High BRCA2 mRNA expression predicts poor prognosis in breast cancer patients

The prognostic significance of BRCA2 mRNA levels in tumor tissues was studied in sporadic breast cancer patients. BRCA2 mRNA levels were determined by real-time PCR. Histologic grade III tumors showed significantly (p = 0.001) higher BRCA2 mRNA levels (0.828 +/- 0.102 BRCA2/beta-glucuronidase mRNA ratio, mean +/- SE) than histologic grade I and II tumors (0.438 +/- 0.055) and estrogen receptor (ER)-negative tumors (0.773 +/- 0.102) showed a nonsignificant (p = 0.072) trend toward an increase in BRCA2 mRNA levels compared to ER-positive tumors (0.541 +/- 0.079). Other clinicopathologic parameters, such as menopausal status, lymph node status and tumor size, were not significantly associated with BRCA2 mRNA levels. Patients with high BRCA2 mRNA levels showed a significantly (p = 0.006) lower 5-year disease free survival rate (63%) than those with low levels (94%). Lymph node metastases, ER negativity and high histologic grade were also significantly (p < 0.05) associated with poor prognosis. Multivariate analysis revealed that BRCA2 mRNA levels were a significant prognostic factor, being independent of the other conventional prognostic factors. Our results suggest that BRCA2 mRNA levels might serve as a clinically useful prognostic factor in breast cancer patients.     

High expression of MACC1 predicts poor prognosis in patients with osteosarcoma

Increasing evidence has demonstrated that high metastasis-associated in colon cancer-1 (MACC1) level is tightly associated with the development, progression, and poor prognosis of a variety of tumors. However, the relationship between MACC1 and the occurrence, development, and progression of osteosarcoma (OS) remains to be clarified. To facilitate and deepen the understanding of the associations of MACC1 with the development and progression of OS, in the current study, we detected the expressions of MACC1 mRNA and protein, and investigated the relationship between MACC1 expression and prognosis of the patients with OS. Our findings demonstrated that expressions of MACC1 mRNA and protein in OS tissues were significantly higher than those in paired normal bone tissues (P?<?0.05). Additionally, the level of MACC1 mRNA in the patients with higher clinical stage and distant metastasis was markedly higher than those with lower clinical stage and without metastasis (P?<?0.05). Furthermore, high MACC1 level was closely correlated with clinical stage and distant metastasis (P?<?0.05), but not related to the patients’ age, gender, tumor size, and anatomical location (P?>?0.05). Stepwise investigation revealed that survival time of the patients with high MACC1 level was obviously lower than that with low MACC1 level (P?<?0.05). Collectively, our data suggest that MACC1 may play important roles in the development and progression of OS, and thus may be considered as a novel molecular target for therapy of the patients with OS.     

High galectin-1 expression correlates with poor prognosis and is involved in epithelial ovarian cancer proliferation and invasion

PurposeGalectin-1 (Gal-1) is a 14-kDa laminin-binding galectin involved in several biological events including regulation of tumour proliferation and metastasis. In this study, we investigated the clinical significance of Gal-1 expression and its functional role in cell proliferation and invasion in epithelial ovarian cancer (EOC).Experimental designWe evaluated the expression of Gal-1 in 52 serous, 11 endometrioid, and 3 mucinous type EOC tumour samples from 66 patients by immunohistochemistry. In vitro experiments were performed to determine the function of Gal-1 in cell survival, proliferation, and invasion in EOC cells using siRNA and anginex, a Gal-1 inhibitor, as well as recombinant Gal-1 protein.ResultsPatients with strong Gal-1 peritumoural staining had poorer progression-free survival (PFS) than patients with weak peritumoural staining (p = 0.03). Inhibition of Gal-1 by siRNA or anginex resulted in the inhibition of cell growth and proliferation of HeyA8 and SKOV3ip1 cells. Moreover, the ability of cells to migrate was significantly reduced by treatment of cells with Gal-1 siRNA but was increased by treatment of cells with recombinant Gal-1. When we evaluated the interaction between fibroblasts (T HESCs) and cancer cells (A2780-CP20), we found that MMP-2 expression in cancer cells was affected by Gal-1 secreted by fibroblast cells, which suggests that Gal-1 in human fibroblasts might affect the invasive abilities of tumour cells.ConclusionOur results suggest that Gal-1 expression is a potential prognostic factor for PFS and that Gal-1 could be a novel treatment target in EOC patients.     

