Analysis of XPD genetic polymorphisms of esophageal squamous cell carcinoma in a population of Yili Prefecture, in Xinjiang, China.

To evaluate the association with genetic polymorphisms in Xeroderma pigmentosum complementation group D (XPD) gene of esophageal squamous cell carcinoma (ESCC) risk in a population of Yili Prefecture, in Xinjiang, China. A hospital-based case-control study was designed with 571 samples including 213 ESCC patients and 358 controls with age, gender and ethnicity-matched subjects (Kazakh, Uygur and Han ethnic). Genotypes were determined by PCR restriction fragment length polymorphism (PCR-RLFP) and confirmed by sequence. Relative risk associated with a particular genotype was estimated by calculating odds ratios (OR) along with 95% confidence intervals (CI). Significant ESCC risk was observed for XPD Lys751Gln (rs13181) frequency of presence C allele (OR: 1.409, 95% CI: 1.005-1.976) in the three ethnics. XPD Asp312Asn (rs1799793) of Han ethnic was associated with a borderline decrease of ESCC (OR: 0.362, 95% CI: 0.145-0.906), however, it was associated with ESCC risk in Uygur ethnic (OR: 2.403, 95% CI: 1.087-5.310). The results demonstrated an association between the XPD Lys751Gln (rs13181) for frequency of presence C allele and risk for ESCC in the three ethnics of Yili Prefecture, in Xinjiang, China. XPD Asp312Asn (rs1799793), which was associated with a borderline decrease of Han ethnic and risk of Uygur ethnic of ESCC, may play a different role in the three ethnics of ESCC.

Clinicopathological pattern and Annexin A2 and Cdc42 status in patients presenting with differentiation and lymphnode metastasis of esophageal squamous cell carcinomas.

Annexin A2 and Cdc42 were identified by 2-dimensional electrophoresis (2-DE) and MALDI-TOF-MS between esophageal squamous cell carcinomas (ESCC) and corresponding normal esophagus mucosa in our previous study. To assess clinico-pathological pattern and Annexin A2 and Cdc42 status with respect to cell differentiation and lymphnode metastasis in patients with ESCC. The expression of Annexin A2 and Cdc42 in 22 pairs of fresh ESCC and matched tissues were detected by qRT-PCR and western blot, respectively. And it was further confirmed by immunohistochemistry with 175 pairs of formalin-fixed, paraffin-embedded ESCC. Results showed that Annexin A2 expression was significantly down-regulated, and Cdc42 was up-regulated in ESCC compared to matched control on both mRNA and protein level (P < 0.05), which was in accordance with our previous results on proteomics data. Additionally, Annexin A2 and Cdc42 expression was significantly correlated with lymphoid node metastasis (P < 0.05) and pathological differentiation (P < 0.05). Taken together, we proposed that the aberrant expression of Annexin A2 and Cdc42 played a role in carcinogenesis, differentiation and metastasis of ESCC, which implied its potential target for clinical biomarkers in differentiation and lymph node metastasis.

Polymorphisms of COMT and XPD and risk of esophageal squamous cell carcinoma in a population of Yili Prefecture, in Xinjiang, China.

OBJECTIVE: To investigate polymorphisms of COMT (Rs4680) and XPD (Rs13181) and risk of esophageal squamous cell carcinoma (ESCC) in a population from Yili Prefecture, Xinjiang, China. METHODS: A hospital-based case-control study was designed. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratios (OR) and 95% confidence intervals (CI) were analysed using unconditional logistic regression. RESULTS: An increased risk of ESCC was discovered with COMT in relation to the frequency of the presence of the A allele (Rs4680; OR 1.30, 95% CI 1.00-1.68). An individual with combined COMT 158 (Val/Met or Met/Met) and XPD 751 (Lys/Gln or Gln/Gln) genotype had an increased ESCC risk. CONCLUSIONS: Polymorphic variation in COMT Val158Met and XPD Lys751Gln may be important for ESCC susceptibility.

Role of microRNA-21 and effect on PTEN in Kazakh's esophageal squamous cell carcinoma.

