CHD1L is a novel independent prognostic factor for gastric cancer

Background

Chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) is involved in malignancies. However, the role of CHD1L in gastric cancer (GC) has not been elucidated. The aim of this study is to explore the clinical role of CHD1L in GC.

Methods

The gene and protein expression levels of CHD1L were detected by quantitative real-time PCR and Western blot analysis in fresh samples of GC and paired adjacent noncancerous tissue (n = 34). We evaluated the CHD1L expression by immunohistochemistry in a large number of GC patients (n = 616) and paired adjacent noncancerous tissues from December 1, 2004 to December 1, 2008. The correlations of CHD1L expression with clinicopathological features and clinical outcome were analyzed.

Results

The gene and protein expression levels of CHD1L were higher in fresh samples of GC than in paired adjacent noncancerous tissues as determined by quantitative real-time PCR and Western blot analysis. Immunohistochemical analysis showed that positive expression rates of CHD1L in GC and paired adjacent noncancerous tissues were 58.7 % (361/616) and 7.3 % (45/616), respectively. CHD1L positivity was significantly associated with clinical stage and distant metastasis. GC patients with positive CHD1L expression had shorter overall survival than those with negative CHD1L expression. Multivariate analysis showed that CHD1L was an independent prognostic marker for overall survival [Hazard Ratio (HR) = 5.952, 95 % confidence interval (CI) = 3.194–11.187, P = 0.0043].

Conclusion

These results indicated that CHD1L could serve as a prognostic marker for GC.     

Expression of NEDD9 in pancreatic ductal adenocarcinoma and its clinical significance

The aim of this study was to investigate the expression and prognostic significance of NEDD9 in pancreatic ductal adenocarcinoma (PDA). Expressional levels of NEDD9 mRNA and protein in paired pancreatic cancer lesions and adjacent noncancerous tissues were examined by quantitative real-time PCR and western blotting. NEDD9 expression was analyzed by immunohistochemistry in 106 patients with PDA. The correlations between NEDD9 immunostaining levels and clinicopathologic factors, as well as the follow-up data of patients, were analyzed statistically. NEDD9 protein and mRNA levels were elevated in pancreatic carcinoma lesions compared with the paired adjacent noncancerous tissues. A high level of expression of NEDD9 was significantly correlated with clinical staging (P?<?0.001), lymph node metastasis (P?<?0.001), and histological differentiation (P?<?0.001). Patients with a higher NEDD9 expression had a significantly shorter survival time than those patients with lower NEDD9 expression. The multivariate analysis revealed that NEDD9 could serve as an independent factor of poor prognosis. Our finding indicates that NEDD9 could be used as prognostic molecular marker and therapeutic target for PDA.     

Evaluating the expression of CARMA3 as a prognostic tumor marker in renal cell carcinoma

Increased expression of CARMA3 has been reported to be involved in tumorigenesis and tumor progression of several cancer types. The aim of our study is to investigate the prognostic role of CARMA3 expression in patients with renal cell carcinoma (RCC). Real-time quantitative PCR was performed to detect CARMA3 mRNA expression level in 31 paired samples of RCC and adjacent noncancerous renal tissues. Subsequently, extensive immunohistochemistry was performed to detect CARMA3 protein expression in 114 RCC cases. Clinicopathological data for these patients were evaluated. The prognostic significance was assessed using the Kaplan–Meier survival estimates and log-rank tests. CARMA3 mRNA expression was significantly higher in RCC tissues compared with adjacent noncancerous renal tissues (3.525?±?1.233 vs. 1.512?±?0.784, P?<?0.001). In addition, high CARMA3 expression in RCC tissues was significantly associated with tumor size (P?=?0.026), histological differentiation (P?=?0.039), tumor stage (P?=?0.006), and the presence of metastasis (P?<?0.001). Moreover, Kaplan–Meier analysis showed that patients with high CARMA3 expression also had a significantly poorer prognosis than those with low CARMA3 expression (log-rank test, P?<?0.001). Furthermore, multivariate analysis illustrated that CARMA3 overexpression might be an independent prognostic indicator for the survival of patients with RCC. In conclusion, this work shows that CARMA3 may serve as a novel and prognostic marker for RCC and play a role during the development and progression of the disease.     

