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.     

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.     

Overexpression and cytoplasmic accumulation of Hepl is associated with clinicopathological parameters and poor prognosis in non-small cell lung cancer

Hepl, first described in 2008, is the fourth member of the Crk-associated substrate (CAS) family and is specifically expressed in the lung. Compared to other CAS proteins, Hepl has a varying effect on cell migration in different cell types. We speculated that Hepl may play a role in lung cancer invasion and metastasis. We quantified the expression and subcellular localization of Hepl in 143 non-small cell lung cancer (NSCLC) tissues, adjacent noncancerous tissues, and eight lung cancer cell lines using Western blotting, immunohistochemistry, and immunofluorescent staining. Expression of Hepl was correlated with the clinicopathological features of NSCLC. Hepl was overexpressed in 72.3 % (103/143) of the NSCLC tissues, compared to the adjacent noncancerous lung tissues (P?=?0.022). Overexpression of Hepl was associated with lymph node metastasis and high TNM stage (P?=?0.005 and P?=?0.045, respectively). Kaplan–Meier survival curves and the log-rank test indicated that overexpression of Hepl correlated with poorer overall survival in NSCLC (P?<?0.001), and Cox regression analysis demonstrated that overexpression of Hepl was an independent prognostic factor in NSCLC. Furthermore, cytoplasmic accumulation of Hepl was observed in a high metastatic potential lung cancer cell lines (H1299 and BE1), but not in low metastatic potential cell lines (LTE and A549). This study reveals that Hepl is overexpressed in the nucleus and aberrantly accumulates in the cytoplasm of NSCLC cells, and indicates that Hepl may play a role in the progression of lung cancer, including lymph node metastasis and TNM stage. Additionally, Hepl may be a useful prognostic factor in lung cancer.     

Expression of CHD1L in bladder cancer and its influence on prognosis and survival

Chromodomain helicase/ATPase DNA-binding protein 1-like (CHD1L) is overexpressed and highly associated with poor prognosis in many malignancies. However, the role of CHD1L in bladder cancer (BC) has not been thoroughly elucidated. The aim of this study is to investigate the relationship of CHD1L expression with clinicopathological parameters and prognosis in BC. Immunohistochemistry was carried out to investigate the protein expression of CHD1L in 153 BC tissues and 87 adjacent noncancerous tissues. Our data found that CHD1L protein expression was significantly higher in BC tissues than in adjacent noncancerous tissues (P?<?0.001). CHD1L overexpression was significantly correlated with histologic grade (P?=?0.005) and tumor stage (P?=?0.009). The Kaplan–Meier survival analysis revealed that survival time of patients with high CHD1L expression was significantly shorter than that with low CHD1L expression. Multivariate analysis further demonstrated that CHD1L was an independent prognostic factor for patients with BC. In conclusion, CHD1L is likely to be a valuable marker for carcinogenesis and progression of BC. It might be used as an important diagnostic and prognostic marker for BC 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.     

Neuropilin-1 is overexpressed in osteosarcoma and contributes to tumor progression and poor prognosis

Aim

Neuropilin (NRP)-1, a co-receptor for vascular endothelial growth factor (VEGF), plays an important role in angiogenesis and malignant progression of many cancers. However, the involvement of NRP-1 in osteosarcoma is not completely understood. The aim of this study was to investigate the expression pattern and clinical significance of NRP-1 in human osteosarcoma.

Methods

NRP-1 mRNA and protein expression levels were detected by RT-PCR and Western blot assays, respectively, using 166 pairs of osteosarcoma and noncancerous bone tissues. Then, the association of NRP-1 expression with clinicopathological factors or survival of osteosarcoma patients was further evaluated.

Results

RT-PCR and Western blot assays revealed that NRP-1 expression in osteosarcoma tissues was significantly higher than that in corresponding noncancerous bone tissues at both mRNA and protein levels (both P < 0.001). In addition, high NRP-1 expression more frequently occurred in osteosarcoma tissues with advanced clinical stage (P = 0.006), positive distant metastasis (P = 0.01) and poor response to chemotherapy (P = 0.006). Moreover, osteosarcoma patients with high NRP-1 expression had significantly shorter overall survival and disease-free survival (both P < 0.001) when compared with patients with the low expression of NRP-1. On Cox multivariate analysis, NRP-1 overexpression was an independent and significant prognostic factor to predict poor overall survival and disease-free survival (both P = 0.001).

Conclusion

This is the first study to reveal that NRP-1 overexpression may be related to the prediction of metastasis potency, response to chemotherapy and poor prognosis for osteosarcoma patients, suggesting that NRP-1 may serve as a prognostic marker for the optimization of clinical treatments.     

