Inflammation: an important parameter in the search of prostate cancer biomarkers

Proteome Science

Aldo Tomasi³  Tomris Ozben¹  Giampaolo Bianchi⁴  Maria Chiara Sighinolfi⁴  Francesco Borelli⁴  Aurora Cuoghi³  Emanuela Monari³  Luca Reggiani Bonetti²  Elisa Bellei³  Stefania Bergamini³ 

[1] Department of Biochemistry, Medical Faculty, Akdeniz University, Antalya, Turkey;Section of Pathologic Anatomy, University Hospital of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy;Department of Diagnostic Medicine, Clinic and Public Health, Proteomic Lab, University Hospital of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy;Department of Urology, University Hospital of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy

关键词: 2-DE;    SELDI-ToF-MS;    Proteomics;    Prostate cancer biomarkers;    Inflammation;   

Others  :  816375
DOI  :  10.1186/1477-5956-12-32

 received in 2014-03-13, accepted in 2014-05-30,  发布年份 2014

【 摘 要 】

Background

A more specific and early diagnostics for prostate cancer (PCa) is highly desirable. In this study, being inflammation the focus of our effort, serum protein profiles were analyzed in order to investigate if this parameter could interfere with the search of discriminating proteins between PCa and benign prostatic hyperplasia (BPH).

Methods

Patients with clinical suspect of PCa and candidates for trans-rectal ultrasound guided prostate biopsy (TRUS) were enrolled. Histological specimens were examined in order to grade and classify the tumor, identify BPH and detect inflammation. Surface Enhanced Laser Desorption/Ionization-Time of Flight-Mass Spectrometry (SELDI-ToF-MS) and two-dimensional gel electrophoresis (2-DE) coupled with Liquid Chromatography-MS/MS (LC-MS/MS) were used to analyze immuno-depleted serum samples from patients with PCa and BPH.

Results

The comparison between PCa (with and without inflammation) and BPH (with and without inflammation) serum samples by SELDI-ToF-MS analysis did not show differences in protein expression, while changes were only observed when the concomitant presence of inflammation was taken into consideration. In fact, when samples with histological sign of inflammation were excluded, 20 significantly different protein peaks were detected. Subsequent comparisons (PCa with inflammation vs PCa without inflammation, and BPH with inflammation vs BPH without inflammation) showed that 16 proteins appeared to be modified in the presence of inflammation, while 4 protein peaks were not modified. With 2-DE analysis, comparing PCa without inflammation vs PCa with inflammation, and BPH without inflammation vs the same condition in the presence of inflammation, were identified 29 and 25 differentially expressed protein spots, respectively. Excluding samples with inflammation the comparison between PCa vs BPH showed 9 unique PCa proteins, 4 of which overlapped with those previously identified in the presence of inflammation, while other 2 were new proteins, not identified in our previous comparisons.

Conclusions

The present study indicates that inflammation might be a confounding parameter during the proteomic research of candidate biomarkers of PCa. These results indicate that some possible biomarker-candidate proteins are strongly influenced by the presence of inflammation, hence only a well-selected protein pattern should be considered for potential marker of PCa.