Expression and clinical significance of STIP1 in papillary thyroid carcinoma

The aim of this study was to detect stress-induced phosphoprotein 1 (STIP1) expression in papillary thyroid carcinoma (PTC) and to analyze its association with prognosis of PTC patients. Immunohistochemistry was performed to detect the expression of STIP1 in 113 PTC tissues and paired adjacent noncancerous tissues. The χ2 test was used to analyze the relationship between STIP1 expression and clinicopathological characteristics. Survival curves were plotted by the Kaplan–Meier method and compared using the log-rank test. Survival data was evaluated using univariate and multivariate Cox regression analysis. We identified abnormally elevated expression of STIP1 protein in PTC tissues compared to paired adjacent noncancerous tissues. Clinicopathological analysis showed that STIP1 expression was significantly correlated with tumor size (P?=?0.017), lymph node metastasis (P?=?0.007), and TNM stage (P?=?0.026). Patients with higher STIP1 expression had shorter overall survival time, whereas those with lower STIP1 expression had longer survival time. Multivariate analysis suggested that STIP1 expression might be an independent prognostic indicator (P?<?0.05) for the survival of patients with PTC. In conclusion, our findings provide evidences that positive expression of STIP1 in PTC may be important in the acquisition of an aggressive phenotype, and it is an independent biomarker for poor prognosis of patients with PTC.     

Clinicopathological significance of SLP-2 overexpression in human gallbladder cancer

Several studies have indicated that overexpression of stomatin-like protein 2 (SLP-2) has been identified in several types of cancer. However, its role and clinical relevance in gallbladder cancer (GBC) is unknown. The purpose of this study was to reveal the prognostic significance of SLP-2 in GBC. The SLP-2 expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction (qRT-PCR), and immunohistochemistry in GBC tissues and adjacent noncancerous tissues. Statistical analyses were applied to test the associations between SLP-2 expression, clinicopathologic factors, and prognosis. Immunohistochemistry and qRT-PCR showed that the protein and mRNA expression levels of SLP-2 were both significantly higher in GBC tissues than in adjacent noncancerous tissues. In addition, immunohistochemistry analysis showed that SLP-2 expression was significantly correlated with histological grade (P <0.001), pathologic T stage (P?=?0.019), clinical stage (P?=?0.001), and lymph node metastasis (P?=?0.026). The Kaplan–Meier survival curves indicated that patients with high expression of SLP-2 had shorter overall survival than those with low expression (P <0.001). Meanwhile, the Cox multivariate analysis indicated that high expressions of SLP-2 were an independent prognostic factor for patients with GBC. These data showed that SLP-2 may play an important role in human GBC tumorigenesis, and SLP-2 might serve as a novel prognostic marker in human GBC.     

Aberrant TIG1 methylation associated with its decreased expression and clinicopathological significance in hepatocellular carcinoma

Recently, it has been reported that tazarotene-induced gene 1 (TIG1) methylation was frequently detected in a variety of human cancers. However, the relationship between the TIG1 methylation and the characteristics of hepatocellular carcinoma (HCC) remains unknown. The aim of present study was to observe the promoter methylation of TIG1 in HCC tissues and assess its prognostic significance for HCC. Real-time quantitative polymerase chain reaction and methylation-specific polymerase chain reaction were used, respectively, to examine the mRNA expression and methylation status of TIG1 in 91 pairs of HCC and adjacent noncancerous tissues. The mRNA expression level of TIG1 was significantly lower in HCC tissues than in adjacent noncancerous tissues. The rate of TIG1 promoter methylation was significantly higher in HCC tissues than in adjacent noncancerous tissues (P?<?0.001). A strong correlation between downregulation and promoter methylation was found in these tumors (P?<?0.001). More importantly, TIG1 methylation status was related to tumor size (P?=?0.015), histological differentiation (P?=?0.004), and tumor stage (P?<?0.001). Kaplan–Meier survival analysis showed that TIG1 promoter hypermethylation was associated with a worse outcome in patients with HCC. Further, Cox multivariate analysis indicated that TIG1 methylation status was an independent prognostic factor for the overall survival rate of HCC patients. In conclusion, our data suggested that epigenetic silencing of TIG1 gene expression by promoter hypermethylation may play an important role in HCC.     

