Molecular spectroscopy of blood plasma – towards the diagnostics of pancreatic cancer?
Authors:
B. Bunganič 1; L. Šťovíčková 2; M. Tatarkovič 2; L. Kocourková 2; Š. Suchánek 1; P. Frič 1; V. Setnička 2; M. Zavoral 1
Authors‘ workplace:
Interní klinika 1. LF UK a ÚVN – VFN v Praze
1; Ústav analytické chemie, VŠCHT v Praze
2
Published in:
Gastroent Hepatol 2015; 69(6): 518-524
Category:
Gastrointestinal Oncology: Original Article
doi:
https://doi.org/10.14735/amgh2015518
Overview
Pancreatic cancer is a malignancy with a poor prognosis and is estimated to become one of the leading causes of death from cancer by the end of the decade. Only early diagnosis may alter this adverse trend. To select a group of patients at risk of pancreatic cancer, an effective biomarker is required. The main objective of the pilot study is to identify a new specific spectral biomarker of pancreatic cancer using unpolarized methods of molecular spectroscopy (Raman spectroscopy) in combination with chiroptical methods that are inherently sensitive to structural changes of chiral molecules (electronic circular dichroism and Raman optical activity).
Methods:
Blood samples were collected from 10 patients with pancreatic cancer and 23 healthy controls. Subsequently, blood plasma was separated and preserved. The obtained samples were analysed using a combination of chiroptical and vibrational spectroscopies.
Results:
In a pilot study with a limited number of samples, the sensitivity of the established statistical model reached 85–90% after cross-validation. The results are better in comparison with so far the only clinically available biomarker CA-19-9.
Conclusion:
The obtained results are suitable for further testing in a larger group of patients. The spectroscopic examination of high-risk patients may form part of a screening process.
Key words:
pancreatic cancer – blood plasma – biomarkers – spectroscopy – circular dichroism – Raman optical activity – chirality
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for biomedical papers.
Submitted:
5. 11. 2015
Accepted:
30. 11. 2015
Sources
1. Trends in SEER incidence and U.S. mor-tality using the Joinpoint Regression Program, 1975– 2011 with up to five Joinpoints,1992– 2011 with up to three Joinpoints,both sexes by race/ ethnicity. [online]. Avail-able from: http:/ / seer.cancer.gov/ csr/ 1975_2011/ results_merged/ sect_22_pancreas.pdf#search=pancreatic.
2. Katz MH, Hwang R, Fleming JB et al. Tumor-node-metastasis staging of pancreatic adenocarcinoma. CA Cancer J Clin 2008; 58(2): 111– 125. doi: 10.3322/ CA.2007.0012.
3. Gobbi PG, Bergonzi M, Comelli M et al. The prognostic role of time to diagnosis and presenting symptoms in patients with pancreatic cancer. Cancer Epidemiol 2013; 37(2): 186– 190. doi: 10.1016/ j.canep.2012.12.002.
4. Dušek L, Mužík J, Kubásek M et al. Epidemiologie zhoubných nádorů v České republice. [online]. Dostupné z: www.svod.cz.
5. Gangi S, Fletcher JG, Nathan MA et al. Time interval between abnormalities seen on CT and the clinical diagnosis of pancreatic cancer: retrospective review of CT scans obtained before diagnosis. AJR Am J Roentgenol 2004; 182(4): 897– 903.
6. Bunganič B, Frič P, Zavoral M. Pancreatic adenocarcinoma – early symptoms and screening. Cas Lek Cesk 2014; 153(6): 267– 270.
7. Sah RP, Nagpal SJ, Mukhopadhyay D et al. New insights into pancreatic cancer-induced paraneoplastic diabetes. Nat Rev Gastroenterol Hepatol 2013; 10(7): 423– 433. doi: 10.1038/ nrgastro.2013.49.
8. Aggarwal G, Kamada P, Chari ST. Prevalence of diabetes mellitus in pancreatic cancer compared to common cancers. Pancreas 2013; 42(2): 198– 201. doi: 10.1097/ MPA.0b013e3182592c96.
9. Poruk KE, Firpo MA, Adler DG et al. Screening for pancreatic cancer: why, how, and who? Annal Surg 2013; 257(1): 17– 26. doi: 10.1097/ SLA.0b013e31825ffbfb.
10. Ducreux M, Cuhna AS, Caramella C. Cancer of the pancreas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015. 26 (Suppl 5): v56– v68. doi: 10.1093/ annonc/ mdv295.
11. Wang G, Lipert RJ, Jain M et al. Detection of the potential pancreatic cancer marker MUC4 in serum using surface-enhanced Raman scattering. Anal Chem 2011; 83(7): 2554– 2561. doi: 10.1021/ ac102829b.
12. Kaur S, Kumar S, Momi N et al. Mucins in pancreatic cancer and its microenvironment. Nat Rev Gastroenterol Hepatol 2013; 10(10): 607– 620. doi: 10.1038/ nrgastro.2013.120.
13. Horn A, Chakraborty S, Dey P et al. Immunocytochemistry for MUC4 and MUC16 is a useful adjunct in the diagnosis of pancreatic adenocarcinoma on fine-needle aspiration cytology. Arch Pathol Lab Med 2013; 137(4): 546– 551. doi: 10.5858/ arpa.2011-0229-OA.
