Expression of UbcH10 in pancreatic ductal adenocarcinoma and its correlation with prognosis

The aim of this current study was to investigate the clinicopathologic features and prognostic significance of UbcH10 in pancreatic ductal adenocarcinoma (PDA). Real-time quantitative RT-PCR was employed to examine UbcH10 expression in 20 pairs of PDA and adjacent non-cancerous tissues. In addition, UbcH10 expression was analyzed by immunohistochemistry in 94 clinicopathologically characterized PDA cases. The correlation of UbcH10 expression with patients’ survival rate was assessed by Kaplan–Meier and Cox regression. Our results showed that the expression levels of UbcH10 mRNA and protein in PDA tissues were both significantly higher than those in non-cancerous tissues. Simultaneously, high expression of UbcH10 was significantly correlated with the clinical stage (p?<?0.001), degree of histological differentiation (p?<?0.001), and lymph node metastasis (p?=?0.001). Moreover, high expression of UbcH10 was significantly associated with poor overall survival in PDA patients. In conclusion, UbcH10 might play a positive role in tumor development and could serve as an independent predictor of poor prognosis for PDA.     

Pyrophosphatase overexpression is associated with cell migration, invasion, and poor prognosis in gastric cancer

Inorganic pyrophosphatase (PPase) catalyzes the hydrolysis of pyrophosphate to form orthophosphate. Pyrophosphate can substitute for ATP under certain circumstances. We previously conducted a proteomic analysis to investigate tumor-specific protein expression in gastric cancer, and PPase was identified as a potential gastric tumor-specific marker; it was therefore selected for further study. Clinicopathological analysis, using proteomic analysis and immunohistochemistry, was used to validate PPase as a prognostic marker in gastric cancers. Proteomic analysis showed that PPase was overexpressed in patients with lymph node (LN) metastases and high tumor node metastasis (TNM) stages (p?<?0.05). Based on immunohistochemistry, patients whose tumors overexpressed PPase had higher T stages, LN metastasis, a higher TNM stage, a higher cancer recurrence rate, and shorter survival times than patients whose tumors exhibited PPase underexpression (p?<?0.05). Gain-of-function and loss-of-function approaches were employed to examine the malignant phenotypes of PPase-overexpressing or PPase-depleted cells. A decrease in PPase expression caused a significant decrease in gastric cancer cell migration and invasion in vitro, whereas forced overexpression of PPase enhanced migration but not invasion. Our findings indicate that PPase is involved in gastric tumor progression and that PPase may be a useful marker for poor prognosis of human gastric cancers.     

Elevated expression of iASPP in head and neck squamous cell carcinoma and its clinical significance

iASPP is shown to be elevated in several cancers. However, the role of iASPP in head and neck squamous cell carcinoma (HNSCC) remains unknown. We have investigated iASPP expression in HNSCC tissue and cell lines and evaluated its prognostic significance in HNSCC. The expression of iASPP in 109 primary HNSCC tissue specimens was examined by immunohistochemistry and its association with clinicopathological parameters and prognosis was analyzed. Additionally, expression status of iASPP in 16 paired HNSCC tissues and 7 HNSCC cell lines was evaluated by quantitative real-time PCR (qPCR) and immunoblotting. The protein and mRNA expression of iASPP were increased in HNSCC tissues and cell lines. Immunohistochemical staining indicated iASPP was detected in both cytoplasm and nucleus. Importantly, overexpression of cytoplasmic and nuclear iASPP was significantly associated with T classification (p?=?0.002 and p?=?0.033, respectively), clinical stage (p?<?0.001 and p?=?0.004), lymph node metastasis (p?=?0.001 and p?<?0.001), and recurrence (both p?<?0.001). Survival analysis demonstrated high iASPP expression significantly correlated with shorter disease-free survival (DFS) (both p?<?0.001 for cytoplasmic and nuclear expression) and overall survival (OS) (both p?<?0.001 for cytoplasmic and nuclear expression). Multivariate analysis revealed that cytoplasmic iASPP was the only independent prognostic factor for HNSCC patients. iASPP expression is elevated in HNSCC tissues and cell lines, which suggests iASPP may contribute to the malignant progression of HNSCC, and serves as a novel prognostic marker and a potential therapeutic target in HNSCC.     