Low expression of cytosolic NOTCH1 predicts poor prognosis of breast cancer patients

The incidence of breast cancer is increasing, and is one of the leading causes of cancer death worldwide. Dysregulation of NOTCH1 signaling is reported in breast cancer. In present study, bioinformatics was utilized to study the expression of NOTCH1 gene in breast cancer from public databases, including the Kaplan-Meier Plotter, PrognoScan, Human Protein Atlas, and cBioPortal. The relationship between NOTCH1 mRNA expression and survival of patients was inconsistent in public databases. In addition, we performed immunohistochemistry (IHC) staining of 135 specimens from our hospital. Lower cytoplasmic staining of NOTCH1 protein was correlated with cancer recurrence, bone metastasis, and a worse disease-free survival of patients, especially those with estrogen receptor-positive and human epidermal growth factor receptor 2-positive (HER2⁺) cancers. In TCGA breast cancer dataset, lower expression of NOTCH1 in breast cancer specimens was correlated with higher level of CCND1 (protein: cyclin D1). Decreased expression of NOTCH1 was correlated with lower level of CCNA1 (protein: cyclin A1), CCND2 (protein: cyclin D2), CCNE1 (protein: cyclin E1), CDK6 (protein: CDK6), and CDKN2C (protein: p18). In conclusion, NOTCH1 mRNA expression is not consistently correlated with clinical outcomes of breast cancer patients. Low cytoplasmic expression of NOTCH1 in IHC study is correlated with poor prognosis of breast cancer patients. Cytoplasmic localization of NOTCH1 protein failed to initial oncogenic signaling in present study. Expression of NOTCH1 mRNA was discordant with cell cycle-related genes. Regulation of NOTCH1 in breast cancer involves gene expression, protein localization and downstream signaling.     

A long noncoding RNA AB073614 promotes tumorigenesis and predicts poor prognosis in ovarian cancer

Long noncoding RNA (lncRNA) profiles in ovarian cancer (OC) remain largely unknown. In the present study, we screened {"type":"entrez-nucleotide","attrs":{"text":"AB073614","term_id":"51555790","term_text":"AB073614"}}AB073614 as a new candidate lncRNA which promotes development of OC, in two independent datasets ({"type":"entrez-geo","attrs":{"text":"GSE18521","term_id":"18521"}}GSE18521 and {"type":"entrez-geo","attrs":{"text":"GSE38666","term_id":"38666"}}GSE38666) from the Gene Expression Omnibus (GEO). The level of {"type":"entrez-nucleotide","attrs":{"text":"AB073614","term_id":"51555790","term_text":"AB073614"}}AB073614 was then detected in 75 paired OC tissues and adjacent normal tissues by qRT-PCR. Results showed that {"type":"entrez-nucleotide","attrs":{"text":"AB073614","term_id":"51555790","term_text":"AB073614"}}AB073614 expression was significantly up-regulated in 85.3% (64/75) cancerous tissues compared with normal counterparts (P < 0.01). Further, the 5-year overall survival (OS) in OC patients with high expression of {"type":"entrez-nucleotide","attrs":{"text":"AB073614","term_id":"51555790","term_text":"AB073614"}}AB073614 was inferior to that with low expression (17.2 months vs 30.0 months, P = 0.0025). To investigate the functional role of {"type":"entrez-nucleotide","attrs":{"text":"AB073614","term_id":"51555790","term_text":"AB073614"}}AB073614, {"type":"entrez-nucleotide","attrs":{"text":"AB073614","term_id":"51555790","term_text":"AB073614"}}AB073614 siRNA was transfected into OC cell lines. Knockdown of {"type":"entrez-nucleotide","attrs":{"text":"AB073614","term_id":"51555790","term_text":"AB073614"}}AB073614 expression significantly inhibited cell proliferation and invasion, resulted in cell arrest in G₁ phase of cell cycle and a dramatic increase of apoptosis, both in HO-8910 and OVCAR3 cells. In vivo experiment also revealed that knockdown {"type":"entrez-nucleotide","attrs":{"text":"AB073614","term_id":"51555790","term_text":"AB073614"}}AB073614 inhibited OVCAR3 cells proliferation. Finally, western blot assays indicated that lncRNA {"type":"entrez-nucleotide","attrs":{"text":"AB073614","term_id":"51555790","term_text":"AB073614"}}AB073614 may exert its function by targeting ERK1/2 and AKT-mediated signaling pathway. In conclusion, our study suggests that lncRNA {"type":"entrez-nucleotide","attrs":{"text":"AB073614","term_id":"51555790","term_text":"AB073614"}}AB073614 acts as a functional oncogene in OC development.     

