Effect of miRNA-106a expression on the prognosis of patients with esophageal squamous cell carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the expression of miRNA-106a gene in esophageal squamous cell carcinoma (ESCC) and its association with clinicopathological features and prognosis of ESCC patients.</p><p><b>METHODS</b>Real-time fluorescence quantitative polymerase chain reaction (PCR) assay was used to determine the expression of miRNA-106a gene in esophageal cancer tissue and corresponding normal mucosa of 81 cases. Immunohistochemical technique was applied to detect the expression of p53, human epidermal growth factor receptor 2 (HER-2), DNA topoisomerase II (Topo II) and multidrug resistance-associated protein (MRP). The association of miRNA-106a expression with clinicopathological features, expression of related proteins, and prognosis of the patients was analyzed.</p><p><b>RESULTS</b>Among the 81 cases, under-expression of miRNA-106a gene was found in 48 cases (59.3%), normal expression in 22 cases (27.2%), and overexpression in 11 cases (13.6%). The expression of miRNA-106 gene was significantly associated with lymph node metastasis, pathological stage, and nerve invasion (all P < 0.05), significantly associated with expression of p53 (P = 0.006), and not significantly associated with expressions of HER-2, Topo II and MRP proteins (all P > 0.05). The expression of miRNA-106a gene was also significantly associated with progression-free survival (PFS, P = 0.032), but not significantly with overall survival (OS, P = 0.486). The results of Cox multivariate regression analysis showed that the PFS of ESCC patients was significantly correlated with lymph node metastasis (P = 0.029), but not correlated with the age, gender, tumor length, T stage, degree of differentiation, nerve invasion, and miRNA-106a expression (all P > 0.05).</p><p><b>CONCLUSIONS</b>In esophageal squamous cell carcinomas, the miRNA-106a gene is under-expressed, with tumor suppressor function, and may be regarded as a biological marker to assess the prognosis in patients with esophageal squamous cell carcinoma.</p>

Aberrant methylation of hMLH1 gene promoter in papillary thyroid cancer and its clinical significance / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the aberrant promoter methylation of hMLH1 gene promoter and its clinical significance in papillary thyroid cancer (PTC).</p><p><b>METHODS</b>methylation of hMLH1 gene promoter in the cancer tissue and matched tumor-adjacent normal tissue of 152 PTC patients were detected by real-time methylation specific PCR (qMSP). The relationship between the methylation of hMLH1 gene promoter and clinicopathological features was analyzed.</p><p><b>RESULTS</b>The methylation rate of hMLH1 gene promoter in cancer tissues was 37.5% (57/152), of which 33 cases were totally methylated and 24 cases were partially methylated. The methylation rate of adjacent normal tissues was 5.3% (8/152)(all were partially methylated). The methylation rate of PTC tissues was significantly higher than that in the tumor-adjacent normal tissue (P < 0.01). The promoter methylation of hMLH1 gene in PTC was significantly correlated with age, size and number of the primary lesion, local invasion, T stage and lymph node metastasis (P < 0.05) , but not correlated with gender and clinical stage (P > 0.05).</p><p><b>CONCLUSION</b>Promoter methylation of hMLH1 gene is a common molecular event in PTC tissue, and it is significantly correlated with the progression of PTC.</p>

