Non-neoplastic Mucosal Tissues Research Articles

RETRACTED ARTICLE: Differences in the expression profiles of claudin proteins in human nasopharyngeal carcinoma compared with non-neoplastic mucosa

BackgroundSeveral studies have suggested that claudin proteins, which are the main components of tight junction structures, are related to the regulation of cell polarity and cell differentiation.MethodTo explore the expression profiles of the tight junction proteins claudin-2, − 5, − 8 and − 9 in nasopharyngeal carcinoma, IHC (immunohistochemical analysis), Western blot and real-time PCR were used to detect the expression profiles of these claudin proteins in nasopharyngeal carcinoma tissues and in non-neoplastic mucosal tissues.ResultsAccording to our study, the expression levels of claudin-2 and claudin-5 were reduced, while the expression of claudin-8 was increased in nasopharyngeal carcinoma tissues in comparison with non-neoplastic mucosal tissues. Correlations between claudin-2 and -5 expression and metastatic progression in nasopharyngeal carcinoma patients were also found.ConclusionIn summary, our research reveals distinct expression profiles of claudin-2, − 5 and − 8 in non-neoplastic mucosal tissues and nasopharyngeal carcinoma tissues. In addition, the expression of these claudin proteins was highly correlated with metastatic progression and prognosis in patients with nasopharyngeal carcinoma and had predictive value for the metastasis and survival of nasopharyngeal carcinoma patients.

Prognosis of stage III colorectal carcinomas with FOLFOX adjuvant chemotherapy can be predicted by molecular subtype.

Individualizing adjuvant chemotherapy is important in patients with advanced colorectal cancers (CRCs), and the ability to identify molecular subtypes predictive of good prognosis for stage III CRCs after adjuvant chemotherapy could be highly beneficial. We performed microarray-based gene expression analysis on 101 fresh-frozen primary samples from patients with stage III CRCs treated with FOLFOX adjuvant chemotherapy and 35 matched non-neoplastic mucosal tissues. CRC samples were classified into four molecular subtypes using nonnegative matrix factorization, and for comparison, we also grouped CRC samples using the proposed consensus molecular subtypes (CMSs). Of the 101 cases, 80 were classified into a CMS group, which shows a 79% correlation between the CMS classification and our four molecular subtypes. We found that two of our subtypes showed significantly higher disease-free survival and overall survival than the others. Group 2, in particular, which showed no disease recurrence or death, was characterized by high microsatellite instability (MSI-H, 6/21), abundant mucin production (12/21), and right-sided location (12/21); this group strongly correlated with CMS1 (microsatellite instability immune type). We further identified the molecular characteristics of each group and selected 10 potential biomarker genes from each. When these were compared to the previously reported molecular classifier genes, we found that 31 out of 40 selected genes were matched with those previously reported. Our findings indicate that molecular classification can reveal specific molecular subtypes correlating with clinicopathologic features of CRCs and can have predictive value for the prognosis for stage III CRCs with FOLFOX adjuvant chemotherapy.

Expression of centromere protein H and its correlation with clinicopathological features and prognosis in gastric cancer

Objective To explore the expression of centromere protein H (CENP-H) and its correlation with clinicopathological features of gastric cancer (GC).Methods The expression level of CENP-H in 9 caes of gastric cancer tissue and corresponding normal mucosal tissue was detected by real-time quantitative polymerase chain reaction (Real-time PCR) and Western blotting.CENP-H expression levels in specimens from 166 patients with GC and nonneoplastic mucosal tissue were determined by immunohistochemical staining.The correlations between CENP-H with clinicopathologic features and prognosis was analyzed.Results It was dearly showed that the mRNA and protein expression of CENP-H was elevated in tumor tissue samples as compared with that in nonneoplastic mucosal tissue (P ＜ 0.05).The CENP-H expression was positive in 85 of 166 cases of GC,and negative in all nonneoplastic mucosal tissues,showing a significant correlation with tumour size (P ＜ 0.05),depth of infiltration (P ＜ 0.01),lymph node metastasis (P ＜ 0.01) and TNM staging (P ＜0.01) of GC,as well as clinical prognosis (P ＜0.01).Log-rank test indicated that 5-year survival rate of patients with high CENP-H expression was significantly lower than that of patients with low CENP-H expression.Multivariate Cox regression analysis confirmed that CENP-H (P ＜0.05),lymph node metastasis (P ＜ 0.01) and TNM staging (P ＜ 0.01) were independent prognostic predictors for patients with GC.Conclusion Our data suggested that CENP-H might play a role as a cancer gene and that its high expression indicated a poor prognosis in GC. Key words: Centromere protein H; Gastric Carcinoma; Prognosis

CpG island methylator phenotype andHelicobacter pyloriinfection associated with gastric cancer

