Overexpression of periostin is significantly correlated to the tumor angiogenesis and poor prognosis in patients with esophageal squamous cell carcinoma

Recent studies have found that periostin (PN), as a kind of secreted glycoprotein, is closely related to the metastatic potential and prognosis of many kinds of tumors. This study aimed to examine the expression of PN in patients with esophageal squamous cell carcinoma (ESCC) and explore the relationship of PN expression with clinicopathologic factors, tumor angiogenesis and prognosis. The results showed that increased PN protein expression was prevalent in ESCC and was significantly associated with lymphatic metastasis (P=0.008), tumor differentiation (P=0.04), venous invasion (P=0.014) and TNM stage (P=0.001). Additionally, expression of PN was found to be an independent prognostic factor in ESCC patients. High expression of PN protein is closely correlated to the tumor progression and angiogenesis and poor survival of ESCC. Taken together, PN is a promising biomarker to identify individuals with poor prognostic potential and concludes the possibility of its use as a prognostic marker in patients with ESCC.     

PINCH expression and its significance in esophageal squamous cell carcinoma

Particularly interesting new cysteine-histidine rich protein (PINCH), as a newly discovered protein of LIM family members, may play a role in signal transduction of integrin and growth factor, and involved in the incidence and development of tumors. PINCH protein is overexpressed in tumor-associated stroma of several types of tumors. However, there is no study of the PINCH in esophageal cancer, therefore we investigated PINCH expression in esophageal squamous cell carcinomas and its clinicopathological significance in the patients. PINCH expression was immunohistochemically examined in 20 normal esophageal samples and 64 esophageal squamous cell carcinomas. The results showed that PINCH expression in the stroma of cancers was heterogeneous, and its positive rate (56%) was higher than that of normal esophageal mucosa (5%, p<0.0001). The stronger staining was observed at the invasive edge of tumor when compared to the inner area of tumor. The rate of positive PINCH (90%) in the cases with lymph node metastasis was higher than that (41%) in the cases without metastasis (p<0.0001). PINCH expression was not correlated with patients' gender, age, tumor location, size and differentiation (p>0.05). The results suggest that PINCH protein may be a marker of tumor associated-stroma involving tumor development, and predicting the ability of invasion and metastasis of esophageal squamous cell carcinoma.     

Overexpression of long non-coding RNA UCA1 predicts a poor prognosis in patients with esophageal squamous cell carcinoma

Introduction: Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology, and the lncRNA UCA1 is upregulated in several cancers such as bladder cancer, breast cancer and colorectal cancer, however, the contributions of UCA1 to esophageal cancer remain largely unknown. Methods: Expression levels of lncRNA UCA1 in esophageal squamous cell carcinoma (ESCC) patients and esophageal cancer cell lines were evaluated by quantitative real-time PCR (qRT-PCR), and its association with overall survival of patients was analyzed by statistical analysis. Small interfering RNA was used to suppress UCA1 expression in esophageal cancer cell line. In vitro assays were conducted to further explore its underlying roles in tumor progression. Results: The relative level of UCA1 was significantly higher in ESCC tissues compared to the adjacent non-tumor tissues, and remarkably higher expression of UCA1 was found in esophageal cancer cell lines compared with the immortalized esophageal epithelial cell line NE1. The ESCC patients with higher UCA1 expression had an advanced clinical stage and a poorer prognosis than those with lower expression. In vitro assays, our data indicated that downregulation of UCA1 decrease cell proliferation, migration, and invasion ability. Conclusions: lncRNA UCA1 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target.     

A four actin-binding protein signature model for poor prognosis of patients with esophageal squamous cell carcinoma

The actin cytoskeleton is a dynamic structure with actin-binding proteins (ABPs) playing an essential role in the regulation of migration, differentiation and signal transduction in all eukaryotic cells. We examined the relationship between altered expression of four ABPs and clinical parameters in esophageal squamous cell carcinoma (ESCC). To this end, we analyzed 152 formalin-fixed and paraffin-embedded esophageal curative resection specimens by immunohistochemistry for tensin, profilin-1, villin-1 and talin. A molecular predictor model, based on the combined expression of the four proteins, was developed to correlate the expression pattern of the four ABPs with clinical factors and prognosis of ESCC. According to the results, weak significance was found for tensin in lymph node metastasis (P=0.033), and profilin-1 in pTNM stage (P=0.031). However, our four-protein model showed strong correlation with the 5-year overall survival rate (P=0.002). Similarly, Kendall’s tau-b test also showed the relationship between the collective expression pattern of the four ABPs with lymph node metastasis (P=0.005) and pTNM stage (P=0.001). Our results demonstrate that the collective protein expression pattern of four actin-binding proteins could be a biomarker to estimate the prognosis of ESCC patients.     