Mitotic arrest deficient-like 1 is correlated with poor prognosis in small-cell lung cancer after surgical resection

Mitotic arrest deficient-like 1 (MAD1L1) whose dysfunction is associated with chromosomal instability plays a pathogenic role in a few human cancers. However, the status of MAD1L1 expression in small-cell lung cancer (SCLC) remains unknown. Immunohistochemistry was used to determine the expression of MAD1L1 protein in 32 lymph node metastasis (LN-M) tissues and 88 primary SCLCs compared with 32 adjacent noncancerous tissues. The associations of MAD1L1 protein expression with the clinicopathologic features and clinical outcomes in patients with SCLC were analyzed. The ratio of MAD1L1 positive expression was higher in primary SCLC tissues (39.8 %) and LN-M tissues (46.9 %) compared with adjacent noncancerous tissues (9.4 %). MAD1L1 positive expression was associated with tumor-node-metastasis (TNM) stage (P?=?0.003), International Association for the Study of Lung Cancer (IASLC) stage (P?=?0.004), tumor size (P?=?0.015), lymph node metastasis (P?=?0.014), and recurrence (P?<?0.001). Multivariate analysis suggested that MAD1L1 positive expression was an independent factor for overall survival (hazard ratio (HR) 2.002; 95 % confidence interval (CI) 1.065–3.763; P?=?0.031) and recurrence-free survival (HR 2.263; 95 % CI 1.197–4.276; P?=?0.012). To sum up, MAD1L1 positive expression may be associated with tumour progression and metastasis in SCLCs and may thus serve as a new biomarker for prognosis in these patients.     

Overexpression of MACC1 protein and its clinical implications in patients with glioma

Metastasis associated in colon cancer 1 (MACC1) has been regarded as a novel potential therapeutic target for multiple cancers. However, the impact of MACC1 in glioma remains unclear. The aim of this study was to analyze the correlation of MACC1 expression with the clinicopathological features of glioma. MACC1 mRNA and protein expression levels in human glioma tissues were detected by quantitative real-time polymerase chain reaction and immunohistochemistry assays, respectively. MACC1 mRNA and protein expression were both significantly higher in glioma tissues than in corresponding noncancerous brain tissues (both P?<?0.001). In addition, statistical analysis suggested that high MACC1 expression was significantly correlated with advanced pathological grade (P?=?0.004) and that patients with high expression of MACC1 protein exhibited a poorer prognosis than those with low MACC1 expression. Furthermore, Cox multivariate analysis showed that MACC1 overexpression was an independent prognostic factor for predicting the overall survival of glioma patients. In conclusion, expression of MACC1 in glioma could be adopted as a candidate biomarker for the diagnosis of clinical stage and for assessing prognosis, indicating for the first time that MACC1 may play an important role in the tumor development and progression in glioma. MACC1 might be considered as a novel therapeutic target against this cancer.     

Upregulation of the long noncoding RNA HOTAIR predicts recurrence in stage Ta/T1 bladder cancer

Stage Ta/T1 urothelial carcinoma of the bladder (Ta/T1 BC) has a marked tendency to recurrence. Long noncoding RNA HOTAIR has been reported to be expressed in some human cancers such as breast cancer, and it may be positively correlated with patient’s prognosis. The aim of our study was to evaluate the prognostic value of HOTAIR in Ta/T1 BC. HOTAIR expression in Ta/T1 BC tissues and adjacent normal tissues was collected from 110 patients and measured by real-time quantitative PCR. The relationships between HOTAIR and the clinical pathological characteristics of Ta/T1 BC patients were analyzed. Immunohistochemistry was done to detect the protein of Wnt inhibitory factor 1 (WIF-1) as well. Ninety out of 110 specimens were detected in HOTAIR high expression. Histological grade and expression levels of HOTAIR were positively correlated with the recurrence rate. HOTAIR expression (hazard ratio 4.712; 95 % CI 2.894–8.714; P?相似文献   

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.     

Prognostic significance of USP22 as an oncogene in papillary thyroid carcinoma

Ubiquitin-specific protease 22 (USP22), a novel deubiquitinating enzyme, has been associated with metastasis, therapy resistance, and cell cycle progression. The purpose of this study was to investigate the expression level of USP22 in papillary thyroid carcinoma (PTC) samples and to evaluate its clinical significance in PTC patients. USP22 expression was examined in 30 fresh PTC tissues and paired adjacent noncancerous tissues by real-time quantitative RT-PCR. Immunohistochemistry for USP22 was performed on additional 156 PTC tissues. The clinical significance of USP22 expression was analyzed. We found that the expression levels of USP22 mRNA and protein in PTC tissues were both significantly higher than those in noncancerous tissues. Clinicopathological analysis showed that USP22 expression was significantly correlated with tumor size (p?=?0.036), extracapsular invasion (p?=?0.012), multifocality (p?=?0.014), lymph node metastasis (p?=?0.022), distant metastasis (p?=?0.005), and TNM stage (p?=?0.002). The Kaplan–Meier survival curves revealed that USP22 expression was associated with poor prognosis in PTC patients. USP22 expression was an independent prognostic marker of overall patient survival in a multivariate analysis. Our findings suggest that USP22 is an independent predictor of poor prognosis of PTC patients.