Reduced N-Myc downstream-regulated gene 2 expression is associated with CD24 upregulation and poor prognosis in patients with lung adenocarcinoma

N-Myc downstream-regulated gene 2 (NDRG2) has been demonstrated to influence the metastatic potential of hepatocellular carcinoma and breast cancer cells by regulating CD24 expression. The aim of this study was to investigate the roles of NDRG2 and CD24 in the clinical pathology of lung adenocarcinoma and to explore whether the expression of these two markers can be used as independent factors for the prediction of prognosis in patients with this tumor. NDRG2 and CD24 expression in paraffin-embedded specimens gathered from 166 patients with lung adenocarcinoma was detected by immunohistochemical method. The correlation of these two proteins expression with clinicopathological parameters and prognosis was statistically analyzed. NDRG2 and CD24 proteins were highly expressed in 59/166 (35.5?%) and 110/166 (66.3?%) of lung adenocarcinoma patients, respectively. High expression of NDRG2 was frequently found in lung adenocarcinoma tissues in early pTNM stage (p?=?0.01) and without pathological metastasis (p?=?0.02), whereas the high expression of CD24 was significantly associated with the advanced pTNM stage (p?=?0.04) and pathological metastasis (p?=?0.01). Univariate analysis indicated that the patients with NDRG2 high expression correlated with favorable prognosis in patients with lung adenocarcinoma (p?=?0.001), as opposed to CD24 (p?=?0.001). The survival rate of the patients with NDRG2-low/CD24-high expression was the lowest (p?<?0.001). Multivariate statistical analysis showed that the conjoined expressions of NDRG2-high/CD24-low and NDRG2-low/CD24-high were independent prognostic indicators of lung adenocarcinoma (p?=?0.03 and p?=?0.02, respectively). Our results suggest that the decreased expression of NDRG2 or the increased expression of CD24 is an important feature of lung adenocarcinoma. A combined detection of NDRG2/CD24 co-expression may benefit us in prediction of the prognosis of lung adenocarcinoma.     

Increased FAT10 expression is related to poor prognosis in pancreatic ductal adenocarcinoma

It has been reported that FAT10 plays an important role in cell proliferation. Their activity is increased in malignant cells compared to benign cells. However, the clinical and functional significance of FAT10 expression has not been characterized previously in pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to assess FAT10 expression and to explore its contribution to PDAC. Real-time quantitative PCR was performed to examine FAT10 expression in 38 pairs of fresh frozen PDAC tissues and corresponding noncancerous tissues. Using immunohistochemistry, we performed a retrospective study of the FAT10 expression levels on 134 archival PDAC paraffin-embedded samples. The relationship between FAT10 mRNA expression and clinicopathological features was analyzed by appropriate statistics. Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between FAT10 expression and prognosis of PDAC patients. The relative mRNA expression of FAT10 was significantly higher in PDAC tissues than in adjacent noncancerous tissues (P?<?0.001). By immunohistochemistry, the data revealed that high FAT10 expression was significantly correlated with clinical stage (P?<?0.001), histological differentiation (P?=?0.004), and lymph node metastasis (P?=?0.013). Consistent with these results, we found that high expression of FAT10 was significantly correlated with poor survival in PDAC patients (P?<?0.001). Furthermore, Cox regression analyses showed that FAT10 expression was an independent predictor of overall survival. In conclusion, this study confirmed the overexpression of FAT10 and its association with tumor progression in PDAC. It also provided the first evidence that FAT10 expression in PDAC was an independent prognostic factor of patients, which might be a potential diagnostic and therapeutic target of PDAC.     

