the tumor cell content; second, microchip electrophoresis was used to determine the RNA integrity number (RIN) in 466 cases of tissues with a tumor cell content ≥ 75%; and, finally, a correlation test was used to analyze the effect of ischemia on RNA integrity in 384 cases of tissues with a recorded ischemia time.

Results

Tumor tissues from 12 different organs had different tumor cell contents and RNA integrity. The liver had the highest percentage (69.7%) of tissue samples with a tumor cell content ≥ 75%, and the highest percentage (96%) of samples with an RIN ≥ 7. RNA integrity was not correlated with limited ex vivo ischemia time (5–60 min) in any of the 12 types of tumors. In contrast, a significant correlation with in vivo ischemia time was observed in several types of tumors.

Conclusions

Not every sample of excised tumor tissue has a sufficient amount of tumor cells and enough RNA integrity. In vivo ischemia has a more significant influence on RNA integrity, and tumor tissues have different tolerances to pre-analytical variables. Those conducting translational research should pay attention to pre-analytical variables when collecting and utilizing tumor tissues.
Appendix
Available only for authorised users
Literature
1.
go back to reference Garman KS, Nevins JR, Potti A. Genomic strategies for personalized cancer therapy. Hum Mol Genet 2007;16 Spec No. 2:R226–232.CrossRef Garman KS, Nevins JR, Potti A. Genomic strategies for personalized cancer therapy. Hum Mol Genet 2007;16 Spec No. 2:R226–232.CrossRef
2.
go back to reference Watson RW, Kay EW, Smith D. Integrating biobanks: addressing the practical and ethical issues to deliver a valuable tool for cancer research. Nat Rev Cancer. 2010;10:646–51.CrossRef Watson RW, Kay EW, Smith D. Integrating biobanks: addressing the practical and ethical issues to deliver a valuable tool for cancer research. Nat Rev Cancer. 2010;10:646–51.CrossRef
3.
go back to reference Vaught J, Rogers J, Myers K, et al. An NCI perspective on creating sustainable biospecimen resources. J Natl Cancer Inst Monogr. 2011;2011:1–7.CrossRef Vaught J, Rogers J, Myers K, et al. An NCI perspective on creating sustainable biospecimen resources. J Natl Cancer Inst Monogr. 2011;2011:1–7.CrossRef
4.
go back to reference Whyte B. National tumor bank set up in United Kingdom. J Natl Cancer Inst. 2003;95(10):706.CrossRef Whyte B. National tumor bank set up in United Kingdom. J Natl Cancer Inst. 2003;95(10):706.CrossRef
5.
go back to reference LiVolsi VA, Clausen KP, Grizzle W, Newton W, Pretlow TG 2nd, Aamodt R. The cooperative human tissue network. An update. Cancer. 1993;71:1391–94.PubMed LiVolsi VA, Clausen KP, Grizzle W, Newton W, Pretlow TG 2nd, Aamodt R. The cooperative human tissue network. An update. Cancer. 1993;71:1391–94.PubMed
6.
go back to reference Myles R, Massett HA, Comey G, Atkinson N, Allsop D, Compton C. Stakeholder research on biospecimen needs and reactions to the development of a national cancer human biobank by the National Cancer Institute. J Natl Cancer Inst Monogr. 2011;2011:16–23.CrossRef Myles R, Massett HA, Comey G, Atkinson N, Allsop D, Compton C. Stakeholder research on biospecimen needs and reactions to the development of a national cancer human biobank by the National Cancer Institute. J Natl Cancer Inst Monogr. 2011;2011:16–23.CrossRef
7.
go back to reference Le Bastard N, De Deyn PP, Engelborghs S. Importance and impact of preanalytical variables on Alzheimer disease biomarker concentrations in cerebrospinal fluid. Clin Chem. 2015;61:734–43.CrossRef Le Bastard N, De Deyn PP, Engelborghs S. Importance and impact of preanalytical variables on Alzheimer disease biomarker concentrations in cerebrospinal fluid. Clin Chem. 2015;61:734–43.CrossRef
8.