Transketolase-like protein 1 expression predicts poor prognosis in colorectal cancer

Background: Transketolase-like protein 1 (TKTL1) is an isoform of tranketolase, a key protein in a cancer cell's glucose metabolism that causes rapid cell growth and controls the non-oxidative part of the pentose phosphate pathway (PPP). Its overexpression occurs in several human cancer types. Our purpose was to study whether TKTL1 expression in colorectal cancer tissue associates with these patients’ prognosis. Methods: We collected retrospectively patient data and tissue samples from 840 colorectal cancer patients treated at Helsinki University Hospital, then stained tumor tissue microarrays for TKTL1 by immunohistochemistry, and compared immunohistochemical tissue expression with clinico-pathological parameters and survival. Results: High expression of TKTL1 associated with high Dukes stage, non-mucinous adenocarcinoma, and left-sided disease. Patients with high TKTL1 expression had poorer prognosis than those with low expression, with a 5-year disease-specific survival of 55.7% vs. 62.7%. Conclusion: We show that high TKTL1 in tumor tissue can lead to poor survival in colorectal cancer. TKTL1 thus can serve as a candidate marker for identifying patients at risk of recurrent disease.     

Upregulation of LINC00659 expression predicts a poor prognosis and promotes migration and invasion of gastric cancer cells

Long non-coding RNAs (lncRNAs) serve an important role in the progression of cancer. LINC00659 was recently identified as a novel oncogenic lncRNA involved in colon cancer cell proliferation via modulating the cell cycle. However, the function of LINC00659 in other types of cancer, especially in gastric cancer (GC), remains unknown. In the present study, bioinformatics analysis combined with cell experiments were performed to explore the function of LINC00659 in GC. It was revealed that LINC00659 expression was significantly upregulated in GC tissues and cell lines. Increased levels of LINC00659 were associated with advanced tumor stage and unfavorable prognosis of patients with GC. Additionally, upregulated LINC00659 expression promoted the migration and invasion of GC cells. Further analysis using a bioinformatics method revealed that matrix metalloproteinase 15 and IQ motif-containing GTPase activating protein 3 were potential downstream targets of LINC00659 involved in tumor metastasis, although the precise underlying mechanism requires further exploration.     

High expression of Wilms' tumor suppressor gene predicts poor prognosis in breast cancer patients.