To investigate the association between the CpG island methylator phenotype (CIMP) and serum Helicobacter pylori (H. pylori) levels for clinical prediction of gastric cancer (GC) progression. We analyzed the serum CIMP status of 75 patients with GC using a methylation marker panel and a methylation-specific polymerase chain reaction. Serum samples from 40 healthy persons were examined at the same time. The genes examined were APC, WIF-1, RUNX-3, DLC-1, SFRP-1, DKK and E-cad. H. pylori infection in serum was assayed with an anti-H. pylori immunoglobulin G antibody test and a rapid urease test. The frequencies of high-level methylation in GC tissues for the seven genes were: 48% for APC, 57.33% for WIF-1, 56% for RUNX-3, 50.67% for DLC-1, 52% for SFRP-1, 54.67% for DKK, and 48% for E-cad. The frequencies in GC serum were 30.67% for APC, 34.67% for WIF-1, 37.33% for RUNX-3, 29.33% for DLC-1, 33.33% for SFRP-1, 32% for DKK, and 26.67% for E-cad. CIMP+ (defined as ≥ 3 methylated genes) was associated with 47 (62.67%) GC tissue samples and 44 (58.67%) GC serum samples. CIMP+ was not associated with non-neoplastic mucosal tissues or the serum of healthy persons. Of the 75 GC cases, 51 (68%) were H. pylori+, and 24 (32%) were H. pylori-. Of the 51 H. pylori+ cases, 36 were CIMP+ and 15 were CIMP-. In contrast, for the 24 H. pylori- cases, 11 were CIMP+, and 13 were CIMP-. The difference was significant between the H. pylori+ and H. pylori- groups (χ(2) = 4.27, P < 0.05). Of the 51 H. pylori+ GC patients, 34 were CIMP+ and 17 were CIMP-, while among the 24 H. pylori- GC cases, 10 were CIMP+ and 14 were CIMP-. The difference was significant between the H. pylori+ and H. pylori- groups (χ(2) = 4.21, P < 0.05). A 2-year follow-up showed significant difference in the rates of metastasis and recurrence between H. pylori+/CIMP+ cases and the H. pylori+/CIMP- cases or CIMP- cases associated with H. pylori assayed in serum (P < 0.05). However, there were no significant differences in survival rates between the two groups. H. pylori+/CIMP+ cases are associated with higher rates of metastasis and recurrence than H. pylori+/CIMP- cases. Serum may be useful for examining CIMP status.

Enhanced S100A4 protein expression is clinicopathologically significant to metastatic potential and p53 dysfunction in colorectal cancer

To investigate the expression levels of S100A4 in human colorectal carcinoma (CC) and its relationship with clinicopathological parameters and metastatic potential, 73 pathological specimens from patients with CC were examined for S100A4 expression by RT-PCR and immunohistochemistry. An increase of S100A4 mRNA was observed in 19/23 (82.6%) CC specimens, and S100A4 was up-regulated in 40/73 (54.7%) CC cases compared with non-neoplastic mucosal tissues. Upregulation of S100A4 was significantly related to invasion, nodal status, distant metastasis and p53 expression. Next, we investigated whether S100A4 could affect p53 transactivation and stability. Interestingly, it was revealed that treatment with exogenous S100A4 protein reduced transcriptional activity of p53 and abrogated the modification of calcium binding affinity of S100A4 protein. These findings suggested that S100A4 might be involved in the progression and metastasis of human CC, presumably via modulation of the wild-type p53 protein.

Nm23 protein expression in colorectal carcinoma metastasis in regional lymph nodes and the liver

Aims The nm23 gene has been shown to have metastasis suppressing activity and abnormalities of the gene or its expression may be important in tumour progression and dissemination. This study was set out to investigate the possible role of the nm23 in colorectal adenocarcinoma dissemination by examining the level of nm23 protein expression in colorectal carcinoma metastasis in regional lymph nodes and the liver. Methods Using a monoclonal antibody, NCL-nm23 (Novocastra), immunohistochemical expression of the nm23 protein was examined in cases of metastatic colorectal adenocarcinoma in regional lymph nodes (n=71) and liver (n=36). Results The cases of lymph-node metastasis also had tissues from the primary carcinoma (n=71) and matching normal non-neoplastic mucosal tissues (n=71) from the colon and rectum available for the study. More than half of the cases of primary colorectal carcinoma (43/71; 60%) displayed strong nm23 immunoreactivity, with a similar proportion of the lymph-node metastases (40/71 cases; 56%) having strong nm23 immunostaining. However, only a small minority of the normal controls of non-neoplastic colorectal epithelia (12/71 cases; 17%) had strong nm23 immunoreactivity. The difference in nm23 protein expression between normal colorectal mucosa and primary colorectal carcinoma was statistically significant (P=0.0001; chi-squared test with continuity correction). However, no significant difference in nm23 protein expression was found between primary colorectal carcinoma and lymph-node metastases (P=0.81; chi-squared test with continuity correction). Most of the liver metastases (24/36 cases; 67%) had strong nm23 immunostaining but this finding was not statistically significant when compared with that seen in primary colorectal carcinoma (P=0.62; chi-squared test with continuity correction). In addition, nm23 expression was not found to significantly correlate with 5-year survival of patients with liver metastasis (P=0.86), suggesting that it had no predictive value for overall patient survival. There was also no significant correlation between disease recurrence and nm23 expression (P=0.63).Conclusions In summary, increased nm23 protein immunoreactivity is seen in the majority of colorectal carcinomas when compared to normal colorectal tissues but no significant difference in nm23 expression was found between primary colorectal carcinoma and metastatic carcinoma in regional lymph nodes or the liver. This study suggests that increased nm23 expression may be important in early colorectal carcinoma but not in later progression and dissemination of the tumour. In conclusion, the role and importance of the nm23 gene in the development of tumour metastasis in colorectal carcinoma is questionable.