Microsatellite instability in esophageal squamous cell carcinoma is not associated with hMLH1 promoter hypermethylation

To test whether a subset of esophageal squamous cell carcinomas (SCC) develop through a deficiency in DNA mismatch repair, we examined microsatellite instability (MSI) using 11 microsatellite markers including BAT-26, hMLH1 protein expression by immunohistochemistry, and methylation status of the hMLH1 promoter by methylation-specific polymerase chain reaction (MSP). p53 mutations were also investigated. Microsatellite instability at one or more loci was observed in 40% (12/30) of esophageal SCC tumor samples, although only one of these tumors was categorized as high-frequency MSI (MSI-H) and none showed BAT-26 instability. While immunohistochemistry revealed decreased hMLH1 protein expression in 27% (8/30) of the tumors, hMLH1 promoter hypermethylation was not observed. Absence of hMLH1 protein expression was relatively common in well-differentiated (keratinizing-type) esophageal SCC, but was not associated with hMLH1 promoter hypermethylation. p53 mutation was detected in 37% (11/30) and loss of heterozygosity (LOH) in 90% (27/30) of esophageal SCC samples. Our results suggested that most esophageal SCC develop through defects in tumor suppressor genes (i.e. the suppressor pathway), and that MSI in esophageal SCC probably represent random replication errors rather than being associated with DNA mismatch repair deficiency.     

Association of nuclear annexin A1 with prognosis of patients with esophageal squamous cell carcinoma

Although recent progress has been made in the diagnosis and treatment of cancer, the prognosis of esophageal squamous cell carcinoma (ESCC) remains poor. The identification of biomarkers for ESCC prognosis is important for treatment decisions. The aim of this study was to evaluate the relationship between the expressions of Annexin A1 (ANXA1), three prime repair exonuclease 1 (TREX1) and apurinic/apyrimidinic endonuclease-1 (APE1) and clinical outcome of patients with ESCC. The expressions of ANXA1, TREX1 and APE1 in 93 pairs of ESCC and paracancerous tissues were tested using immunohistochemistry. ANX1, TREX1 and APE1 were dysregulated in ESCC. Nuclear expressions of ANXA1 and APE1 were significantly associated with pathologic type (P = 0.004 and 0.040, respectively). Patients with low expression of nuclear ANXA1 had a better prognosis than those with high expression of nuclear ANXA1 (HR = 0. 448, 95% CI 0.236-0.849, P = 0.014), especially for those with histologic grade 1 and 2 (HR = 0.303, 95% CI: 0.155-0.593, P < 0.001). In conclusion, nuclear ANXA1 may be potentially used as a prognostic biomarker for ESCC.     

Human leukocyte antigen G is associated with esophageal squamous cell carcinoma progression and poor prognosis

Human leukocyte antigen G (HLA-G) is a non-classical HLA class I molecule thought to play a key role in maternal-fetal tolerance and cancer immune evasion. This study aimed to investigate the HLA-G expression in lesion sections and plasma sHLA-G levels of primary esophageal squamous cell carcinoma (ESCC) patients and its clinical significance in diagnosis and prognosis of ESCC. 60 ESCC patients and 28 healthy controls were recruited, and the positive expression of HLA-G in ESCC lesions and adjacent normal tissues were 70% (42/60) and 8.6% (5/60) (P < 0.05), respectively, while no expression was found in normal controls. HLA-G1 and HLA-G5 were determined to be dominating isoforms measured by RT-PCR. There was a significant difference in plasma sHLA-G levels between patients with ESCC (15.04 U/ml, range 4.33–250.00 U/ml) and healthy controls (6.81 U/ml, range 0–29.27 U/ml) (P < 0.01). The plasma IL-10 level was higher in ESCC patients than the controls (23.86 pg/ml vs. 12.81 pg/ml, P < 0.01). HLA-G expression in lesion tissues was correlated with cancer cell differentiation (P = 0.033), lymph node metastasis (P = 0.035) of ESCC. However, no obvious correlations were demonstrated between the plasma sHLA-G levels and the clinicopathological parameters. There was a significant correlation between sHLA-G and IL-10 expression (r = 0.353, P = 0.006) in patients with Esophageal squamous cell carcinoma. HLA-G positive expression showed poorer prognosis of ESCC. HLA-G positive expression might serve as a potential marker in the diagnosis or prediction of ESCC.     