【 授权许可】

   
2014 Bergamini et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Larkin SE, Zeidan B, Taylor MG, Bickers B, Al-Ruwaili J, Aukim-Hastie C, Townsend PA: Proteomics in prostate cancer biomarker discovery. Expert Rev Proteomics 2010, 7:93-102.
• [2]You J, Cozzi P, Walsh B, Willcox M, Kearsley J, Russell P, Li Y: Innovative biomarkers for prostate cancer early diagnosis and progression. Crit Rev Oncol Hematol 2010, 73:10-22.
• [3]Al-Ruwaili JA, Larkin SET, Zeidan BA, Taylor MG, Adra CN, Aukim-Hastie CL, Townsend PA: Discovery of serum protein biomarkers for prostate cancer progression by proteomic analysis. Cancer Genomics Proteomics 2010, 7:93-103.
• [4]Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA Cancer J Clin 2009, 59:225-249.
• [5]Beduschi MC, Oesterling JE: Percent free prostate-specific antigen: the next frontier in prostate-specific antigen testing. Urology 1998, 51:98-109.
• [6]Klein LT, Lowe FC: The effects of prostatic manipulation on prostate-specific-antigen levels. Urol Clin North Am 1997, 24:293-297.
• [7]McLerran D, Grizzle WE, Feng Z, Bigbee WL, Banez LL, Cazares LH, Chan DW, Diaz J, Izbicka E, Kagan J, Malehorn DE, Malik G, Oelschlager D, Partin A, Randolph T, Rosenzweig N, Srivastava S, Srivastava S, Thompson IM, Thornquist M, Troyer D, Yasui Y, Zhang Z, Zhu L, Semmes OJ: Analytical validation of serum proteomic profiling for diagnosis of prostate cancer: sources of sample bias. Clin Chem 2008, 54:44-52.
• [8]Qu Y, Adam BL, Yasui Y, Ward MD, Cazares LH, Schellhammer PF, Feng Z, Semmes OJ, Wright GL Jr: Boosted decision tree analysis of surface-enhanced laser desorption/ionization mass specral serum profiles discriminates prostate cancer from noncancer patients. Clin Chem 2002, 48:1835-1843.
• [9]Goo YA, Goodlett DR: Advances in proteomic cancer biomarker discovery. J Proteomics 2010, 73:1839-1850.
• [10]Lin JF, Xu J, Tian HY, Gao X, Chen QX, Gu Q, Xu GJ, Song JD, Zhao FK: Identification of candidate prostate cancer biomarkers in prostate needle biopsy specimens using proteomic analysis. Int J Cancer 2007, 121:2596-2605.
• [11]Alaiya A, Roblick U, Egevad L, Carlsson A, Franzén B, Volz D, Huwendiek S, Linder S, Auer G: Polypeptide expression in prostate hyperplasia and prostate adenocarcinoma. Anal Cell Pathol 2000, 21:1-9.
• [12]Cazares LH, Adam BL, Ward MD, Nasim S, Schellhammer PF, Semmes OJ, Wright GL Jr: Normal, bening, preneoplastic, and malignant prostate cells have distinct protein expression profiles resolved by surface enhanced laser desorption/ionization mass spectrometry. Clin Cancer Res 2002, 8:2541-2552.
• [13]Reed AB, Parekh DJ: Biomarkers for prostate cancer detection. Expert Rev Anticancer Ther 2010, 10:103-114.
• [14]Parekh DJ, Ankerst DP, Troyer D, Srivastava S, Thompson IM: Biomarkers for prostate cancer detection. J Urol 2007, 178:2252-2259.
• [15]Adam BL, Qu Y, Davis JW, Ward MD, Clements MA, Cazares LH, Semmes OJ, Schellhammer PF, Yasui Y, Feng Z, Wright GL Jr: Serum protein fingerprinting coupled with a pattern-matching algorithm distinguishes prostate cancer from benign prostate hyperplasia and healthy men. Cancer Res 2002, 62:3609-3614.
• [16]Ornstein DK, Rayford W, Fusaro VA, Conrads TP, Ross SJ, Hitt BA, Wiggins WW, Veenstra TD, Liotta LA, Petricoin EF 3rd: Serum proteomic profiling can discriminate prostate cancer from benign prostates in men with total prostate specific antigen levels between 2.5 and 15.0 ng/ml. J Urol 2004, 172:1302-1305.
• [17]Ummanni R, Junker H, Zimmermann U, Venz S, Teller S, Giebel J, Scharf C, Woenckhaus C, Dombrowski F, Walther R: Prohibitin identified by proteomic analysis of prostate biopsies distinguishes hyperplasia and cancer. Cancer Lett 2008, 266:171-185.