Methylation status of CDH1 gene in preoperative abdominal lavage of patients with gastric cancer and its clinical significance / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the association between the progression of gastric cancer and the aberrant methylation of CDH1 gene in preoperative abdominal lavage fluid.</p><p><b>METHODS</b>Real-time methylation-specific polymerase chain reaction(qMSP) was used to investigate the methylation status of the CDH1 gene promoter 5'-CpG islands from preoperative abdominal lavage fluid in 92 patients with gastric cancer. The associations between methylation of CDH1 genes and clinicopathologic features and prognosis were investigated.</p><p><b>RESULTS</b>Among the 92 patients with gastric cancer, aberrant methylation of CDH1 gene was detected in 45(48.9%) patients, including total aberrant methylation in 12(13.0%) cases and partly aberrant methylation in 33(35.9%) cases. Significant associations were found between CDH1 methylation status and tumor size, growth pattern, differentiation, lymphovascular invasion, infiltration depth, lymph node metastasis, distant metastasis, and clinical staging(all P<0.05). However, there were no significant associations between CDH1 methylation status with gender, age, tumor location, or Helicobacter pylori infection(all P>0.05). The median progression-free survival was 20 months for CDH1 methylation group and 38 months for non-methylated group, and the difference was statistically significant(P<0.01). Cox model analysis revealed that CDH1 methylation status in preoperative peritoneal lavage fluid was an independent factor associated with postoperative survival in patients with gastric cancer(P=0.000, RR=332.88, 95%CI:21.71-5105.07).</p><p><b>CONCLUSIONS</b>The aberrant methylation of 5'-CpG of CDH1 gene promoter is common in gastric cancer. The examination of CDH1 methylation status of abdominal lavage should be considered in the progression of gastric cancer.</p>

DNA methylation status of RARβ2 and p16(INK4α) in peripheral blood and tumor tissue in patients with esophageal squamous cell carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the methylation status of retinoic acid receptor β2 (RARβ2) and p16(INK4α) genes in peripheral blood and tumor tissues and the perioperative dynamic changes of free RARβ2 and p16(INK4α) in the peripheral blood, and to investigate the relationship between RARβ2 and p16(INK4α) methylation in peripheral blood and clinicopathological characteristics of esophageal squamous cell carcinoma (ESCC) and their value in evaluating the completeness of surgical resection.</p><p><b>METHODS</b>Real-time methylation specific polymerase chain reaction (real-time MSP) technique was used to detect the methylation status of RARβ2 and p16(INK4α) in tumor tissue, adjacent normal tissue and peripheral blood perioperatively in 76 cases of ESCC. Sixty age-matched healthy volunteers were randomly selected as a control.</p><p><b>RESULTS</b>RARβ2 and p16(INK4α) hypermethylation presented in both tumor tissue [72.4% (55/76) and 86.8% (66/76)] and peripheral blood [63.2% (48/76) and 71.1% (54/76)] in the ESCC patients, showing a good agreement between them. RARβ2 and p16(INK4α) hypermethylation was significantly related with pathological stage, lymph node metastasis, and invasion of nerves and vessels (P < 0.05). The DNA methylation rate in peripheral blood was increasing first and then decreasing in the preoperative, intraoperative and postoperative periods. Moreover, the RARβ2 methylation in peripheral blood was shown to be significantly associated with family history of cancer (P = 0.023).</p><p><b>CONCLUSION</b>RARβ2 and p16(INK4α) methylation in the peripheral blood in ESCC patients may reflect the tumor-bearing status in the body, and may serve as a valuable marker in assessment of the degree of completeness of surgical resection in ESCC patients.</p>

Expression of epidermal growth factor receptor in salivary adenoid cystic carcinoma and its role in cancer invasion / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the epidermal growth factor receptor (EGFR) status in salivary adenoid cystic carcinoma and explore its role in cancer invasion.</p><p><b>METHODS</b>Fifty-four patients with pathologically confirmed salivary adenoid cystic carcinoma (SACC) were divided into invasion group and non-invasion group. The EGFR expression was determined by immunohistochemstry (SP staining). The relations between the EGFR expression and the SACC clinical pathological characteristics were analyzed.</p><p><b>RESULTS</b>EGFR were mainly expressed in the cell membrane and cytoplasm in the tissue of SACC. The positive rate of EGFR expression in the tumor tissue was 75.9% (41/54), and EGFR was over-expressed in the cytoplasm. The positive rate of EGFR expression in invasion group was higher than that in the non-invasion group (10.0%, P < 0.05). EGFR expression were related with the SACC T stages, histological types, distant metastasis, lymph node metastasis, and nerve invasion (P < 0.05).</p><p><b>CONCLUSIONS</b>A higher expression of EGFR gene in the cytoplasm may have important effect on the progression of invasive carcinoma. Further investigations are required to develop new strategy in the treatment of salivary adenoid cystic carcinoma.</p>