ADAMTS-6 is a predictor of poor prognosis in patients with esophageal squamous cell carcinoma

Background

A disintegrin and metalloprotease with thrombospondin motif (ADAMTS) enzymes play important roles in cell functions including adhesion, invasion, migration, and proliferation. ADAMTS-6 is a member of the ADAMTS family; reports of its relationship with esophageal squamous cell carcinoma (ESCC) progression are rare. It is unclear whether ADAMTS-6 could be an independent ESCC biomarker.

Overexpression of FAM3C is associated with poor prognosis in oral squamous cell carcinoma

Expression of the family with sequence similarity 3 member C (FAM3C) is necessary for the epithelial-mesenchymal transition (EMT). However, the expression level and clinicopathological significance of FAM3C in oral squamous cell carcinoma (OSCC) has not been thoroughly elucidated to date. We performed immunohistochemical staining on human OSCC specimens with FAM3C, co-inhibitory immune checkpoints, EMT markers, and cancer stem cells (CSCs) markers to analyze the expression levels and clinicopathological features of FAM3C in OSCC. There were 210 primary OSCC specimens, 69 oral epithelial dysplasia and 42 normal oral mucosae in our human OSCC tissue microarrays cohort. We observed that FAM3C expression was upregulated in OSCC compared with normal mucosa and epithelial dysplasia (P?<? 0.001). Moreover, patients with higher FAM3C expression levels had a worse prognosis than those with lower expression levels (P < 0.05). Also, FAM3C expression was positively correlated with the immune checkpoints PD-L1, VISTA, and B7-H4, the EMT marker Slug and the CSC markers SOX2 and ALDH1. In conclusion, these findings suggested that overexpression of FAM3C in human OSCC may predict a poor prognosis for OSCC patients.     

FEZ1基因在食管癌变过程中的作用

目的探讨FEZ1基因在食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)组织中的表达及其与患者预后的关系。方法采用Western blot和免疫组化法分析FEZ1基因在ESCC中的表达情况,应用SPSS 13.0软件分析其与临床病理资料及预后的关系。结果 FEZ1蛋白阳性表达在食管癌中的表达与浸润深度、肿瘤大小相关(P<0.05);而与肿瘤组织分化程度、淋巴结转移无关(P>0.05)。正常食管组织中FEZ1的蛋白表达(4.3±0.39)明显高于食管癌组织中(1.6±0.25),且差异有显著性(P<0.05)。FEZ1的高表达提示患者的5年生存率高。结论 FEZ1基因在食管癌的发生、发展过程中起着重要的作用;FEZ1基因在食管癌中可能是候选的抑癌基因。     

Increased expression of metastasis-associated in colon cancer-1 in renal cell carcinoma is associated with poor prognosis

Metastasis-associated in colon cancer-1 (MACC1) expression in tumor specimens is an independent prognostic indicator of metastasis, which has recently gained considerable attention in cancer research, due to its overexpression in several types of carcinoma. However, MACC1 expression patterns and its possible role in renal cell carcinoma remain unknown. This study aimed to investigate MACC1 expression in renal cell carcinoma via immunohistochemical analysis and determine the relationship between MACC1 expression and cancer prognosis. Positive MACC1 expression was found to significantly correlate with distant metastasis and TNM stage (P < 0.05). A Kaplan-Meier survival analysis revealed that patients with higher MACC1 expression had a significantly lower disease-free rate (P < 0.05). These results indicate that MACC1 expression is significantly associated with prognosis in patients with renal cell carcinoma. To the best of our knowledge, this is the first study on the significance of MACC1 as a prognostic marker in renal cell carcinoma. MACC1 expression may be a useful target for the development of new therapeutic approaches, including molecular targeted therapeutic agents, for renal cell carcinoma.     

