Proteomic identification of differentially-expressed proteins in esophageal cancer in three ethnic groups in Xinjiang

Abstract

The Objective is to identify candidate biomarkers for Squamous cell carcinoma (ESCC) in three ethnics in Xinjiang as well as reveal molecular mechanism. Proteins from 15 pairs of ESCC and matching adjacent normal esophageal tissues (five pairs in each ethnic of Kazakh, Uygur and Han) were separated by 2-DE and differentially proteins were identified by matrix-assisted laser desorption/ionization time-of-flight MS. After identified by Mascot database, some of interesting proteins were confirmed in the other 175 pairs of ESCC by immuno histochemistry. Comparison of patterns revealed 20 proteins significantly changed, of which 12 protein with concordantly increased, such as ACTB protein, COMT protein, Syntaxin binding protein Pyruvate Kinase (PKM2), Cathepsin D, Chromosome 1 open reading frame 8, Heat shock protein 27, Cdc42, Proteosome, LLDBP, Immunoglobulin, TNF receptor associated factor 7; and eight protein spots with concordantly decreased intensity in ESCC, such as Adenylate kinase 1, General transcription factor II H, Smooth muscle protein, Trangelin, Early endosome antigen 1, Annexin A2, Fibrin beta, Tropomyosin. There were a significant difference in protein overexpression of PKM2 (74.9%) and Cathepsin D (85.1%) in ESCC compared to adjacent tissues (P < 0.05) by immunohistochemistry. Further, overexpression of Cathepsin D was obvious difference in Hazakh ESCC (94.7%) than that in Uygur (78.6%) (P < 0.05). Interestingly, the overexpression of Cathepsin D was reversely associated with ESCC differentiation (P < 0.05). Twenty proteins differentially-expressed between ESCC and normal tissues were identified. Cathepsin D and PKM2 were for the first time observed to be dysregulated in Kazakh's ESCC. Moreover, Cathepsin D may play a complicated role both in carcinogenesis and cell-differentiation of ESCC.

Proteomic Study of Esophageal Squamous Cell Carcinoma

“…The commonly identified proteins with the same change direction included alpha enolase, TPM, tubulin, prohibitin and PRX2. Although the prevalence of ESCC in Xinjiang is comparable to Linzhou, the protein signatures were unique to sample origin, indicative of more important roles of environmental, ethnic or hereditary factors in the carcinogenesis of ESCC [Liu et al, 2011]. It seems that hsp27 was a general molecular events involved in ESCC since four out of five studies observed down-expression in ESCC except ours.…”

“…Our findings indicate that MIF may play crucial roles in malignant transformation of pathogenesis of EC and MIF could become a potential biomarker for high-risk population screening, assessment of therapeutic efficiency, prognostic evaluation, and molecular targets of developing novel therapeutic regimen as well. In addition of our proteomic results in ESCC, several other reports have looked at the clinical value of potential biomarkers, including cytokeratin 14, Annexin I, SCCA1/2, calgulanulin B and HSP 60, alpha-actinin 4 and 67 kDa laminin receptor, cathepsin D and PKM2, periplakin, calreticulin and GRP78, galectin-7, anti-CD25B antibody [Dong et al, 2010;Du et al, 2007;Fu et al, 2007;Hatakeyama et al, 2006;Liu et al, 2011;Nishimori et al, 2006;Zhu et al, 2010]. Nevertheless, further extensive studies are still necessary to determine the clinical utility of the identified proteins in tumorigenesis and progression of ESCC.…”

“…↑or ↓ Calcium-dependent phospholipid binding calcium ion binding [Du et al, 2007;Liu et al, 2011] Annexin A8 ↓ [Nishimori et al, 2006] Annexin I ↓or↑ [Du et al, 2007;Jazii et al, 2006;Liu et al, 2011;Nishimori et al, 2006;Zhou et al, 2005;Zhu et al, 2010 [Du et al, 2007;Nishimori et al, 2006] DnaJ(Hsp40) homolog ↑ [Nishimori et al, 2006] www.intechopen.com…”

“…Heat shock protein 27 kDa ↓ or ↑ [Du et al, 2007;Fu et al, 2007;Liu et al, 2011; [Qi et al, 2005] www.intechopen.com…”

Comparisons of Curative and Side Effects of Chemoradiotherapy among Xinjiang Han, Uigur and Kazakh Esophageal Carcinoma Patients

“…There, minority patients occupy a great proportion of all EC patients, among which the highest incidence is found in Kazakh population and the second in Uigurs (Zhou et al, 2009). Minority EC patients are different from Han patients in living habits and constitution, and the pathogenesis of EC among minorities is also somewhat different from that among Hans (Liu et al, 2011). In China, esophageal squamous cell carcinoma is the major pathological form of EC and esophageal adenocarcinoma only accounts for 0.4% of EC cases (Zou et al, 2002).…”