Skip to main content
Top
Published in: World Journal of Surgical Oncology 1/2013

Open Access 01-12-2013 | Research

Proteomic analysis of non-small cell lung cancer tissue interstitial fluids

Authors: Shaomin Li, Rui Wang, Mingxin Zhang, Lina Wang, Shaoli Cheng

Published in: World Journal of Surgical Oncology | Issue 1/2013

Login to get access

Abstract

Background

Non-small cell lung cancer (NSCLC) accounts for more than 80% of all lung cancers, and reliable biomarkers are desirable. The present investigation assesses our ability to identify tumor relevant proteins from NSCLC tissue interstitial fluid (TIF).

Methods

Paired TIF was collected from three NSCLC patients at the time of surgery, and resolved by two-dimensional gel electrophoresis and in-gel digestion for proteomic analysis. Differentially expressed spots were extracted from the two-dimensional gel and characterized by high-performance liquid chromatography-tandem mass spectrometry. Then, ELISA was used to verify the expression of peroxiredoxin 1 (PRDX1) in TIF of patients with NSCLC and benign lung disease. Finally, the relationship between expression of PRDX1 and clinicopathological features was determined.

Results

Comparative proteomic analysis showed 24 protein spots were differentially expressed with significant changes, including 11 upregulated proteins and 13 downregulated proteins. Of these, PRDX1 was selected for validation in TIF by Western blot and expression of PRDX1 was confirmed to be upregulated in tumor TIF. It was also demonstrated that PRDX1 was significantly elevated in 40 NSCLC patients with a mean level of 36.0 ng/mL compared to 6.26 ng/mL from 20 patients with benign lung disease. A significant correlation was found between the high level of PRDX1 expression and lymph node metastasis and tumor differentiation.