go back to reference Ellervik C, Vaught J. Preanalytical variables affecting the integrity of human biospecimens in biobanking. Clin Chem. 2015;61:914–34.CrossRef Ellervik C, Vaught J. Preanalytical variables affecting the integrity of human biospecimens in biobanking. Clin Chem. 2015;61:914–34.CrossRef
9.
go back to reference Moore HM. The NCI biospecimen research network. Biotech Histochem. 2012;87:18–23.CrossRef Moore HM. The NCI biospecimen research network. Biotech Histochem. 2012;87:18–23.CrossRef
10.
go back to reference Huang J, Qi R, Quackenbush J, Dauway E, Lazaridis E, Yeatman T. Effects of ischemia on gene expression. J Surg Res. 2001;99:222–27.CrossRef Huang J, Qi R, Quackenbush J, Dauway E, Lazaridis E, Yeatman T. Effects of ischemia on gene expression. J Surg Res. 2001;99:222–27.CrossRef
11.
go back to reference Spruessel A, Steimann G, Jung M, et al. Tissue ischemia time affects gene and protein expression patterns within minutes following surgical tumor excision. Biotechniques. 2004;36:1030–37.CrossRef Spruessel A, Steimann G, Jung M, et al. Tissue ischemia time affects gene and protein expression patterns within minutes following surgical tumor excision. Biotechniques. 2004;36:1030–37.CrossRef
12.
go back to reference Imbeaud S, Graudens E, Boulanger V, et al. Towards standardization of RNA quality assessment using user-independent classifiers of microcapillary electrophoresis traces. Nucl Acids Res. 2005;33:e56.CrossRef Imbeaud S, Graudens E, Boulanger V, et al. Towards standardization of RNA quality assessment using user-independent classifiers of microcapillary electrophoresis traces. Nucl Acids Res. 2005;33:e56.CrossRef
13.
go back to reference Morente MM, Mager R, Alonso S, et al. TuBaFrost 2: standardising tissue collection and quality control procedures for a European virtual frozen tissue bank network. Eur J Cancer. 2006;42:2684–91.CrossRef Morente MM, Mager R, Alonso S, et al. TuBaFrost 2: standardising tissue collection and quality control procedures for a European virtual frozen tissue bank network. Eur J Cancer. 2006;42:2684–91.CrossRef
14.
go back to reference Schroeder A, Mueller O, Stocker S, et al. The RIN: an RNA integrity number for assigning integrity values to RNA measurements. BMC Mol Biol. 2006;7:3.CrossRef Schroeder A, Mueller O, Stocker S, et al. The RIN: an RNA integrity number for assigning integrity values to RNA measurements. BMC Mol Biol. 2006;7:3.CrossRef
15.
go back to reference Mager SR, Oomen MH, Morente MM, et al. Standard operating procedure for the collection of fresh frozen tissue samples. Eur J Cancer. 2007;43:828–34.CrossRef Mager SR, Oomen MH, Morente MM, et al. Standard operating procedure for the collection of fresh frozen tissue samples. Eur J Cancer. 2007;43:828–34.CrossRef
16.
go back to reference Sun H, Sun R, Hao M, Wang Y, Zhang X, Liu Y, et al. Effect of duration of ex vivo ischemia time and storage period on RNA quality in biobanked human renal cell carcinoma tissue. Ann Surg Oncol. 2016;23:297–304.CrossRef Sun H, Sun R, Hao M, Wang Y, Zhang X, Liu Y, et al. Effect of duration of ex vivo ischemia time and storage period on RNA quality in biobanked human renal cell carcinoma tissue. Ann Surg Oncol. 2016;23:297–304.CrossRef
17.