Expression of BAMBI and its combination with Smad7 correlates with tumor invasion and poor prognosis in gastric cancer

Bone morphogenetic proteins and activin membrane-bound inhibitor (BAMBI) and drosophila mothers against decapentaplegic protein 7 (Smad7) are known to negatively regulate the transforming growth factor-β (TGF-β) signaling and play an important role in the progression of many malignant tumors. However, it remains unclear whether expression of BAMBI alone or in combination with Smad7 is associated with the progression of gastric cancer. In the present study, we investigated the expression of BAMBI and Smad7 in 276 cancer tissues and 263 tumor-adjacent tissues from gastric cancer patients, using tissue-microarray-based immunohistochemistry. The expression of BAMBI and Smad7 was significantly higher in cancer tissues than in tumor-adjacent tissues. The expression of BAMBI was significantly correlated with increased depth of invasion (P?=?0.010), lymphatic invasion (P?<?0.001), lymph node metastasis (P?=?0.001), TNM stage (P?=?0.008), and decreased differentiation (P?=?0.046). The expression of BAMBI was associated with a significantly shorter overall survival (OS) (P?=?0.006) and disease-free survival (DFS) (P?=?0.011). The combined expression of BAMBI and Smad7 was associated with more invasion and metastasis as well as less survival time in gastric cancer patients. The univariate analysis showed that the expression of BAMBI alone or in combination with Smad7 was significantly associated with the OS and DFS. These findings suggest that BAMBI and Smad7 may cooperatively inhibit the TGF-β signaling, and thus promote the progression of gastric cancer.     

RHBDD2: a 5-fluorouracil responsive gene overexpressed in the advanced stages of colorectal cancer

In previous studies, we identified rhomboid domain containing 2 (RHBDD2) gene to be markedly overexpressed in breast cancer patients that developed recurrence of the disease. In this study, we evaluated for the first time RHBDD2 gene expression in colorectal cancer (CRC). Five public available DNA microarray studies were compiled in a homogeneous dataset of 906 colorectal samples. The statistical analysis of these data showed a significant increase of RHBDD2 expression in the advanced stages of CRC (p?<?0.01). We validated these findings by immunohistochemistry on 130 colorectal tissue samples; RHBDD2 protein overexpression was also observed in the advanced stages of the disease (p?<?0.001). In addition, we investigated RHBDD2 expression in response to the chemotherapy agent 5-fluorouracile (5FU). We detected a significant increase of RHBDD2 mRNA and protein after 5FU treatment (20?C40???M; p?<?0.001). Overall, these results showed that RHBDD2 overexpression might play a role in colorectal cancer progression.     

Concomitant upregulation of nucleostemin and downregulation of Sox2 and Klf4 in gastric adenocarcinoma

Nucleostemin (NS) is a nucleolar protein involved in stem cell (SC) self-renewal by controlling cell cycle progression. In addition to SCs, NS is also expressed in some highly proliferating cells including several adult stem cells and cancer cell lines. NS knock-down in different cell lines demonstrated its cell type-dependent function in arresting cell cycle in either G1 or G2/M phases. Here, we have evaluated the expression of NS and iPS genes in 36 gastric cancer and their matched marginal nontumor tissues by means of real-time polymerase chain reaction (RT-PCR). We have also examined a potential causative role of NS in gastric tumorigenesis by suppressing its expression in a gastric cancer cell line, AGS. Our data revealed that NS expression level is much higher in tumor tissues (p?=?0.046), especially in high-grade ones (p?<?0.001), whereas the expression of Klf4 and Sox2 is downregulated in tumor tissues compared to marginal nontumor samples (p?<?0.001). Furthermore, NS suppression in the AGS cell line caused some morphological alterations, a cell cycle arrest at G1 phase, and an upregulation of iPS genes: Nanog, Sox2, and Klf4. Based on our results, NS overexpression seems to have a causative role in gastric tumorigenesis and/or progression, and it could be considered as a potential tumor marker for diagnosis, molecular classification, and molecular therapy of gastric adenocarcinoma.     

