期刊论文详细信息
World Journal of Surgical Oncology
Proteomic analysis of non-small cell lung cancer tissue interstitial fluids
Shaoli Cheng1  Lina Wang2  Mingxin Zhang4  Rui Wang3  Shaomin Li5 
[1] Morphological Experiment Centre, Medicine School, Xi’an Jiaotong University, Xia’an, Shaanxi Province 710061, China;Department of Emergency, Second Affiliated Hospital, Medical School, Xi’an Jiaotong University, Xi’an, Shaanxi Province 710004, China;Department of Respiratory Medicine, Xi’an Central Hospital, Xi’an, Shaanxi Province 710003, China;Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi Province 710038, China;Department of Thoracic Surgery, Second Affiliated Hospital, Medical School, Xi’an Jiaotong University, Xi’an, Shaanxi Province 710004, China
关键词: Peroxiredoxin 1;    Tissue interstitial fluid;    Non-small cell lung cancer;    Proteomic;   
Others  :  823591
DOI  :  10.1186/1477-7819-11-173
 received in 2013-03-26, accepted in 2013-07-26,  发布年份 2013
PDF
【 摘 要 】

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.

【 授权许可】

   
2013 Li et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140713011001977.pdf 2026KB PDF download
Figure 5. 9KB Image download
Figure 4. 11KB Image download
Figure 3. 19KB Image download
Figure 2. 19KB Image download
Figure 1. 70KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】
  • [1]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.
  • [2]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. BioMed Central Full Text
  • [3]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.
  • [4]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.
  • [5]Baronzio G, Freitas I, Kwaan HC: Tumor microenvironment and hemorheological abnormalities. Semin Thromb Hemost 2003, 29:489-497.
  • [6]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.
  • [7]Andon NL, Hollingworth S, Koller A, Greenland AJ, Yates JR 3rd, Haynes PA: Proteomic characterization of wheat amyloplasts using identification of proteins by tandem mass spectrometry. Proteomics 2002, 2:1156-1168.
  • [8]Yates JR 3rd, 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.
  • [9]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]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.
  • [11]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.
  • [12]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.
  • [13]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.
  • [14]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.
  • [15]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.
  • [16]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.
  • [17]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.
  • [18]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.
  • [19]Nyström T, Yang J, Molin M: Peroxiredoxins, gerontogenes linking aging to genome instability and cancer. Genes Dev 2012, 26:2001-2008.
  • [20]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.
  • [21]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.
  • [22]Wu XY, Fu ZX, Wang XH: Peroxiredoxins in colorectal neoplasms. Histol Histopathol 2010, 25:1297-1303.
  • [23]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.
  • [24]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.
  • [25]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.
  • [26]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.
  • [27]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.
  • [28]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.
  文献评价指标  
  下载次数:12次 浏览次数:3次