Conclusions

PRDX1 might be correlated with lymph node metastasis and differentiation, and its elevated expression in TIF may be an adverse biomarker for patients with NSCLC. PRDX1 may be attributed to the malignant transformation of NSCLC, and attention should be paid to a possible target for therapy.
Appendix
Available only for authorised users
Literature
1.
go back to reference Alberg AJ, Ford JG, Samet JM, American College of Chest Physicians: Epidemiology of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest. 2007, 132: 29S-55S. 10.1378/chest.07-1347.CrossRefPubMed Alberg AJ, Ford JG, Samet JM, American College of Chest Physicians: Epidemiology of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest. 2007, 132: 29S-55S. 10.1378/chest.07-1347.CrossRefPubMed
2.
go back to reference Mirshahidi HR, Hsueh CT: Updates in non-small cell lung cancer–insights from the 2009 45th annual meeting of the American society of clinical oncology. J Hematol Oncol. 2010, 3: 18. 10.1186/1756-8722-3-18.PubMedCentralCrossRefPubMed Mirshahidi HR, Hsueh CT: Updates in non-small cell lung cancer–insights from the 2009 45th annual meeting of the American society of clinical oncology. J Hematol Oncol. 2010, 3: 18. 10.1186/1756-8722-3-18.PubMedCentralCrossRefPubMed
3.
go back to reference Singhal S, Vachani A, Antin-Ozerkis D, Kaiser LR, Albelda SM: Prognostic implications of cell cycle, apoptosis, and angiogenesis biomarkers in non-small cell lung cancer: a review. Clin Cancer Res. 2005, 11: 3974-3986. 10.1158/1078-0432.CCR-04-2661.CrossRefPubMed Singhal S, Vachani A, Antin-Ozerkis D, Kaiser LR, Albelda SM: Prognostic implications of cell cycle, apoptosis, and angiogenesis biomarkers in non-small cell lung cancer: a review. Clin Cancer Res. 2005, 11: 3974-3986. 10.1158/1078-0432.CCR-04-2661.CrossRefPubMed
4.
go back to reference Teng PN, Hood BL, Sun M, Dhir R, Conrads TP: Differential proteomic analysis of renal cell carcinoma tissue interstitial fluid. J Proteome Res. 2011, 10: 1333-1342. 10.1021/pr101074p.CrossRefPubMed Teng PN, Hood BL, Sun M, Dhir R, Conrads TP: Differential proteomic analysis of renal cell carcinoma tissue interstitial fluid. J Proteome Res. 2011, 10: 1333-1342. 10.1021/pr101074p.CrossRefPubMed
5.
go back to reference Baronzio G, Freitas I, Kwaan HC: Tumor microenvironment and hemorheological abnormalities. Semin Thromb Hemost. 2003, 29: 489-497.CrossRefPubMed Baronzio G, Freitas I, Kwaan HC: Tumor microenvironment and hemorheological abnormalities. Semin Thromb Hemost. 2003, 29: 489-497.CrossRefPubMed
6.
go back to reference Celis JE, Gromov P, Cabezón T, Moreira JM, Ambartsumian N, Sandelin K, Rank F, Gromova I: Proteomic characterization of the interstitial fluid perfusing the breast tumor microenvironment: a novel resource for biomarker and therapeutic target discovery. Mol Cell Proteomics. 2004, 3: 327-344. 10.1074/mcp.M400009-MCP200.CrossRefPubMed Celis JE, Gromov P, Cabezón T, Moreira JM, Ambartsumian N, Sandelin K, Rank F, Gromova I: Proteomic characterization of the interstitial fluid perfusing the breast tumor microenvironment: a novel resource for biomarker and therapeutic target discovery. Mol Cell Proteomics. 2004, 3: 327-344. 10.1074/mcp.M400009-MCP200.CrossRefPubMed
7.
go back to reference Andon NL, Hollingworth S, Koller A, Greenland AJ, Yates JR, Haynes PA: Proteomic characterization of wheat amyloplasts using identification of proteins by tandem mass spectrometry. Proteomics. 2002, 2: 1156-1168. 10.1002/1615-9861(200209)2:9<1156::AID-PROT1156>3.0.CO;2-4.CrossRefPubMed Andon NL, Hollingworth S, Koller A, Greenland AJ, Yates JR, Haynes PA: Proteomic characterization of wheat amyloplasts using identification of proteins by tandem mass spectrometry. Proteomics. 2002, 2: 1156-1168. 10.1002/1615-9861(200209)2:9<1156::AID-PROT1156>3.0.CO;2-4.CrossRefPubMed
8.