14. Carrara S, Cangi MG, Arcidiacono PG et al. Mucin expression pattern in pancreatic diseases: findings from EUS-guided fine-needle aspiration biopsies. Am J Gastroenterol 2011; 106(7): 1359– 1363. doi: 10.1038/ ajg.2011.22.
15. Zhu F, Isaacs NW, Hecht L et al. Raman optical activity: a tool for protein structure analysis. Structure 2005; 13(10): 1409– 1419.
16. Barron LD, Zhu F, Hecht L et al. Raman optical activity: an incisive probe of molecular chirality and biomolecular structure. J Mol Struct 2007; 834– 836(1): 7– 16.
17. Berova N, Nakanishi K, Polavarapu PL et al. Comprehensive Chiroptical Spectroscopy. 2nd ed. New Jersey: John Wiley & Sons Inc 2012.
18. Schultz NA, Dehlendorff C, Jensen BV et al. MicroRNA biomarkers in whole blood for detection of pancreatic cancer. JAMA 2014; 311(4): 392– 404. doi: 10.1001/ jama.2013.284664.
19. Tatarkovič M, Synytsya A, Šťovíčková Let al. The minimizing of fluorescence background in Raman optical activity and Ra-man spectra of human blood plasma. Anal Bioanal Chem 2015; 407(5): 1335– 1342. doi: 10.1007/ s00216-014-8358-7.
20. Synytsya A, Judexová M, Hrubý T et al. Analysis of human blood plasma and hen egg white by chiroptical spectroscopic methods (ECD, VCD, ROA). Anal Bioanal Chem 2013; 405(16): 5441– 5453. doi: 10.1007/ s00216-013-6946-6.
21. Seufferlein T, Bachet JB, Van Cutsem E et al. Pancreatic adenocarcinoma: ESMO-ESDO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012; 23 (Suppl 7): vii33–vii 40.
22. Tempero MA, Arnoletti JP, Behrman S et al. Pancreatic adenocarcinoma. Journal Natl Compr Canc Netw 2010; 8(9): 972– 1017.
23. Withnall R, Chowdhry BZ, Silver J et al. Raman spectra of carotenoids in natural products. Spectrochim Acta, Part A 2003; 59(10): 2207– 2212.
24. Parker SF, Tavender SM, Dixon NM et al. Raman spectrum of beta-carotene using laser lines from green (514.5 nm) to near-infrared (1064 nm): implications for the characterization of conjugated polyenes. Appl Spectrosc 1999; 53(1): 86– 91.
25. Kinalwa MN, Blanch EW, Doig AJ. Accurate determination of protein secondary structure content from Raman and Raman optical activity spectra. Anal Chem 2010; 82(15): 6347– 6349. doi: 10.1021/ ac101334h.
26. Whitmore L, Wallace BA. Protein secondary structure analyses from circular dichroism spectroscopy: methods and reference databases. Biopolymers 2008; 89(5): 392– 400.
27. Hirst JD, Colella, K, Gilbert AT. Electronic circular dichroism of proteins from first -principles calculations. J Phys Chem B 2003; 107: 11813– 11819.
28. Molina V, Visa L, Conill C et al. CA 19-9 in pancreatic cancer: retrospective evaluation of patients with suspicion of pancreatic cancer. Tumour Biol 2012; 33(3): 799– 807. doi: 10.1007/ s13277-011-0297-8.
29. Kim JE, Lee KT, Lee JK et al. Clinical usefulness of carbohydrate antigen 19-9 as a screening test for pancreatic cancer in an asymptomatic population. J Gastroenterol Hepatol 2004; 19(2): 182– 186.
30. Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: an evidence-based appraisal. J Gastrointest Oncol 2012; 3(2): 105– 119. doi: 10.3978/ j.issn.2078-6891.2011.021.
31. Itzkowitz SH, Kim YS. New carbohydrate tumor markers. Gastroenterology 1986; 90(2): 491– 494.
32. Duffy MJ, Sturgeon C, Lamerz R et al. Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report. Ann Oncol 2010; 21(3): 441– 447. doi: 10.1093/ annonc/ mdp332.
33. Baine M. Pancreatic cancer biomarkers. In: Encyclopedia of Cancer. Heidelberg: Springer 2009: 790– 805.
34. Gao L, He SB, Li DC. Effects of miR-16 plus CA 19-9 detections on pancreatic cancer diagnostic performance. Clin Lab 2014; 60(1): 73– 77.
35. Rhim AD, Mirek ET, Aiello NM et al. EMT and dissemination precede pancreatic tumor formation. Cell 2012; 148(1– 2): 349– 361. doi: 10.1016/ j.cell.2011.11.025.
36. Rhim AD, Thege FI, Santana SM et al. Detection of circulating pancreas epithelial cells in patients with pancreatic cystic lesions. Gastroenterology 2014; 146(3): 647– 651. doi: 10.1053/ j.gastro.2013.12.007.
37. Apte MV, Wilson JS, Lugea A et al. A starring role for stellate cells in the pancreatic cancer microenvironment. Gastroenterology 2013; 144(6): 1210– 1219.
38. He XY, Yuan YZ. Advances in pancreatic cancer research: moving towards early detection. World J Gastroenterol 2014; 20(32): 11241– 11248. doi: 10.3748/ wjg.v20.i32.11241.
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