Association of Kruppel-like factor 4 expression with the prognosis of esophageal squamous cell carcinoma patients

Objective: To investigate the association of Kruppel-like factor 4 (KLF4) expressions with the prognosis of esophageal squamous cell carcinoma (SCC) patients. Methods: Ninety-eight cases of esophageal carcinoma patients were enrolled. The expression of KLF4 in the esophageal SCC and normal esophageal mucosa tissues were examined by immunohistochemistry. The correlations between the expression of KLF4 protein and patients’ clinical characteristics and prognosis were analyzed. Results: We observed higher expressed KLF4 in normal esophageal mucosa tissues than esophageal SCC tissues, with positive rate of 82.7% (81/98) and 43.8% (43/98) respectively. In patients with lymphatic metastasis, the positive rate of KLF4 was 24.4% (10/41), whereas it was 57.9% (33/57) in patients without lymphatic metastasis, and the difference was significant (x² = 10.871, P = 0.001). The positive rates of KLF4 were 62.5% (5/8), 53.1% (26/49) and 29.3% (12/41) in stage I, II and III patients, respectively. There were no correlations between the expression of KLF4 and gender, age, tumor size, location, differentiation grade and infiltration depth. The 5-year survival rates and median survival times were 48.8% and 25.5%, and 55 and 26 months for the patients with KLF4 positive and negative expression, respectively. There were significant differences between the patients with KLF4 positive expression and negative expression in the 5-year survival rates and median survival times (x² = 5.747 and 4.493, P = 0.017 and 0.034). Conclusion: KLF4 might act as a tumor suppressor in esophageal SCC and the expression status of KLF4 could be considered as a prognosis predictor for esophageal SCC patients.     

Up-regulation of miR-335 predicts a favorable prognosis in esophageal squamous cell carcinoma

Introduction: MicroRNAs (miRNAs) are noncoding RNAs that regulate multiple cellular processes during cancer progression. MiR-335 has recently been identified to be involved in tumorigenesis of several cancers such as ovarian cancer and gastric cancer. However, the regulation of miR-335 in esophageal squamous cell carcinoma (ESCC) has not been reported yet. Methods: Expression of miR-335 in tumor and their normal matched tissues was determined by quantitative real-time PCR in 67 ESCC patients and its association with overall survival of patients was analyzed by statistical analysis. Results: The expression level of miR-335 was reduced in malignant tissue samples in comparison to normal matched tissue (P < 0.05). It was also proved that miR-335 expression was associated with ESCC histological grade, lymph node metastasis, tumor stage and clinical stage (P < 0.05). In addition, the Kaplan-Meier survival curves revealed that low miR-335 expression was associated with poor prognosis in ESCC patients. Multivariate analysis showed that miR-335 expression was an independent prognostic marker of overall survival of ESCC patients. Conclusions: The study proves for the first time that miR-335 is down regulated in a majority of ESCC patients. Our results indicate that miR-335 expression is an independent prognostic factor for patients with esophageal cancer, which might be a potential valuable biomarker for ESCC.     

新疆地区口腔鳞状细胞癌中PLCE1蛋白的表达及临床意义

目的探讨PLCE1蛋白在新疆地区口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中的表达及预后价值。方法采用免疫组化EnVision两步法检测124例OSCC及63例癌旁正常组织中PLCE1蛋白的表达,分析其表达与OSCC临床病理特征及预后的关系。结果OSCC及癌旁组织中PLCE1蛋白高表达率分别为41.9%(52/124)和0(0/63),差异有统计学意义(P<0.0001)。PLCE1诊断OSCC的ROC曲线下面积(AUC)为0.954(敏感度83.9%,特异性95.2%)。Kaplan-Meier及Cox单因素分析显示,PLCE1高表达(P=0.004、P=0.006)和T分期(P=0.002、P=0.004)是影响患者不良预后的危险因素。Cox多因素分析结果显示,PLCE1高表达(P=0.008)和T分期(P=0.005)是患者预后的独立因素。结论PLCE1蛋白在新疆地区OSCC组织中高表达,且与患者不良预后相关,可作为肿瘤患者不良预后的新型生物标志物。