The expression and clinical significance of CLIC1 and HSP27 in lung adenocarcinoma

The purpose of this research was to study the roles of chloride intracellular channel protein 1 (CLIC1) and heat shock protein 27 (HSP27) in the clinical pathology of lung adenocarcinoma and to explore whether the expression of CLIC1 and HSP27 can be used as independent factors for the prediction of recurrence and prognosis after radical resection of lung adenocarcinoma. One hundred and three paraffin sections of lung adenocarcinoma tissues were collected, and the expression of CLIC1 and HSP27 was detected in these tumors using immunohistochemistry. The correlation of the expression of these two proteins with clinicopathological parameters and prognosis was statistically analyzed. In the 103 samples, the expression of HSP27 and CLIC1 was strongly positive in 61 (59.2%) and 49 cases (47.6%), respectively. Statistical analysis showed that the expression level of HSP27 did not significantly correlate with the patient’s age, sex, degree of tumor differentiation, T staging of tumors, and TNM staging of tumors (p?>?0.05), whereas the expression of CLIC1 did significantly correlate with T staging of tumors (p?=?0.029). Univariate analysis indicated that the patient’s ECOG score, T staging, N staging, TNM staging, and CLIC1 expression correlated with prognosis (p?=?0.031, 0.001, 0.011, 0.013, and <0.001, respectively). Multivariate statistical analysis showed that age, T staging, and CLIC1 expression were independent associated factors for predicting the 5-year survival rate of patients (p?=?0.026, 0.004, and <0.001, respectively). Age, T staging, and CLIC1 expression significantly correlated with the overall survival of post-operative lung adenocarcinoma patients. CLIC1 may be closely associated with the occurrence and development of lung adenocarcinoma and may be used as an effective marker for predicting the prognosis of this disease.     

Overexpression of NEDD9 is Associated with Altered Expression of E-Cadherin, β-Catenin and N-Cadherin and Predictive of Poor Prognosis in non-Small Cell Lung Cancer

Neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) is overexpressed in multiple tumor types, where it is thought to regulate tumor cell metastasis and act as a trigger of the epithelial-mesenchymal transition (EMT). Loss of E-cadherin/β-catenin and upregulation of N-cadherin are hallmarks of the EMT. The expression and correlation of NEDD9 with E-cadherin, β-catenin and N-cadherin in lung cancer are poorly characterized. We examined NEDD9, E-cadherin, β-catenin and N-cadherin protein expression in 105 cases of non-small cell lung carcinoma (NSCLC), including 43 cases of squamous cell carcinoma and 62 cases of lung adenocarcinoma, and the corresponding normal lung tissues using immunohistochemistry. NEDD9 was overexpressed in 56.2 % (59/105) of the NSCLC samples compared to normal lung tissue. Overexpression of NEDD9 correlated with abnormal expression of E-cadherin, β-catenin and N-cadherin (P?<?0.001, P?=?0.008 and P?=?0.027, respectively). Additionally, overexpression of NEDD9 correlated positively with lymph node metastasis in NSCLC (Chi-square test; P?=?0.015). The mean overall survival of NSCLC patients overexpressing NEDD9 (39.10?±?6.49 months) was markedly shorter than patients with normal NEDD9 expression (56.67?±?7.44 months; Log-Rank, P?=?0.001). Moreover, for patients with adenocarcinoma or squarmous cell carcinoma, the survival is also dramatically poorer upon overexpression of NEDD9. In multivariate analysis, overexpression of NEDD9 (P?=?0.013) and TNM stage (P?=?0.001) were significant independent prognostic factors for overall survival in NSCLC. In conclusion, overexpression of NEDD9 correlates with altered expression of EMT markers, increased lymph node metastasis and poorer survival in lung cancer.     