go back to reference Lee SM, Schelcher C, Thasler R, Schiergens TS, Thasler WE. Pre-analytical determination of the effect of extended warm or cold ischaemia on RNA stability in the human ileum mucosa. PLoS ONE. 2015;10:e0138214.CrossRef Lee SM, Schelcher C, Thasler R, Schiergens TS, Thasler WE. Pre-analytical determination of the effect of extended warm or cold ischaemia on RNA stability in the human ileum mucosa. PLoS ONE. 2015;10:e0138214.CrossRef
18.
go back to reference Liu NW, Sanford T, Srinivasan R, et al. Impact of ischemia and procurement conditions on gene expression in renal cell carcinoma. Clin Cancer Res. 2013;19:42–9.CrossRef Liu NW, Sanford T, Srinivasan R, et al. Impact of ischemia and procurement conditions on gene expression in renal cell carcinoma. Clin Cancer Res. 2013;19:42–9.CrossRef
19.
go back to reference Lee SM, Schelcher C, Gashi S, Schreiber S, Thasler RM, Jauch KW, et al. RNA stability in human liver: comparison of different processing times, temperatures and methods. Mol Biotechnol. 2013;53:1–8.CrossRef Lee SM, Schelcher C, Gashi S, Schreiber S, Thasler RM, Jauch KW, et al. RNA stability in human liver: comparison of different processing times, temperatures and methods. Mol Biotechnol. 2013;53:1–8.CrossRef
20.
go back to reference Bao WG, Zhang X, Zhang JG, et al. Biobanking of fresh-frozen human colon tissues: impact of tissue ex vivo ischemia times and storage periods on RNA quality. Ann Surg Oncol. 2013;20:1737–44.CrossRef Bao WG, Zhang X, Zhang JG, et al. Biobanking of fresh-frozen human colon tissues: impact of tissue ex vivo ischemia times and storage periods on RNA quality. Ann Surg Oncol. 2013;20:1737–44.CrossRef
21.
go back to reference Musella V, Verderio P, Reid JF, et al. Effects of warm ischemic time on gene expression profiling in colorectal cancer tissues and normal mucosa. PLoS ONE. 2013;8:e53406.CrossRef Musella V, Verderio P, Reid JF, et al. Effects of warm ischemic time on gene expression profiling in colorectal cancer tissues and normal mucosa. PLoS ONE. 2013;8:e53406.CrossRef
22.
go back to reference Hatzis C, Sun H, Yao H, et al. Effects of tissue handling on RNA integrity and microarray measurements from resected breast cancers. J Natl Cancer Inst. 2011;103:1871–83.CrossRef Hatzis C, Sun H, Yao H, et al. Effects of tissue handling on RNA integrity and microarray measurements from resected breast cancers. J Natl Cancer Inst. 2011;103:1871–83.CrossRef
23.
go back to reference Rudloff U, Bhanot U, Gerald W, et al. Biobanking of human pancreas cancer tissue: impact of ex vivo procurement times on RNA quality. Ann Surg Oncol. 2010;17:2229–36.CrossRef Rudloff U, Bhanot U, Gerald W, et al. Biobanking of human pancreas cancer tissue: impact of ex vivo procurement times on RNA quality. Ann Surg Oncol. 2010;17:2229–36.CrossRef
24.
go back to reference Hong SH, Baek HA, Jang KY, et al. Effects of delay in the snap freezing of colorectal cancer tissues on the quality of DNA and RNA. J Korean Soc Coloproctol. 2010;26:316–23.CrossRef Hong SH, Baek HA, Jang KY, et al. Effects of delay in the snap freezing of colorectal cancer tissues on the quality of DNA and RNA. J Korean Soc Coloproctol. 2010;26:316–23.CrossRef
25.
go back to reference Bray SE, Paulin FE, Fong SC, et al. Gene expression in colorectal neoplasia: modifications induced by tissue ischaemic time and tissue handling protocol. Histopathology. 2010;56:240–50.CrossRef Bray SE, Paulin FE, Fong SC, et al. Gene expression in colorectal neoplasia: modifications induced by tissue ischaemic time and tissue handling protocol. Histopathology. 2010;56:240–50.CrossRef
26.