go back to reference Yates JR, Eng JK, McCormack AL, Schieltz D: Method to correlate tandem mass spectra of modified peptides to amino acid sequences in the protein database. Anal Chem. 1995, 67: 1426-1436. 10.1021/ac00104a020.CrossRefPubMed Yates JR, Eng JK, McCormack AL, Schieltz D: Method to correlate tandem mass spectra of modified peptides to amino acid sequences in the protein database. Anal Chem. 1995, 67: 1426-1436. 10.1021/ac00104a020.CrossRefPubMed
9.
go back to reference Yang Y, Liu X, Fang X, Wang X: Proteomic analysis of mitochondria in Raji cells following exposure to radiation: implications for radiotherapy response. Protein Pept Lett. 2009, 16: 1350-1359. 10.2174/092986609789353646.CrossRef Yang Y, Liu X, Fang X, Wang X: Proteomic analysis of mitochondria in Raji cells following exposure to radiation: implications for radiotherapy response. Protein Pept Lett. 2009, 16: 1350-1359. 10.2174/092986609789353646.CrossRef
10.
go back to reference Gromov P, Gromova I, Bunkenborg J, Cabezon T, Moreira JM, Timmermans-Wielenga V, Roepstorff P, Rank F, Celis JE: Up-regulated proteins in the fluid bathing the tumour cell microenvironment as potential serological markers for early detection of cancer of the breast. Mol Oncol. 2010, 4: 65-89. 10.1016/j.molonc.2009.11.003.CrossRefPubMed Gromov P, Gromova I, Bunkenborg J, Cabezon T, Moreira JM, Timmermans-Wielenga V, Roepstorff P, Rank F, Celis JE: Up-regulated proteins in the fluid bathing the tumour cell microenvironment as potential serological markers for early detection of cancer of the breast. Mol Oncol. 2010, 4: 65-89. 10.1016/j.molonc.2009.11.003.CrossRefPubMed
11.
go back to reference Stone MD, Odland RM, McGowan T, Onsongo G, Tang C, Rhodus NL, Jagtap P, Bandhakavi S, Griffin TJ: Novel in situ collection of tumor interstitial fluid from a head and neck squamous carcinoma reveals a unique proteome with diagnostic potential. Clin Proteomics. 2010, 6: 75-82. 10.1007/s12014-010-9050-3.PubMedCentralCrossRefPubMed Stone MD, Odland RM, McGowan T, Onsongo G, Tang C, Rhodus NL, Jagtap P, Bandhakavi S, Griffin TJ: Novel in situ collection of tumor interstitial fluid from a head and neck squamous carcinoma reveals a unique proteome with diagnostic potential. Clin Proteomics. 2010, 6: 75-82. 10.1007/s12014-010-9050-3.PubMedCentralCrossRefPubMed
12.
go back to reference Hoskins ER, Hood BL, Sun M, Krivak TC, Edwards RP, Conrads TP: Proteomic analysis of ovarian cancer proximal fluids: validation of elevated peroxiredoxin 1 in patient peripheral circulation. PLoS One. 2011, 6: e25056. 10.1371/journal.pone.0025056.PubMedCentralCrossRefPubMed Hoskins ER, Hood BL, Sun M, Krivak TC, Edwards RP, Conrads TP: Proteomic analysis of ovarian cancer proximal fluids: validation of elevated peroxiredoxin 1 in patient peripheral circulation. PLoS One. 2011, 6: e25056. 10.1371/journal.pone.0025056.PubMedCentralCrossRefPubMed
13.
go back to reference Peebles KA, Duncan MW, Ruch RJ, Malkinson AM: Proteomic analysis of a neoplastic mouse lung epithelial cell line whose tumorigenicity has been abrogated by transfection with the gap junction structural gene for connexin 43, Gja1. Carcinogenesis. 2003, 24: 651-657. 10.1093/carcin/bgg008.CrossRefPubMed Peebles KA, Duncan MW, Ruch RJ, Malkinson AM: Proteomic analysis of a neoplastic mouse lung epithelial cell line whose tumorigenicity has been abrogated by transfection with the gap junction structural gene for connexin 43, Gja1. Carcinogenesis. 2003, 24: 651-657. 10.1093/carcin/bgg008.CrossRefPubMed
14.
go back to reference Zhang L, Cilley RE, Chinoy MR: Suppression subtractive hybridization to identify gene expressions in variant and classic small cell lung cancer cell lines. Surg Res. 2000, 93: 108-119. 10.1006/jsre.2000.5957.CrossRef Zhang L, Cilley RE, Chinoy MR: Suppression subtractive hybridization to identify gene expressions in variant and classic small cell lung cancer cell lines. Surg Res. 2000, 93: 108-119. 10.1006/jsre.2000.5957.CrossRef
15.