Expression of DNA methylation of APC in peripheral blood and tumor tissue in patients with esophageal squamous cell carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the relationship between methylation status of APC gene in both peripheral blood and tumor tissues and clinical-pathology characteristics in patients with esophageal squamous cell carcinoma(ESCC), and to study the dynamic change of APC methylation in peripheral blood in the perioperative period.</p><p><b>METHODS</b>Real-time MSP technique was used to detect methylation status of APC in tumor tissues, adjacent normal tissues and peripheral blood on the day before the surgery, intraoperative, postoperative day 7 in 76 cases with ESCC. Sixty healthy volunteers matched by age and gender were randomly selected as controls.</p><p><b>RESULTS</b>The methylation rate of APC in tumor tissue and peripheral blood was 44.74%(34/76) and 42.11%(32/76), respectively, which were significantly higher than that in adjacent normal tissue and controls [6.58%(5/76) and 1.67%(1/60), P=0.000]. The methylation rates showed good agreement between tumor tissues and peripheral blood, which could be verified by ROC curve(A Zeta=0.849, P=0.000). APC methylation rate was significantly related to pathological staging, lymph node metastasis, depth of invasion, and invasion of nerve and vessel (P<0.05). The results demonstrated that family history of cancer was independently associated with APC methylation in peripheral blood(P<0.05). DNA methylation rates in peripheral blood showed an initial increase and then decreased in the preoperative period, intraoperative and postoperative.</p><p><b>CONCLUSION</b>The methylation rates of APC among free DNA in peripheral blood in patients with ESCC reflect tumor progression, and decrease with the solid tumour resection.</p>

Impact of lymphocytes subgroups in peripheral blood on survival rate of patients with gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the change of lymphocyte subgroups in the peripheral blood of patients with gastric carcinoma and its association with survival.</p><p><b>METHODS</b>Flow cytometry was used to examine the subgroups of lymphocytes (CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), CD19(+), CD25(+), CD44(+) and NK cells) in the peripheral blood of 833 gastric carcinoma patients prior to any therapy. Patients were divided into the high expression group and lower expression group according to the average test values of 96 healthy control subjects. Survival rate was compared between the two groups.</p><p><b>RESULTS</b>Compared with control group, the levels of CD3(+) and CD8(+) T cell in patients were significantly lower, while the levels of CD4(+), CD19(+), CD25(+), CD4(+)/CD8(+), CD44(+), and NK(+) cells were significantly. The differences were statistically significant(P<0.05). Three-year survival rates of gastric cancer patients with high CD19(+) expression (n=444) and cases with low CD19(+) expression (n=389) were 36.4% and 18.5%, respectively(P<0.05). The expressions of other seven types of lymphocytes were not associated with survival rates (all P>0.05).</p><p><b>CONCLUSIONS</b>Significant changes in lymphocyte subgroups exist in the peripheral blood of patients with gastric carcinoma. Patients with high CD19(+) expression have better survival.</p>