Elevated expression of HMGB1 in squamous-cell carcinoma of the head and neck and its clinical significance

PurposeHMGB1 overexpression has been reported in a variety of human cancers. However, the role of HMGB1 in squamous-cell carcinoma of the head and neck (SCCHN) remains unclear. The aim of the present investigation was to analyse HMGB1 protein expression in both SCCHN tissue and cell levels and to assess its prognostic significance in SCCHN.MethodsHMGB1 protein expression in 103 primary SCCHN tissue specimens was analysed by immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Additionally, HMGB1 protein expression was evaluated in cell level by Western blotting.ResultsBy Western blotting analysis, all the 5 SCCHN cell lines overexpressed HMGB1 protein, whereas the non-transformed immortalised cell line NP-69 had relatively weak HMGB1 protein expression. Immunohistochemical staining revealed that HMGB1 protein was detected in 91 (91/103, 88.3%) primary tumour samples, but only in 7 (7/16, 43.75%) adjacent non-carcinoma samples (p < 0.001); moreover, HMGB1 overexpression was significantly associated with T classification (p = 0.001), clinical stage (p < 0.001), recurrence (p < 0.001) and lymph node metastasis (p < 0.001). Survival analysis demonstrated that high HMGB1 expression was significantly associated with shorter disease-free and overall survival (both p < 0.001), especially in late patients with SCCHN. When HMGB1 expression and lymph node status were combined, patients with HMGB1 overexpression/lymph node (+) had both poorer disease-free and overall survival than others (both p < 0.001). Multivariate analysis further demonstrated that HMGB1 was an independent prognostic factor for patients with SCCHN.ConclusionsHMGB1 protein may contribute to the malignant progression of SCCHN, and present as a novel prognostic marker and a potential therapeutic target for patients with SCCHN.     

Prognostic importance of RASSF2 expression in patients with gastric cancer who had undergone radical gastrectomy

Background

Although Ras-association domain family of gene 2 (RASSF2) has been shown to undergo promoter methylation at high frequency in some cancer types and in brain metastases, its clinical utility as a useful prognostic molecular marker remains unclear in gastric cancer.

Methods

Prognostic significance of RASSF2 expression was retrospectively analysed by immunohistochemically in 105 patients with gastric cancer who underwent curative gastrectomy.

Results

Low RASSF2 expression was detected in 58 (55 %) patients, whereas 47 patients (45 %) had high RASSF2 expression. Lymph node involvement, pT stage, TNM stage, vascular invasion, perineural invasion and the presence of recurrence were found to be significantly related to RASSF2 expression levels. Low PRL-3 expression was closely correlated with lymph node metastasis (p = 0.001), advanced pT stage (p = 0.021), advanced TNM stage (p < 0.001), the presence of vascular invasion (p < 0.001), perineural invasion (p = 0.018) and high prevalence of recurrence (p = 0.003) compared with high RASSF2 expression. The median disease-free survival (DFS) time for patients with low RASSF2 expression was significantly worse than that of patients with high RASSF2 expression (10.2 vs. 50.6 months, p < 0.001). In addition, patients with high RASSF2 expression had the higher overall survival (OS) interval compared to patients with low RASSF2 expression (NR vs. 14.9 months, p < 0.001). In the multivariate analysis, the rate of RASSF2 expression levels was an independent prognostic factor, for DFS [p < 0.001, HR 0.12 (0.10–0.88)] and OS [p < 0.001, HR 0.10 (0.04–0.46)], as were pT stage and TNM stage, respectively.

Conclusions

RASSF2 may be an important molecular marker for carcinogenesis, prognosis and progression in gastric cancer, but the potential value of RASSF2 expression as a useful molecular marker in gastric cancer progression should be evaluated, comprehensively. It would be possible to develop treatments targeting RASSF2 and advance new treatment strategies for gastric cancer.

     

Combined evaluation of the expression of NUCKS and Ki-67 proteins as independent prognostic factors for patients with gastric adenocarcinoma

Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) has been recently documented in various malignancies. However, data regarding the expression and prognostic value of NUCKS in gastric adenocarcinoma are limited. Specimens from 159 gastric adenocarcinoma patients who underwent primary gastrectomy were collected. Immunohistochemical method was used to evaluate NUCKS and Ki-67 expression. The correlations between NUCKS and clinical significance were analyzed. Elevated NUCKS expression was significantly associated with TNM stage (P?=?0.034), depth of invasion (P?=?0.001), and expression of Ki-67 (P?=?0.035). Kaplan–Meier analysis indicated that NUCKS overexpression alone (P?=?0.045 for overall survival) or in combination with Ki-67 (P?=?0.007 for disease-free survival, P?=?0.002 for overall survival) was correlated with adverse prognosis of the patients. Multivariate analysis revealed that combined NUCKS and Ki-67 overexpression was an independent prognostic factor for both disease-free survival (hazard ratio?=?1.623, P?=?0.02) and overall survival (hazard ratio?=?1.667, P?=?0.016) in gastric adenocarcinoma patients. The combination of NUCKS and Ki-67 overexpression in gastric adenocarcinoma further distinguished a subgroup of patients with poor prognosis.     

Overexpression of G6PD is associated with poor clinical outcome in gastric cancer

This study aims to investigate the expression and significance of glucose-6-phosphate dehydrogenase (G6PD) in human gastric cancer progression and prognosis. Using immunohistochemistry and real-time RT-PCR assay, we identified abnormally elevated expression of G6PD in gastric cancer tissues compared to paired normal stomach mucosa tissues in 24 patients (p < 0.05). In order to investigate the correlations between G6PD and the clinicopathological features of gastric cancer, the expression of G6PD in 167 patients with gastric cancer were detected by immunohistochemistry, and the results showed that overexpression of G6PD was associated with the size of tumor (p = 0.039), depth of invasion (p = 0.039), lymph node metastasis (p = 0.044), distant metastasis (p = 0.003), TNM stage (p = 0.030), and survival rate (p = 0.010). Further, Cox multivariates analysis indicated that G6PD expression level was an independent prognostic factor for patients after radical resection (p = 0.013). In conclusion, overexpression of G6PD is closely related to progression of gastric cancer, and might be regarded as an independent predictor of poor prognosis for gastric cancer.     

Correlation of TNFAIP8 overexpression with the proliferation,metastasis, and disease-free survival in endometrial cancer

Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) is an apoptosis regulator proven to have an important function in the proliferation, invasion, metastasis, and progression of malignancies. In this study, we investigated the clinical role of TNFAIP8 overexpression in endometrial cancer (EC) and determined the relationship of TNFAIP8 with the proliferative antigen Ki-67 and metastasis-related gene matrix metallopeptidase 9 (MMP9) in 225 tumor specimens by immunohistochemistry and western blot, in order to elucidate more information on the role of TNFAIP8 protein with regard to the pathogenesis of EC. An association was observed between TNFAIP8 overexpression and clinicopathologic factors, such as advanced International Federation of Gynecology and Obstetrics stage (P?<?0.001), higher histologic grade (P?=?0.017), deep myometrial invasion (P?=?0.030), lymphovascular space invasion (P?=?0.011), lymph node metastasis (P?<?0.001), and recurrence. Furthermore, TNFAIP8 overexpression was strongly correlated with MMP9 and Ki-67 expression in the progression of ECs. Patients with high expression of TNFAIP8 (P?<?0.001 for both) and Ki-67 (P?=?0.007 and P?=?0.008) had poor overall survival and disease-free survival (DFS) rates. MMP9 overexpression did not affect survival outcomes (P?>?0.05). Multivariate Cox regression analysis revealed that TNFAIP8 (P?=?0.029) and lymph node metastasis (P?=?0.022) were independent factors of DFS in patients with EC. These findings suggested that TNFAIP8 may be used as a prognostic marker for the recurrence of EC, and its promotion of the proliferation and metastasis in EC may be due to its mediation of Ki-67 and MMP9.     