PURPOSE: The prognostic significance of the Wilms' tumor suppressor gene(WT1) mRNA expression was evaluated in patients with invasive breast cancer. EXPERIMENTAL DESIGN: WT1 mRNA expression in tumor tissues (n = 99) was examined by a quantitative, real-time PCR assay. RESULTS: No significant association was observed between WT1 mRNA levels and clinicopathological parameters such as menopausal status, tumor size, lymph node status, histological grade, and estrogen receptor status. Five-year disease-free survival rate of patients with high WT1 mRNA levels (62.6%) was significantly (P < 0.05) poorer than those with low WT1 mRNA levels (77.2%). Lymph node metastasis (P < 0.05), high histological grade (P < 0.01), and estrogen receptor negativity (P < 0.05) were also significantly associated with poor prognosis, respectively. Multivariate analysis revealed that WT1 mRNA levels were a significant prognostic factor, independent of the other conventional prognostic factors. CONCLUSIONS: These results suggest that measurement of WT1 mRNA levels in tumor tissues might be useful as a new prognostic factor in breast cancer patients.     

High expression of Lin28 is associated with tumour aggressiveness and poor prognosis of patients in oesophagus cancer

Background:

Lin28 is a negative regulator of the tumour suppressor microRNA, let-7, suggesting its role in tumourigenesis. However, the clinical significance of Lin28 expression in oesophageal cancer has not been elucidated.

Methods:

Lin28 and Lin28B expression was examined by immunohistochemistry in 161 tissues from patients with oesophageal cancer who had undergone curative surgery. The relationship between the expressions of Lin28 and Lin28B and various clinicopathological factors was examined. In vitro assays were conducted to determine the role of Lin28 in aggressiveness of oesophageal cancers using oesophageal cancer cell line.

Results:

Lin28 and Lin28B were overexpressed in oesophageal cancer cells compared with non-cancerous epithelial cells, especially in the invasive front. High expression of Lin28 and Lin28B correlated significantly with lymph node metastasis and poor prognosis. High expression of Lin28B expression correlated significantly with low expression of let-7. Multivariate analysis also identified Lin28B expression as an independent prognostic factor. In vitro assays showed that the proliferative and invasive activities were significantly reduced in Lin28B-knockdown cells, compared with control cells.

Conclusion:

High expression of Lin28 is associated with poor prognosis and high tumour aggressiveness in oesophageal cancer and these effects are mediated through increased proliferation and invasiveness of oesophageal cancer cells.     

High Sam68 expression predicts poor prognosis in non-small cell lung cancer

Background

The nuclear protein Sam68 has been implicated in the oncogenesis and tumor growth. The aim of this study was to explore the clinical value of Sam68 in patients with non-small cell lung cancer (NSCLC).

Methods

We examined Sam68 expression in 50 NSCLC tissues and matched adjacent noncancerous tissues by quantitative RT-PCR (qRT-PCR) and Western blotting. Furthermore, the Sam68 protein expression was analyzed by immunohistochemistry in 208 NSCLC samples. Kaplan–Meier method and multivariate Cox regression model were used to evaluate the prognostic value of nuclear Sam68 expression in NSCLC for disease survival.

Results

The expression of Sam68 was significantly elevated in NSCLC tissues as compared with adjacent non-cancerous tissues (P < 0.01). The high expression of Sam68 in NSCLC was significantly correlated with lymph node metastasis and tumor TNM stage. Kaplan–Meier survival analysis revealed that high expression of Sam68 correlated with poor prognosis of NSCLC patients (P < 0.01). Multivariate analysis showed that Sam68 expression was an independent prognostic marker for overall survival of NSCLC patients (HR 2.73, 95 % CI 1.549–4.315, P = 0.002).

Conclusion

Our results suggest that high Sam68 expression predicts poor prognosis of NSCLC patients, and Sam68 may be potentially a prognostic biomarker for NSCLC.     