Evolution pattern of the Runx3 gene 5'-CpG island methylation in human salivary gland adenoid cystic carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the evolution pattern of the Runx3 gene 5'-CpG island ~3478 bp region methylation in human salivary gland adenoid cystic carcinoma (SGACC).</p><p><b>METHODS</b>Quantitative MSP method was used to detect the methylation status of CpG island in various regions (No.1-10) of Runx3 promoter region, and Western blot was used for detection of the expression of Runx3 protein in 41 salivary gland SGACC samples and corresponding non-neoplastic salivary gland tissues. A Logistic model was used to analyze the risk ratio between the methylation status of CpG island in Runx3 gene and development of salivary SGACC, meanwhile, the possible association among the methylation of Runx3 gene, the clinicopathological parameters of SGACCs, and Runx3 protein expression was compared.</p><p><b>RESULTS</b>The results of qMSP showed that the hypermethylation initially occurred at the most 5' region of the Runx3 CpG island and spread to the transcription start site. The methylation rate was highest in region No. 1 and No. 2 among the successive ten regions ranging from the 5' region to the transcription start site within the Runx3 CpG island, and lowest in the transcription start site both in SGACCs and normal salivary glands. Furthermore, there was no methylation in the transcription start site in nomal salivary glands tissues. Together with the results of Logistic model analysis, those results indicate that the transcription start site within the Runx3 promoter CpG island is critical for gene silencing. Western blot results revealed that the Runx3 protein level in SGACC was significantly lower than that in normal salivary glands (P < 0.01). In combination of the results of qMSP, it is presumed that the Runx3 gene methylation is one of the reason inducing the down-regulation of Runx3 in SGACCs.</p><p><b>CONCLUSIONS</b>Methylation of the Runx3 CpG island spreads from the most 5'-region to the transcription start site in human salivary gland adenoid cystic carcinoma, and the transcription start site may be a critical region for the methylation of Runx3. The evolution pattern of Runx3 gene methylation is related to the tumorigenesis of SGACCs.</p>

cDNA microarray-based study of gene expression profile changes in human esophageal squamous cell carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the differentially expressed genes between human esophageal squamous cell carcinoma (ESCC) and normal esophageal mucosa and explore an effective method with high throughput for screening the molecular markers closely correlated with the development, invasion and metastasis of ESCC.</p><p><b>METHODS</b>With cDNA microarray and laser capture microdissection, T7-based amplification were used to detect the mRNA from both the primary carcinoma and the corresponding esophageal epithelium in 15 ESCC cases, and the results were analyzed by bioinformatics methods.</p><p><b>RESULTS</b>Among the 886 target genes, 110 (12.42%) genes were differentially expressed commonly at least twice in all the 15 samples, including 56 (6.32%) up-regulated by at least 2 folds and 54 (6.09%) down-regulated by at least 0.5 folds.</p><p><b>CONCLUSION</b>Many ESCC-associated genes were screened by the high-throughput gene chip method, and functional study of these genes may help to identify the key genes or pathways involved in the pathogenesis and development of ESCC.</p>

Study on serum levels of E- selectin, integrin beta 1 subunit and intercellular adhesion molecule-1 in gastric cancer patients and their clinical implications / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the serum concentrations of E- selectin, integrinbeta(1) subunit and intercellular adhesion molecule-1 in gastric cancer patients and their clinicopathological significance.</p><p><b>METHODS</b>The serum levels of adhesion molecules E- selectin,intercellular adhesion molecule- 1 (ICAM- 1), and integrinbeta(1) were measured by enzyme-linked immunosorbent assay (ELISA) in 47 health subjects (control group) and in 57 patients with gastric cancer (gastric cancer group) before operation and 7 days after operation. Serum levels of above three factors were compared between the two groups.</p><p><b>RESULTS</b>The serum concentrations of E- selectin, integrinbeta(1) subunit and ICAM- 1 were higher in gastric cancer group with positive rate of 24.6% ,33.3% ,28.1% respectively. ICAM- 1 and integrinbeta(1) were significant higher in gastric cancer group than that in the control group (P< 0.01),but there was no significant difference in E- selectin between two groups (P=0.64). Serum concentrations of E-selectin, ICAM-1,and integrinbeta(1) were significantly correlated with clinicopathological features as following: clinicopathological stage,invasion depth,lymph node involvement,and presence of distant metastases(P< 0.05,P< 0.01). The serum levels of E- selectin, ICAM- 1, and integrinbeta(1) were decreased significantly after radical resection of gastric cancer,but not in patients with unresectable tumor. Elevated levels of three molecules were significant prognostic factors for patients with gastric cancer,but it could not independently be used to evaluate tumor stage.</p><p><b>CONCLUSIONS</b>Serum concentrations of E- selectin, ICAM- 1,and integrinbeta(1) may reflect tumor progression and metastasis.</p>