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.     

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.     

基于肿瘤数据库分析IGFBP5基因在结直肠癌中的表达及意义

目的研究IGFBP5基因在结直肠癌中的表达水平及临床意义,探讨IGFBP5在结直肠癌发生发展中的作用及其分子机制。方法使用RT-qPCR实验检测IGFBP5在结直肠癌组织和癌旁组织中的表达水平;分别从GEPIA2和Linked Omics数据库分析IGFBP5在结直肠癌组织中的表达与临床病理参数之间的相关性和对预后的影响;使用Linked Omics数据库导出结直肠癌中与IGFBP5相关的前1000位相关基因,并使用DAVID网站分析IGFBP5的分子功能和相关信号通路;使用STRING网站和Cytoscape软件预测与其可能与IGFBP5发生相互作用的蛋白网络。结果RT-qPCR结果显示:IGFBP5基因在结直肠癌组织中表达水平显著性升高(P<0.05);IGFBP5表达水平与结直肠癌N分期呈正相关(P<0.05),而与结直肠癌病理分级、T分期和M分期均无显著相关性(P均>0.05);IGFBP5表达水平越高,患者的总生存期和无病生存期越差(P均<0.05);GO分析结果显示:IGFBP5在结直肠癌中与细胞黏附、血管生成和血管内皮生长因子等多种促癌功能有关(P均<0.05);KEGG分析结果显示:IGFBP5基因与PI3K-Akt信号通路激活有关(P均<0.05);蛋白互作网络图结果显示:在结直肠癌中IGF1、IGF2、SPP1、LTBP1和FAM20C基因与IGFBP5基因关联最紧密。结论IGFBP5基因在结直肠癌组织中表达水平升高,并且IGFBP5的表达与结直肠癌淋巴结转移正相关,与临床预后负相关,因此IGFBP5可作为结直肠癌初步诊断和判断预后的标志物。     

Expression of APC, β-catenin and E-cadherin in Tunisian patients with gastric adenocarcinoma: clinical significance

Aberrant activation of the Wnt signalling pathway is a key feature of many cancers. β-Catenin, adenomatous polyposis coli (APC) and E-cadherin are major players in this pathway. The aim of this study is to examine the expression of β-catenin, APC and E-cadherin in tumour tissues of 80 Tunisian patients with gastric carcinoma and to determine the methylation status of the APC promoter in tumour tissues. Associations between protein expression and clinico-pathological parameters, including prognosis, were performed. Positive expression of β-catenin, APC and E-cadherin was observed in 77.5, 68.7 and 60 % of cases, respectively. Tumours lacking membranous expression of β-catenin had greater extent of lymph node metastasis, poor differentiation and advanced T-stage. The expression of E-cadherin correlated with poor differentiation (P?=?0.05) and β-catenin expression (P?=?0.004). With regards to prognosis, the overall survival time was significantly prolonged for patients showing normal β-catenin expression (exclusively or predominantly membranous staining) alone or combined with positive APC expression (P log rank?=?0.008 and 0.003, respectively). The methylated pattern of APC promoter 1A was detected in 43.8 % of cases and correlated with T-stage (P?=?0.046) and distant metastasis (P?=?0.037). No correlation was found between the methylated profile of APC promoter 1A and the expression of APC protein in tumour tissues. Our findings suggest that deregulation of the Wnt pathway via abnormal expression of β-catenin and E-cadherin occurred frequently in gastric carcinoma and correlated with worse clinical behaviour.     