go back to reference Wu W, Tang X, Hu W, Lotan R, Hong WK, Mao L: Identification and validation of metastasis-associated proteins in head and neck cancer cell lines by two-dimensional electrophoresis and mass spectrometry. Clin Exp Metastasis. 2002, 19: 319-326. 10.1023/A:1015515119300.CrossRefPubMed Wu W, Tang X, Hu W, Lotan R, Hong WK, Mao L: Identification and validation of metastasis-associated proteins in head and neck cancer cell lines by two-dimensional electrophoresis and mass spectrometry. Clin Exp Metastasis. 2002, 19: 319-326. 10.1023/A:1015515119300.CrossRefPubMed
16.
go back to reference He P, Naka T, Serada S, Fujimoto M, Tanaka T, Hashimoto S, Shima Y, Yamadori T, Suzuki H, Hirashima T, Matsui K, Shiono H, Okumura M, Nishida T, Tachibana I, Norioka N, Norioka S, Kawase I: Proteomics-based identification of alpha-enolase as a tumor antigen in non-small lung cancer. Cancer Sci. 2007, 98: 1234-1240. 10.1111/j.1349-7006.2007.00509.x.CrossRefPubMed He P, Naka T, Serada S, Fujimoto M, Tanaka T, Hashimoto S, Shima Y, Yamadori T, Suzuki H, Hirashima T, Matsui K, Shiono H, Okumura M, Nishida T, Tachibana I, Norioka N, Norioka S, Kawase I: Proteomics-based identification of alpha-enolase as a tumor antigen in non-small lung cancer. Cancer Sci. 2007, 98: 1234-1240. 10.1111/j.1349-7006.2007.00509.x.CrossRefPubMed
17.
go back to reference Chang GC, Liu KJ, Hsieh CL, Hu TS, Charoenfuprasert S, Liu HK, Luh KT, Hsu LH, Wu CW, Ting CC, Chen CY, Chen KC, Yang TY, Chou TY, Wang WH, Whang-Peng J, Shih NY: Identification of alpha-enolase as an autoantigen in lung cancer: its overexpression is associated with clinical outcomes. Clin Cancer Res. 2006, 12: 5746-5754. 10.1158/1078-0432.CCR-06-0324.CrossRefPubMed Chang GC, Liu KJ, Hsieh CL, Hu TS, Charoenfuprasert S, Liu HK, Luh KT, Hsu LH, Wu CW, Ting CC, Chen CY, Chen KC, Yang TY, Chou TY, Wang WH, Whang-Peng J, Shih NY: Identification of alpha-enolase as an autoantigen in lung cancer: its overexpression is associated with clinical outcomes. Clin Cancer Res. 2006, 12: 5746-5754. 10.1158/1078-0432.CCR-06-0324.CrossRefPubMed
18.
go back to reference Tew KD, Manevich Y, Grek C, Xiong Y, Uys J, Townsend DM: The role of glutathione S-transferase P in signaling pathways and S-glutathionylation in cancer. Free Radic Biol Med. 2011, 51: 299-313. 10.1016/j.freeradbiomed.2011.04.013.PubMedCentralCrossRefPubMed Tew KD, Manevich Y, Grek C, Xiong Y, Uys J, Townsend DM: The role of glutathione S-transferase P in signaling pathways and S-glutathionylation in cancer. Free Radic Biol Med. 2011, 51: 299-313. 10.1016/j.freeradbiomed.2011.04.013.PubMedCentralCrossRefPubMed
19.
go back to reference Nyström T, Yang J, Molin M: Peroxiredoxins, gerontogenes linking aging to genome instability and cancer. Genes Dev. 2012, 26: 2001-2008. 10.1101/gad.200006.112.PubMedCentralCrossRefPubMed Nyström T, Yang J, Molin M: Peroxiredoxins, gerontogenes linking aging to genome instability and cancer. Genes Dev. 2012, 26: 2001-2008. 10.1101/gad.200006.112.PubMedCentralCrossRefPubMed
20.
go back to reference Riddell JR, Bshara W, Moser MT, Spernyak JA, Foster BA, Gollnick SO: Peroxiredoxin 1 controls prostate cancer growth through Toll-like receptor 4-dependent regulation of tumor vasculature. Cancer Res. 2011, 71: 1637-1646. 10.1158/0008-5472.CAN-10-3674.PubMedCentralCrossRefPubMed Riddell JR, Bshara W, Moser MT, Spernyak JA, Foster BA, Gollnick SO: Peroxiredoxin 1 controls prostate cancer growth through Toll-like receptor 4-dependent regulation of tumor vasculature. Cancer Res. 2011, 71: 1637-1646. 10.1158/0008-5472.CAN-10-3674.PubMedCentralCrossRefPubMed
21.
go back to reference Wang X, He S, Sun JM, Delcuve GP, Davie JR: Selective association of peroxiredoxin 1 with genomic DNA and COX-2 upstream promoter elements in estrogen receptor negative breast cancer cells. Mol Biol Cell. 2010, 21: 2987-2995. 10.1091/mbc.E10-02-0160.PubMedCentralCrossRefPubMed Wang X, He S, Sun JM, Delcuve GP, Davie JR: Selective association of peroxiredoxin 1 with genomic DNA and COX-2 upstream promoter elements in estrogen receptor negative breast cancer cells. Mol Biol Cell. 2010, 21: 2987-2995. 10.1091/mbc.E10-02-0160.PubMedCentralCrossRefPubMed