• [18]Wang W, Bergh A, Damber JE: Morphological transition of proliferative inflammatory atrophy to high grade intraepithelial neoplasia and cancer in human prostate. Prostate 2009, 69:1378-1386.
• [19]Abdel-Muguid TA, Mosli HA, Al-Maghrabi JA: Prostate inflammation. Association with benign prostatic hyperplasia and prostate cancer. Saudi Med J 2009, 30:1563-1567.
• [20]Mosli HA, Abdel-Meguid TA, Al-Maghrabi JA, Kamal WK, Saadah HA, Farsi HM: The clinicopathologic patterns of prostatic diseases and prostate cancer in Saudi patients. Saudi Med J 2009, 30:1439-1443.
• [21]Mantovani A, Allavena P, Sica A, Balkwill F: Cancer-related inflammation. Nature 2008, 454:436-444.
• [22]Byrne JC, Downes MR, O’Donoghue N, O’Keane C, O’Neill A, Fan Y, Fitzpatrick JM, Dunn M, Watson RW: 2D-DIGE as a strategy to identify serum markers for the progression of prostate cancer. J Proteome Res 2009, 8:942-957.
• [23]Bellei E, Bergamini S, Monari E, Fantoni LI, Cuoghi A, Ozben T, Tomasi A: High-abundance proteins depletion for serum proteomic analysis: concomitant removal of non-targeted proteins. Amino Acids 2011, 40:145-156.
• [24]Pace G, Di Massimo C, De Amicis D, Vicentini C, Tozzi Ciancarelli MG: Inflammation and endothelial activation in benign prostatic hyperplasia and prostate cancer. Int Braz J Urol 2011, 37:617-622.
• [25]Chechlinska M, Kowalewska M, Nowak R: Systemic inflammation as a confounding factor in cancer biomarker discovery and validation. Nature Rev 2010, 10:2-3.
• [26]Balkwill F, Mantovani A: Inflammation and cancer: back to Virchow? Lancet 2001, 357:539-545.
• [27]Liu C: Serum Amyloid A protein in clinical cancer diagnosis. Pathol Oncol Res 2012, 18:117-121.
• [28]Menschikowski M, Hagelgans A, Fuessel S, Mareninova OA: Serum Amyloid A, phospholipase A2-IIA and C-reactive protein as inflammatory biomarkers for prostate diseases. Inflamm Res 2013, 62(12):1063-1072.
• [29]Tolosano E, Altruda S: Hemopexin: structure, function, and regulation. DNA Cell Biol 2002, 21(4):297-306.
• [30]Debruyne EN, Vanderschaeghe D, Van Vlierberghe H, Vanhecke A, Callewaert N, Delanghe JR: Diagnostic value of the hemopexin N-glycan profile in hepatocellular carcinoma patients. Clin Chem 2010, 56(5):823-831.
• [31]O’Reilly MS: Antiangiogenic antithrombin. Semin Thromb Hemost 2007, 33(7):660-666.
• [32]Cao Y, Lundwall A, Gadaleanu V, Lilja H, Bjartell A: Anti-thrombin is expressed in the benign prostatic epithelium and in prostate cancer and is capable of forming complexex with prostate-specific antigen and human glandular kallikrein 2. Am J Pathol 2002, 161:2053-2063.
• [33]Honegger H, Anderson N, Hewitt LA, Tullis JL: Antithrombin III profiles in malignancy, relationship primary tumors and metastatic sites. Thromb Haemost 1981, 46(2):500-503.
• [34]Hong SK, Ko DW, Park J, Kim IS, Doo SH, Yoon CY, Park H, Lee WK, Kim DS, Jeong SJ, Byun SS, Lee SE: Alteration of antithrombin III and D-dimer levels in clinically localized prostate cancer. Korean J Urol 2010, 51:25-29.
• [35]Edge S, Byrd DR, Compton CC, Fritz AG, Green FL: AJCG Cancer Staging Handbook. In AJCC Cancer Staging Manual. 7th edition. New York: Springer-Verlag; 2010:525-538.
• [36]Epstein JI: An update of the Gleason Grading System. J Urol 2010, 183:433-440.
• [37]Monari E, Casali C, Cuoghi A, Nesci J, Bellei E, Bergamini S, Fantoni LI, Natali P, Morandi U, Tomasi A: Enriched sera protein profiling for detection of non-small cell lung cancer biomarkers. Proteome Sci 2011, 9:55. BioMed Central Full Text
• [38]Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976, 72:248.
• [39]Bellei E, Rossi E, Lucchi L, Uggeri S, Albertazzi A, Tomasi A, Iannone A: Proteomic analysis of early urinary biomarkers of renal changes in type 2 diabetic patients. Proteomics Clin Appl 2008, 2:478-491.