Overexpression of CPE-ΔN predicts poor prognosis in colorectal cancer patients

Carboxypeptidase E (CPE) is one of the most important carboxypeptidases involved in biosynthesis of numerous peptide hormones and neurotransmitters and has an important role in endocrine regulation. A splice variant of CPE (CPE-ΔN) has been detected and the mechanism of CPE-ΔN action in tumorigenesis has been studied in many different cancers. The aim of this study was to examine CPE-ΔN expression in human colorectal cancer (CRC) and to evaluate its possible use as a potential prognostic marker. Two hundred nineteen primary colorectal tumors and corresponding normal tissues were included in the study. We have analyzed CPE-ΔN isoform expression by qRT-PCR and Western blot in 219 CRC patients. Correlations between CPE-ΔN mRNA expression and clinicopathological variables were determined with chi-square tests. Survival probabilities were determined using Kaplan–Meier analysis, and univariate and multivariate analyses of the prognostic factors were performed with a Cox regression model. Our results show that CPE-ΔN is overexpressed in colorectal tumor tissue and that high CPE-ΔN mRNA expression is closely correlated with tumor differentiation, pT classification, pN classification, tumor recurrence, and lymph node metastasis (P?=?0.042, 0.036, 0.031, 0.006, and 0.008, respectively). However, no correlation was observed between CPE-ΔN expression and age, gender, tumor localization, gross features, and the tumor size. In addition, patients with high CPE-ΔN expression had a significantly shorter survival (P?<?0.001, logrank test). Tumor differentiation, gross feature, pT classification, pN classification, tumor recurrence, lymph node metastasis, and CPE-ΔN status were significantly associated with poor prognosis after performing a univariate Cox survival analysis. High CPE-ΔN expression was also identified as an independent prognostic factor using a multivariate analysis (P?=?0.011). Based on these results, we can conclude that CPE-ΔN expression might be a potential prognostic marker for colorectal cancer patients.     

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.     

PLK4在结直肠癌中的表达及临床意义

背景与目的：Polo样蛋白激酶4（Polo-like kinases 4，PLK4）主要参与调控中心体的复制进程，过表达PLK4能够诱导肿瘤细胞中心体扩大、染色体不稳定及肿瘤侵袭性增强。该研究旨在探讨PLK4在人结直肠癌（colorectal cancer，CRC）中的表达及临床意义。方法：收集19例CRC组织及对应癌旁组织的新鲜标本，129例CRC组织及癌旁组织的石蜡标本。应用实时荧光定量聚合酶链反应（real-time fluorescent quantitative polymerase chain reaction，RTFQ-PCR）检测19例CRC组织及对应癌旁组织中PLK4 mRNA的表达；采用免疫组织化学法检测129例CRC患者手术切除石蜡标本的PLK4蛋白的水平，分析PLK4表达与CRC临床病理指标之间的相关性及与预后的相关性。结果：RTFQ-PCR显示，PLK4 mRNA表达在CRC组织中明显高于癌旁组织（P<0.01），免疫组织化学结果显示，PLK4蛋白阳性信号定位于细胞质及部分细胞核。PLK4蛋白在129例CRC组织中低表达62例，高表达67例，PLK4蛋白在CRC组织中的表达显著高于癌旁组织（P<0.01），PLK4蛋白水平与CRC分化程度（P=0.001 1）、N分期（P<0.000 1）、M分期（P=0.035 8）和TNM分期（P<0.000 1）呈正相关。Kaplan-Meier生存曲线显示，PLK4低表达组中位生存时间为27个月，高表达组中位生存时间为12个月，组间总生存率（overall survival，OS）差异有统计学意义，PLK4高表达组OS明显低于PLK4低表达组（P<0.000 1）。多因素COX比例风险模型分析显示，PLK4高表达不是CRC的独立预后因素（P=0.176）。结论：PLK4在CRC组织中高表达，并且与CRC组织分化差、淋巴结转移、远处转移及TNM分期相关；PLK4高表达提示CRC预后差，但不是独立预后因素。     

Clinicopathological and prognostic significance of myofibrillogenesis regulator-1 protein expression in pancreatic ductal adenocarcinoma

Myofibrillogenesis regulator-1 (MR-1) expression was detected in different malignancies and is associated with poor prognosis. However, its role in pancreatic ductal adenocarcinoma (PDAC) has not been fully elucidated. Thus, the aim of this study was to investigate the association of MR-1 expression with clinicopathologic features and prognosis in patients with PDAC. Immunohistochemistry was performed to investigate the protein expression of MR-1 and epithelial (E)-cadherin in 87 patients with PDAC. Results showed that MR-1 expression was correlated with histologic grade, tumor stage, and lymph node metastasis (all P <0.05). In addition, MR-1 expression showed a significant inverse correlation with E-cadherin expression (P?=?0.002). Furthermore, the variables associated with prognosis were analyzed by Cox’s proportional hazards model. Kaplan–Meier analysis was used to plot survival curves according to different expression levels of MR-1. Kaplan–Meier analysis revealed that MR-1 expression was significantly associated with worse disease-free survival (DFS) and overall survival (OS) rates in patients with PDAC (both P <0.001). Finally, multivariate analysis demonstrated that MR-1 expression, together with histologic grade, tumor stage, lymph node metastasis, was an independent prognostic factor for both DFS and OS rates in patients with PDAC. MR-1 overexpression was tightly associated with more aggressive tumor behavior and a poor prognosis, indicating that MR-1 is a valuable molecular biomarker for PDAC progression.