Proteomic profiling of osteosarcoma cells identifies ALDOA and SULT1A3 as negative survival markers of human osteosarcoma

Osteosarcoma (OSA) is the most common primary malignancy of bone. Molecular mechanism underlying OSA remains to be fully elucidated. It is critical to identify reliable diagnostic and prognostic markers for OSA at the molecular levels. This study is designed to investigate possible molecular mechanisms behind OSA development and to identify novel prognostic markers related to OSA survival. We conduct a comprehensive proteomic profiling analysis of human OSA cell lines with differential metastatic potential. Through comprehensive combinatorial analyses of the proteomic data and the previously obtained cDNA microarray results, we identify 37 candidate proteins which are differentially expressed in OSA sublines. Among them, ALDOA and SULT1A3 are selected for further investigation. The expressions of protein are confirmed by Western blotting analysis. We further analyze the expression levels of ALDOA and SULT1A3 from 40 clinical cases of OSA. The results demonstrate that the expression of ALDOA and/or SULT1A3 is significantly higher in patients with worse survival time than patients with better survival time. Five‐year survival analysis shows there is a statistically significant difference between two patient populations. The data strongly suggest that ALDOA and/or SULT1A3 expression level in biopsy samples may predict the clinical outcomes of OSA patients. Furthermore, the biological functions of ALDOA and SULT1A3 may be implicated in OSA development and/or progression. © 2012 Wiley Periodicals, Inc.

[1]  R. Schneider,et al.  Microvilli expressed on glioma cells keep cytotoxic cells at a distance , 2011, Cancer biology & therapy.

[2]  Andy J. Minn,et al.  Genes that mediate breast cancer metastasis to lung , 2005, Nature.

[3]  Rainer Cramer,et al.  Evaluation of Two-dimensional Differential Gel Electrophoresis for Proteomic Expression Analysis of a Model Breast Cancer Cell System* , 2002, Molecular & Cellular Proteomics.

[4]  S. Gygi,et al.  Correlation between Protein and mRNA Abundance in Yeast , 1999, Molecular and Cellular Biology.

[5]  S. Ong,et al.  An evaluation of the use of two-dimensional gel electrophoresis in proteomics. , 2001, Biomolecular engineering.

[6]  J. Luk,et al.  Proteomic profiling of hepatocellular carcinoma in Chinese cohort reveals heat‐shock proteins (Hsp27, Hsp70, GRP78) up‐regulation and their associated prognostic values , 2006, Proteomics.

[7]  N. Anderson,et al.  Proteome and proteomics: New technologies, new concepts, and new words , 1998, Electrophoresis.

[8]  F. Liu,et al.  Proteomic analysis of a highly metastatic gastric cancer cell line using two-dimensional differential gel electrophoresis. , 2006, Oncology reports.

[9]  P. Laird,et al.  CpG island hypermethylation in human colorectal tumors is not associated with DNA methyltransferase overexpression. , 1999, Cancer research.

[10]  O. Warburg [Origin of cancer cells]. , 1956, Oncologia.

[11]  X. Qiu,et al.  Gene expression profiles of human osteosarcoma cell sublines with different pulmonary metastatic potentials , 2011, Cancer biology & therapy.

[12]  Eric S. Lander,et al.  Genomic analysis of metastasis reveals an essential role for RhoC , 2000, Nature.

[13]  Yao-Tseng Chen,et al.  Human lung cancer antigens recognized by autologous antibodies: definition of a novel cDNA derived from the tumor suppressor gene locus on chromosome 3p21.3. , 1998, Cancer research.

[14]  T. Ørntoft,et al.  Gene expression profiling: monitoring transcription and translation products using DNA microarrays and proteomics , 2000, FEBS letters.

[15]  Yi-yong Wu,et al.  On the sulfation and methylation of catecholestrogens in human mammary epithelial cells and breast cancer cells. , 2008, Biological & pharmaceutical bulletin.

[16]  H. Tsuchiya,et al.  Effect of timing of pulmonary metastases identification on prognosis of patients with osteosarcoma: the Japanese Musculoskeletal Oncology Group study. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  J. Casal,et al.  Proteomic expression analysis of colorectal cancer by two‐dimensional differential gel electrophoresis , 2005, Proteomics.

[18]  J. Seilhamer,et al.  A comparison of selected mRNA and protein abundances in human liver , 1997, Electrophoresis.

[19]  Z. Hall Cancer , 1906, The Hospital.

[20]  Q. Fan,et al.  Establishment and characterization of human osteosarcoma cell lines with different pulmonary metastatic potentials , 2009, Cytotechnology.

[21]  T. Miyazaki,et al.  Aldolase A isoenzyme levels in serum and tissues of patients with liver diseases. , 1983, Gastroenterology.

[22]  D. Sabatini,et al.  Cancer Cell Metabolism: Warburg and Beyond , 2008, Cell.

[23]  T. Tsuruo,et al.  Identification of genes differentially expressed in B16 murine melanoma sublines with different metastatic potentials. , 1996, Cancer research.