go back to reference De Cecco L, Musella V, Veneroni S, et al. Impact of biospecimens handling on biomarker research in breast cancer. BMC Cancer. 2009;9:409.CrossRef De Cecco L, Musella V, Veneroni S, et al. Impact of biospecimens handling on biomarker research in breast cancer. BMC Cancer. 2009;9:409.CrossRef
27.
go back to reference Micke P, Ohshima M, Tahmasebpoor S, Ren ZP, Ostman A, Ponten F, et al. Biobanking of fresh frozen tissue: RNA is stable in nonfixed surgical specimens. Lab Invest. 2006;86:202–11.CrossRef Micke P, Ohshima M, Tahmasebpoor S, Ren ZP, Ostman A, Ponten F, et al. Biobanking of fresh frozen tissue: RNA is stable in nonfixed surgical specimens. Lab Invest. 2006;86:202–11.CrossRef
28.
go back to reference Guerrera F, Tabbo F, Bessone L, et al. The influence of tissue ischemia time on RNA integrity and patient-derived xenografts (PDX) engraftment rate in a non-small cell lung cancer (NSCLC) biobank. PLoS ONE. 2016;11:e0145100.CrossRef Guerrera F, Tabbo F, Bessone L, et al. The influence of tissue ischemia time on RNA integrity and patient-derived xenografts (PDX) engraftment rate in a non-small cell lung cancer (NSCLC) biobank. PLoS ONE. 2016;11:e0145100.CrossRef
29.
go back to reference Galissier T, Schneider C, Nasri S, et al. Biobanking of fresh-frozen human adenocarcinomatous and normal colon tissues: which parameters influence RNA quality? PLoS ONE. 2016;11:e0154326.CrossRef Galissier T, Schneider C, Nasri S, et al. Biobanking of fresh-frozen human adenocarcinomatous and normal colon tissues: which parameters influence RNA quality? PLoS ONE. 2016;11:e0154326.CrossRef
30.
go back to reference Sandusky GE, Teheny KH, Esterman M, Hanson J, Williams SD. Quality control of human tissues: experience from the Indiana University Cancer Center-Lilly Research Labs human tissue bank. Cell Tissue Bank. 2007;8:287–95.CrossRef Sandusky GE, Teheny KH, Esterman M, Hanson J, Williams SD. Quality control of human tissues: experience from the Indiana University Cancer Center-Lilly Research Labs human tissue bank. Cell Tissue Bank. 2007;8:287–95.CrossRef
31.
go back to reference Li H, Guo Y, Sun B, Chen K. Histological assessment of tumor tissue samples via the mirror image method. Biopreserv Biobank. 2015;13:25–30.CrossRef Li H, Guo Y, Sun B, Chen K. Histological assessment of tumor tissue samples via the mirror image method. Biopreserv Biobank. 2015;13:25–30.CrossRef
33.
go back to reference Ibberson D, Benes V, Muckenthaler MU, Castoldi M. RNA degradation compromises the reliability of microRNA expression profiling. BMC Biotechnol. 2009;9:102.CrossRef Ibberson D, Benes V, Muckenthaler MU, Castoldi M. RNA degradation compromises the reliability of microRNA expression profiling. BMC Biotechnol. 2009;9:102.CrossRef
34.
go back to reference Lee J, Hever A, Willhite D, Zlotnik A, Hevezi P. Effects of RNA degradation on gene expression analysis of human postmortem tissues. FASEB J. 2005;19:1356–58.CrossRef Lee J, Hever A, Willhite D, Zlotnik A, Hevezi P. Effects of RNA degradation on gene expression analysis of human postmortem tissues. FASEB J. 2005;19:1356–58.CrossRef
35.