22.
go back to reference Wu XY, Fu ZX, Wang XH: Peroxiredoxins in colorectal neoplasms. Histol Histopathol. 2010, 25: 1297-1303.PubMed Wu XY, Fu ZX, Wang XH: Peroxiredoxins in colorectal neoplasms. Histol Histopathol. 2010, 25: 1297-1303.PubMed
23.
go back to reference Chang JW, Lee SH, Jeong JY, Chae HZ, Kim YC, Park ZY, Yoo YJ: Peroxiredoxin-I is an autoimmunogenic tumor antigen in non-small cell lung cancer. FEBS Lett. 2005, 579: 2873-2877. 10.1016/j.febslet.2005.04.028.CrossRefPubMed Chang JW, Lee SH, Jeong JY, Chae HZ, Kim YC, Park ZY, Yoo YJ: Peroxiredoxin-I is an autoimmunogenic tumor antigen in non-small cell lung cancer. FEBS Lett. 2005, 579: 2873-2877. 10.1016/j.febslet.2005.04.028.CrossRefPubMed
24.
go back to reference Kim JH, Bogner PN, Ramnath N, Park Y, Yu J, Park YM: Elevated peroxiredoxin 1, but not NF-E2-related factor 2, is an independent prognostic factor for disease recurrence and reduced survival in stage I non-small cell lung cancer. Clin Cancer Res. 2007, 13: 3875-3882. 10.1158/1078-0432.CCR-06-2893.CrossRefPubMed Kim JH, Bogner PN, Ramnath N, Park Y, Yu J, Park YM: Elevated peroxiredoxin 1, but not NF-E2-related factor 2, is an independent prognostic factor for disease recurrence and reduced survival in stage I non-small cell lung cancer. Clin Cancer Res. 2007, 13: 3875-3882. 10.1158/1078-0432.CCR-06-2893.CrossRefPubMed
25.
go back to reference Kim JH, Bogner PN, Baek SH, Ramnath N, Liang P, Kim HR, Andrews C, Park YM: Up-regulation of peroxiredoxin 1 in lung cancer and its implication as a prognostic and therapeutic target. Clin Cancer Res. 2008, 14: 2326-2333. 10.1158/1078-0432.CCR-07-4457.CrossRefPubMed Kim JH, Bogner PN, Baek SH, Ramnath N, Liang P, Kim HR, Andrews C, Park YM: Up-regulation of peroxiredoxin 1 in lung cancer and its implication as a prognostic and therapeutic target. Clin Cancer Res. 2008, 14: 2326-2333. 10.1158/1078-0432.CCR-07-4457.CrossRefPubMed
26.
go back to reference Ho JN, Lee SB, Lee SS, Yoon SH, Kang GY, Hwang SG, Um HD: Phospholipase A2 activity of peroxiredoxin 6 promotes invasion and metastasis of lung cancer cells. Mol Cancer Ther. 2010, 9: 825-832. 10.1158/1535-7163.MCT-09-0904.CrossRefPubMed Ho JN, Lee SB, Lee SS, Yoon SH, Kang GY, Hwang SG, Um HD: Phospholipase A2 activity of peroxiredoxin 6 promotes invasion and metastasis of lung cancer cells. Mol Cancer Ther. 2010, 9: 825-832. 10.1158/1535-7163.MCT-09-0904.CrossRefPubMed
27.
go back to reference Kim YS, Lee HL, Lee KB, Park JH, Chung WY, Lee KS, Sheen SS, Park KJ, Hwang SC: Nuclear factor E2-related factor 2 dependent overexpression of sulfiredoxin and peroxiredoxin III in human lung cancer. Korean J Intern Med. 2011, 26: 304-313.PubMedCentralCrossRefPubMed Kim YS, Lee HL, Lee KB, Park JH, Chung WY, Lee KS, Sheen SS, Park KJ, Hwang SC: Nuclear factor E2-related factor 2 dependent overexpression of sulfiredoxin and peroxiredoxin III in human lung cancer. Korean J Intern Med. 2011, 26: 304-313.PubMedCentralCrossRefPubMed
28.
go back to reference Wei Q, Jiang H, Xiao Z, Baker A, Young MR, Veenstra TD, Colburn NH: Sulfiredoxin-peroxiredoxin IV axis promotes human lung cancer progression through modulation of specific phosphokinase signaling. Proc Natl Acad Sci U S A. 2011, 108: 7004-7009. 10.1073/pnas.1013012108.PubMedCentralCrossRefPubMed Wei Q, Jiang H, Xiao Z, Baker A, Young MR, Veenstra TD, Colburn NH: Sulfiredoxin-peroxiredoxin IV axis promotes human lung cancer progression through modulation of specific phosphokinase signaling. Proc Natl Acad Sci U S A. 2011, 108: 7004-7009. 10.1073/pnas.1013012108.PubMedCentralCrossRefPubMed
Metadata
Title
Proteomic analysis of non-small cell lung cancer tissue interstitial fluids
Authors
Shaomin Li
Rui Wang
Mingxin Zhang
Lina Wang
Shaoli Cheng
Publication date
01-12-2013
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2013
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/1477-7819-11-173

Other articles of this Issue 1/2013

World Journal of Surgical Oncology 1/2013 Go to the issue