Differential expression of Pim-3, c-Myc,and p-p27 proteins in adenocarcinomas of the gastric cardia and distal stomach

Gastric cardia adenocarcinoma (GCA) is distinct from adenocarcinoma of the distal stomach because of its different etiological factors, tumor characteristics, and biological behavior. However, its pathogenesis is not fully understood. The purpose of this study is to characterize the role of Pim-3, c-Myc, and p-p27 in the tumorigenesis and progression of different sites of gastric adenocarcinoma by determining its pathogenetic significance. The expression of Pim-3, c-Myc, and p-p27 proteins was evaluated by immunohistochemistry in 140 resection specimens of gastric adenocarcinomas (78 GCAs , 62 DGAs and 20 normal gastric tissues). The level of expression of Pim-3, c-Myc, and p-p27 and the co-expression of all three markers (Pim-3+/c-Myc+/p-p27+) in GCA were significantly lower than that in DGA tumors (P?<?0.05). Detailed analysis of the immunoreactivity patterns showed that in DGA, Pim-3 immunoreactivity was associated significantly with poor tumor differentiation, advanced tumor stage, and presence of lymph node metastasis. In addition, c-Myc overexpression correlated with tumor stage and lymph node metastasis, and positive p-p27 expression correlated with poor differentiation and tumor stage. The phenotype of Pim-3⁺/c-Myc⁺/p-p27⁺ co-expression was closely correlated with tumor stage and lymph node metastasis (P?<?0.05). In contrast, GCA only demonstrated a close correlation of Pim-3 overexpression with poor tumor differentiation and tumor stage (P?<?0.05). Our results demonstrate the presence of different expression patterns of Pim-3, c-Myc, p-p27, and Pim-3⁺/c-Myc⁺/p-p27⁺ and their clinicopathologic significance in GCA and DGA tumors. Our results add support to the notion that distinct molecular mechanisms may be involved in the development and progression of adenocarcinomas from the gastric cardia and distal portion of stomach.     

Metastasis-associated protein 1 as a new prognostic marker for solid tumors: a meta-analysis of cohort studies

Metastasis-associated protein 1 (MTA1) is a molecular marker in various solid tumors that has recently been investigated. The prognostic significance of MAT1 expression remains controversial. In this work, we aimed to determine the relationship between immunohistochemistry-detected MAT1 expression and survival of patients with solid tumors by conducting a meta-analysis of cohort studies. Relevant studies were identified via an electronic database search updated on October 28, 2013. We included cohort studies that reported hazard ratios (HRs) or odds ratios (ORs) with 95 % confidence intervals (CIs) to determine the association of high MTA1 expression with overall survival (OS) and clinicopathological characteristics. Heterogeneity was quantified using I ² statistics, and publication bias was evaluated using funnel plots. Sensitivity analysis was conducted to evaluate the robustness of meta-analysis findings. We identified 16 cohort studies that focused on MTA1 overexpression and prognosis involving 2,253 cancer patients. Overall, the combined HR for OS was 1.85 (95 % CI: 1.55–2.28, P?<?0.001). Omission of any single study had no significant effect on the pooled HR estimate. When the studies were stratified by tumor type, similar results of poor prognosis were observed in non-small cell lung cancer (HR?=?2.05, 95 % CI: 1.14–3.68, P?=?0.016) and esophageal squamous cell carcinoma (HR?=?1.86, 95 % CI: 1.44–2.39, P?<?0.001). Moreover, multivariate survival analysis showed that MTA1 overexpression was an independent predictor of poor prognosis (HR?=?1.90, 95 % CI: 1.53–2.37, P?<?0.001). In addtional, MTA1 overexpression was significantly associated with tumor size (OR?=?2.72, 95 % CI?=?1.44–5.14, P?=?0.002), tumor stage (OR?=?2.44, 95 % CI?=?1.67–3.57, P?<?0.001), depth of invasion (OR?=?2.63, 95 % CI?=?1.74–3.97, P?<?0.001), and lymph node metastasis (OR?=?2.57, 95 % CI?=?1.57–4.19, P?<?0.001). However, when age, sex, and tumor differentiation were considered, no obvious association was observed. This study provides a comprehensive examination of the literature available on the association of MTA1 overexpression with OS and some clinicopathological features in solid tumors. Meta-analysis results provide evidence that MTA1 may be a new indicator of poor cancer prognosis. Considering the limitations of the eligible studies, other large-scale prospective trials must be conducted to clarify the prognostic value of MTA1 in predicting cancer survival.