Proteomic profiling of proteins dysregulted in Chinese esophageal squamous cell carcinoma

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death in China. In the present study, proteins in tumors and adjacent normal esophageal tissues from 41 patients with ESCC were extracted, and two-dimensional electrophoresis (2-DE) was performed using the pH 3-10 and 4-7 immobilized pH gradient strips. The protein spots expressed differentially between tumors and normal tissues were identified by matrix-assisted laser desorption/ionization and liquid chromatography electrospray/ionization ion trap mass spectrometry. A total of 22 proteins differentially expressed between ESCC and normal esophageal tissues were identified, in which 17 proteins were upregulated and 5 downregulated in tumors. Biological functions of these proteins are related to cell signal transduction, cell proliferation, cell motility, glycolysis, regulation of transcription, oxidative stress processes, and protein folding. Some of the proteins obtained were confirmed by Western blotting and immunohistochemical staining. We showed that high expression of calreticulin and 78-kDa glucose-regulated protein (GRP78) were correlated with poor prognosis by Kaplan-Meier analysis and log rank analysis. Zinc finger protein 410, annexin V, similar to the ubiquitin-conjugating enzyme E2 variant 1 isoform c, mutant hemoglobin beta chain, TPM4-ALK fusion oncoprotein type 2, similar to heat shock congnate 71-kDa protein, GRP78, and pyruvate kinase M2 (M2-PK) were for the first time observed to be dysregulated in human ESCC tissues. The proteins here identified will contribute to the understanding of the tumorigenesis and progression of Chinese ESCC and may potentially provide useful markers for diagnosis or targets for therapeutic intervention and drug development.

Calreticulin promotes cell motility and enhances resistance to anoikis through STAT3–CTTN–Akt pathway in esophageal squamous cell carcinoma

“…CRT may have an important role in the development and/or progression of various human cancers: overexpression of CRT has been found in breast ductal carcinoma (Bini et al, 1997;Chahed et al, 2005), prostate adenocarcinoma (Alaiya et al, 2000), hepatocellular carcinoma (Kim et al, 2004) and colon cancer (Vougas et al, 2008). In ESCC, research by other groups and our previous finding suggests that CRT overexpression is a prevalent event in malignant transformation of esophageal epithelial cells (Nishimori et al, 2006;Du et al, 2007). Importantly, we observed that patients with CRT overexpression presented a shorter survival time compared to those with low CRT expression.…”

“…Our previous study identified 22 candidate proteins by proteomic analysis. Among them, we found that overexpression of Calreticulin (CRT) predicted a poor prognosis of ESCC patients (Du et al, 2007).…”

Renal cell carcinoma with novel VCL–ALK fusion: new representative of ALK-associated tumor spectrum

“…[15][16][17][18] More recently, the ALK gene has been shown to be involved in small subsets of epithelial malignancies, including carcinomas of pulmonary, esophageal, mammary gland, and gastrointestinal origin. [19][20][21][22] To the best of our knowledge, this is the first report of a recurrent ALK locus rearrangement in a primary kidney tumor. Although 2p23 chromosomal abnormalities have not been previously emphasized as recurrent in renal cell carcinoma, a review of the literature and search of the Mitelman database (http://www.ncbi.nlm.nih.gov/cancerchromosomes) yielded four additional primary renal carcinomas and one renal carcinoma cell line exhibiting karyotypic aberrations at or near the ALK gene 5,[33][34][35][36] (Table 4).…”

“…[19][20][21][22] The predicted structure and function of VCL-ALK oncoprotein follows the archetypical pattern defined by the combined properties of the N-terminal partner (ubiquitous expression and homopolymerization) and the C-terminal kinase domain (constitutive activation). On the basis of the current data, we propose that ALK fusion genes represent an oncogenic driver in a subset of renal cell carcinomas, and that recognition of these cases may be useful in ascertaining a patient's eligibility for emerging tyrosine kinase-targeted therapies, the clinical efficacy of which has been recently reported in a trial of ALK-positive non-small cell lung carcinoma.…”

“…11 Subsequently, ALK rearrangements were found in several phenotypically different hematologic neoplasms [12][13][14] and in histogenetically unrelated inflammatory myofibroblastic tumor. [15][16][17][18] Recently, ALK rearrangements and EML4-ALK and KIF5B-ALK fusions were discovered in a subset of non-small cell lung carcinomas; 19,20 proteomics reports suggested a possible TPM4-ALK fusion in esophageal carcinoma; 21,22 and an exon array profiling study demonstrated the EML4-ALK fusion in 2.5% of breast and colon cancers. 23 ALK is also activated in B5 to 35% of neuroblastomas and neuroblastoma cell lines by a different mechanism involving point mutations and/or gene locus amplifications.…”