go back to reference Viana CR, Neto CS, Kerr LM, et al. The interference of cold ischemia time in the quality of total RNA from frozen tumor samples. Cell Tissue Bank. 2013;14:167–73.CrossRef Viana CR, Neto CS, Kerr LM, et al. The interference of cold ischemia time in the quality of total RNA from frozen tumor samples. Cell Tissue Bank. 2013;14:167–73.CrossRef
36.
go back to reference Zeugner S, Mayr T, Zietz C, Aust DE, Baretton GB. RNA quality in fresh-frozen gastrointestinal tumor specimens-experiences from the tumor and healthy tissue bank TU Dresden. Recent Results Cancer Res. 2015;199:85–93.CrossRef Zeugner S, Mayr T, Zietz C, Aust DE, Baretton GB. RNA quality in fresh-frozen gastrointestinal tumor specimens-experiences from the tumor and healthy tissue bank TU Dresden. Recent Results Cancer Res. 2015;199:85–93.CrossRef
37.
go back to reference Ma Y, Dai H, Kong X. Impact of warm ischemia on gene expression analysis in surgically removed biosamples. Anal Biochem. 2012;423:229–35.CrossRef Ma Y, Dai H, Kong X. Impact of warm ischemia on gene expression analysis in surgically removed biosamples. Anal Biochem. 2012;423:229–35.CrossRef
38.
go back to reference Fajardy I, Moitrot E, Vambergue A, Vandersippe-Millot M, Deruelle P, Rousseaux J. Time course analysis of RNA stability in human placenta. BMC Mol Biol. 2009;10:21.CrossRef Fajardy I, Moitrot E, Vambergue A, Vandersippe-Millot M, Deruelle P, Rousseaux J. Time course analysis of RNA stability in human placenta. BMC Mol Biol. 2009;10:21.CrossRef
39.
go back to reference Abrahamsen HN, Steiniche T, Nexo E, Hamilton-Dutoit SJ, Sorensen BS. Towards quantitative mRNA analysis in paraffin-embedded tissues using real-time reverse transcriptase-polymerase chain reaction: a methodological study on lymph nodes from melanoma patients. J Mol Diagn. 2003;5:34–41.CrossRef Abrahamsen HN, Steiniche T, Nexo E, Hamilton-Dutoit SJ, Sorensen BS. Towards quantitative mRNA analysis in paraffin-embedded tissues using real-time reverse transcriptase-polymerase chain reaction: a methodological study on lymph nodes from melanoma patients. J Mol Diagn. 2003;5:34–41.CrossRef
40.
go back to reference Betsou F, Lehmann S, Ashton G, et al. Standard preanalytical coding for biospecimens: defining the sample PREanalytical code. Cancer Epidemiol Biomarkers Prev. 2010;19:1004–11.CrossRef Betsou F, Lehmann S, Ashton G, et al. Standard preanalytical coding for biospecimens: defining the sample PREanalytical code. Cancer Epidemiol Biomarkers Prev. 2010;19:1004–11.CrossRef
41.
go back to reference Moore HM, Kelly AB, Jewell SD, et al. Biospecimen reporting for improved study quality (BRISQ). Cancer Cytopathol. 2011;119:92–101.CrossRef Moore HM, Kelly AB, Jewell SD, et al. Biospecimen reporting for improved study quality (BRISQ). Cancer Cytopathol. 2011;119:92–101.CrossRef
Metadata
Title
Tumor Cell Content and RNA Integrity of Surgical Tissues from Different Types of Tumors and Its Correlation with Ex Vivo and In Vivo Ischemia
Authors
Xiao-Hui Zheng, PhD
Shao-Dan Zhang, MS
Pei-Fen Zhang, MS
Xi-Zhao Li, MS
Ye-Zhu Hu, MS
Tian Tian, MS
Lin Zhu, PhD
Ruo-Zheng Wang, MD, PhD
Wei-Hua Jia, MD, PhD
Publication date
01-11-2018
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 12/2018
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-018-6697-x

Other articles of this Issue 12/2018

Annals of Surgical Oncology 12/2018 Go to the issue