The aim of this study was investigate the role of microRNA-21 (miR-21) and its regulation on phosphatase and tensin homolog deleted from chromosome-10 (PTEN) in Kazakh's esophageal squamous cell carcinoma (ESCC). MiR-21 expressions were investigated in esophageal cancer cell line Eca109, and 18 pairs of Kazakh's ESCC and adjacent normal tissues by real-time quantitative PCR (qRT-PCR). To evaluate the role of miR-21 and PTEN, cell proliferations were analyzed with miR-21 mimics or their inhibitor-transfected cells. Moreover, the expressions of PTEN were performed by Western blotting. In Eca109, when transfected with miR-21 mimics, accumulation of miR-21 was obviously increased and expression of PTEN protein was decreased to be approximately 40%, which resulted in the promotion of cell proliferation. However, when transfected with miR-21 inhibitor, expression of miR-21 was declined and PTEN protein was overexpressed to be approximately 79%, which resulted in the suppression of cell proliferation. Both of them had no effect on the level of PTEN mRNA. Compared with adjacent normal tissues, miR-21 expression was significantly higher in tumor (P < 0.05). Specifically, patients with cancer cell invasion deep into esophageal serosa showed significantly higher expression of miR-21. Protein expression of PTEN was significantly lower in tumor compared with normal tissues (P < 0.05); however, mRNA expression of PTEN had no obvious significance between them. Furthermore, there was a significantly inverse correlation between miR-21 expression and PTEN protein levels (p < 0.05). The author concluded that MiR-21 was overexpressed in vitro and ESCC, and promoted the cell proliferation, might target PTEN at post-transcriptional level, and regulated the cancer invasion in Kazakh's ESCC.

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

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.

[Expression of ERK1/2 MAPK signaling transduction pathway in esophageal cancers in Kazakh patients].

OBJECTIVE: To investigate the expression variation and significance of ERK1/2 MAPK signaling transduction pathway in the pathogenesis of esophageal squamous cell carcinoma (ESCC) in Kazakh patients. METHODS: The expression level of p-ERK1/2 after serum starvation and treatment with U0126 inhibitor was detected in esophageal cancer cell line EC9706 by Western blot assay. The mRNA level of total ERK1/2 (t-ERK1/2) and expression level of t-ERK1/2 and p-ERK1/2 proteins of 25 pairs of ESCC and adjacent normal esophageal mucosal tissues of Kazakh patients were examined and identified by real-time quantitative PCR (qRT-PCR) and Western blotting, respectively. The expression of p-ERK1/2 protein was verified by immunohistochemistry in 126 paraffin-embeded specimens, including 19 normal esophageal mucosa, 55 esophageal carcinomas in situ and 52 invasive carcinomas. RESULTS: ERK1/2 MAPK signaling transduction pathway was in an active status in the EC9706 cells. The expression level of p-ERK1/2 in Ec9706 cells reached a peak at 10 min after transient serum stimulation, and p-ERK1/2 expression was totally restrained after the treatment with 50 µmol/L U0126. In the 25 pairs of ESCC and adjacent normal mucosa, the t-ERK1 mRNA level was 1.92 ± 3.49 in the ESCC tissues and 3.67 ± 7.47 in the adjacent normal mucosa. The t-ERK1 mRNA level in ESCC tissues was significantly lower than that in adjacent normal mucosa (P < 0.05), whereas there was no significant difference of t-ERK2 mRNA level between them(P > 0.05). The expression levels of p-ERK1 and p-ERK2 proteins were 0.87 ± 0.14 and 0.79 ± 0.10 in the ESCC tissues, and 1.10 ± 0.13 and 1.32 ± 0.12 in the adjacent normal mucosae. p-ERK1/2 protein in the ESCC tissues was significantly lower than that in the adjacent normal tissue (P < 0.01). However, there was no significant difference between their t-ERK1/2 protein levels (P > 0.05). In the 126 cases of paraffin-embeded specimens, positive expressions of both p-ERK1 and p-ERK2 in esophageal cancer tissues were 7.7% (4/52), significantly lower than those in adjacent normal mucosa (31.6%, 6/19) and carcinoma in situ (85.5%, 47/55, P < 0.05). CONCLUSIONS: ERK1/2 MAPK signaling pathway is in an active status in esophageal cancer and adjacent normal mucosa. Our results imply that the activation of p-ERK1/2 MAPK signaling transduction pathway plays a role in the early pathogenesis of ESCC in Kazakh patients.