Decreased TIP30 expression predicts poor prognosis in pancreatic cancer patients

Pancreatic ductal adenocarcinoma (PDAC) is known for its aggressive growth, and is characterized by early tissue invasion and metastasis with poor prognosis. Identifying prognostic markers and delineating the underlying mechanisms that promote progression of PDAC are important for the treatment of pancreatic cancer. TIP30, a newly identified tumor suppressor, appears to be involved in multiple processes during tumor development and metastasis. Here, we investigated the expression of TIP30 in PDAC and its prognostic value in PDAC patients. We examined the expression of TIP30 by immunohistochemistry in tissue microarrays containing 106 surgically resected PDAC. Kaplan–Meier analysis and Cox proportional hazards regression modeling analysis showed that TIP30 expression independently predicted better survival in pancreatectomy patients (p < 0.01). Moreover, decreased TIP30 expression was associated with lymph node metastasis (p < 0.05) and loss of E‐cadherin expression (r = 0.329, p < 0.01). Suppression of TIP30 resulted in upregulation of Snail and subsequent downregulation of E‐cadherin in SW1990 cells containing high‐level of endogenous TIP30. However, in the PANC‐1 cells containing low level of endogenous TIP30, suppressing TIP30 caused upregulation of Slug instead of Snail, followed by upregulation of MMP9 rather than E‐cadherin. Taken together, our work reveals that decreased TIP30 expression is able to enhance invasion and metastasis of pancreatic cancer cells through upregulation of the Snail family members and may serve as an independent predictor for poor outcomes in PDAC patients.     

High visfatin expression predicts poor prognosis of upper tract urothelial carcinoma patients

Visfatin, a newly discovered adipocytokine, is a pro-inflammatory cytokine. This study aimed to evaluate the predictive value of visfatin on prognosis of patients with upper tract urothelial carcinoma. One-hundred and five patients (median age=64, range=24-84 years) were included in this study. Visfatin expression in upper tract urothelial carcinoma tissues was analyzed by immunohistochemistry. Visfatin expression was correlated with clinicopathologic variables using the χ² test. The prognostic value of visfatin for recurrence-free and cancer-specific survival was evaluated by Kaplan-Meier estimates, and the significance of differences between curves was evaluated by the log-rank test. Cox regression model was also used to evaluate the hazard ratios of visfatin on survival. High visfatin expression in upper tract urothelial carcinoma tissues was significantly correlated with tumor stage (P=0.001), grade (P=0.007) and p53 expression (P=0.07). High visfatin expression was associated with poor recurrence-free and cancer-specific survival. Cox regression analysis also revealed that visfatin is an independent predictor of recurrence-free (HR=3.22, P=0.009) and cancer-specific survival (HR=5.74, P=0.023). Our findings indicated that higher visfatin expression is a potential biomarker to predict patient survival. Further study is necessary to investigate the role of visfatin in the carcinogenesis of upper tract urothelial carcinoma.     

Overexpression of long non-coding RNA TUG1 predicts poor prognosis and promotes cancer cell proliferation and migration in high-grade muscle-invasive bladder cancer

Long non-coding RNA TUG1 is involved in the development and progression of a variety of tumors. Little is known about TUG1 function in high-grade muscle-invasive bladder cancer (MIBC). The aims of our study were to determine expression levels of long non-coding RNA TUG1 in tumor tissue, to evaluate its relationship with clinico-pathological features of high-grade MIBC, and to describe its function in MIBC cells in vitro. TUG1 expression levels were determined in paired tumor and adjacent non-tumor bladder tissues of 47 patients with high-grade MIBC using real-time PCR. Cell line T-24 and siRNA silencing were used to study the TUG1 function in vitro. We observed significantly increased levels of TUG1 in tumor tissue in comparison to adjacent non-tumor bladder tissue (P < 0.0001). TUG1 levels were significantly increased in metastatic tumors (P = 0.0147) and were associated with shorter overall survival of MIBC patients (P = 0.0241). TUG1 silencing in vitro led to 34 % decrease in cancer cell proliferation (P = 0.0004) and 23 % reduction in migration capacity of cancer cells (P < 0.0001). We did not observe any significant effects of TUG1 silencing on cell cycle distribution and number of apoptotic cells. Our study confirmed overexpression of TUG1 in MIBC tumor tissue and described its association with worse overall survival in high-grade MIBC patients. Together with in vitro observations, these data suggest an oncogenic role of TUG1 and its potential usage as biomarker or therapeutic target in MIBC.