Increased levels of LAPTM4B, VEGF and survivin are correlated with tumor progression and poor prognosis in breast cancer patients.
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ABSTRACT:
SUBMITTER: Li S
PROVIDER: S-EPMC5522199 | biostudies-other | 2017 Jun
REPOSITORIES: biostudies-other
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Project description:Despite its rare incidence worldwide, penile squamous cell carcinoma (PeSCC) still presents with significant morbidity and mortality due to the limited treatment options for advanced patients, especially those in developing countries. The program death-1 (PD-1)/PD-1 ligand (PD-L1) axis has been demonstrated to play an important role in tumor immune escape, and immunotherapies targeting this pathway have shown great success in certain cancer types. Here, we analyzed the expression pattern of PD-L1 in tumor cells and tumor-infiltrating lymphocytes (TILs) in PeSCC with a multi-center cohort. We found that the majority of PeSCCs (53.4%) were PD-L1-positive and that high PD-L1 expression in tumor cells was associated with a poor prognosis. Notably, PD-L1 expression in tumor cells was significantly associated with the extent of TILs and CD8+ TILs. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) showed that PD-L1 was positively correlated with interferon-gamma (IFNγ) and CD8+ gene expression. Moreover, we defined the constitutive and inducible surface expression of PD-L1 in newly established primary PeSCC cell lines. Interestingly, two PeSCC cell lines had high intrinsic PD-L1 expression. Another cell line showed low PD-L1 expression, but the PD-L1 expression could be induced by IFNγ stimulation. Overall, our data showed that high PD-L1 expression in penile tumor cells indicated a poor prognosis. The upregulation of PD-L1 in PeSCC included both extrinsic and intrinsic mechanisms. These findings indicated that the PD-1/PD-L1 axis might be a potential therapeutic target for patients with penile squamous cell carcinoma.
| S-EPMC5353932 | biostudies-literature
Project description:Esophageal squamous cell carcinoma (ESCC) is a deadly malignant tumor that threatens human health. Long noncoding RNA (lncRNA) is widely expressed in eukaryotes and is closely associated with human disease progression. However, its role in ESCC remains incompletely understood. In this study, we analyzed the results of three gene expression omnibus (GEO) databases containing lncRNA expression data of ESCC and normal tissues. The results showed that HCP5 was significantly overexpressed in ESCC tissues, which was further verified in our collected ESCC samples. The functional study suggested that HCP5 knockdown inhibited ESCC cell proliferation and invasion. Regarding the mechanism, HCP5 was able to directly interact with YTHDF1, a N6-methyladenosine (m6A) reader, enhancing the binding of YTHDF1 to m6A-modified HK2 mRNA, leading to increasing HK2 stability, thereby promoting the Warburg effect (aerobic glycolysis) of ESCC cells. The nude mice model showed that the knockdown of HCP5 in vivo remarkably reduced tumor size. Clinically, high HCP5 was positively correlated with larger tumor volume, higher TNM stage and lymph node metastasis. Moreover, ESCC patients with high HCP5 exerted shorter survival time than patients with low HCP5. These findings uncover the importance of HCP5 in human ESCC progression; the turbulence of HCP5/YTHDF1/HK2 axis may be responsible for ESCC carcinogenicity.
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Project description:BackgroundProstate tumor overexpressed 1 (PTOV1) was demonstrated to play an important role in cancer progression and was correlated with unfavorable clinical outcome. However, the clinical role of PTOV1 in cancer remains largely unknown. This study aimed to investigate the expression and clinicopathological significance of PTOV1 in breast cancer.MethodsThe mRNA and protein expression levels of PTOV1 were analyzed in 12 breast cancer cell lines and eight paired breast cancer tumors by semi-quantitative real time-PCR and western blotting, respectively. Immunohistochemistry was performed to assess PTOV1 protein expression in 169 paraffin-embedded, archived breast cancer samples. Survival analysis and Cox regression analysis were performed to investigate the clinicopathological significance of PTOV1 expression.ResultsOur data revealed that PTOV1 was frequently overexpressed in breast cancer cell lines compared to normal human breast epithelial cells and in primary breast cancer samples compared to adjacent noncancerous breast tissues, at both the mRNA and protein levels. Moreover, high expression of PTOV1 in breast cancer is strongly associated with clinicopathological characteristics and estrogen receptor expression status (P = 0.003). Breast cancer patients with higher PTOV1 expression had substantially shorter survival times than patients with lower PTOV1 expression (P < 0.001). Univariate and multivariate analysis revealed that PTOV1 might be an independent prognostic factor for breast cancer patients (P = 0.005).ConclusionsOur study showed that PTOV1 is upregulated in breast cancer cell lines and clinical samples, and its expression was positively associated with progression and aggressiveness of breast cancer, suggesting that PTOV1 could serve as an independent prognostic marker.
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Project description:The prognosis for pancreatic ductal adenocarcinoma (PDAC) patients is still dismal. Elucidation of associated genomic alteration may provide effective therapeutic strategies for PDAC treatment. NIMA-related protein kinase 7 is widely expressed in various tumors, including breast cancer, colorectal cancer and lung cancer, and promotes the proliferation of liver cancer cells in vitro and in vivo. We investigated the protein expression level of NEK7 in tumor tissues and adjacent normal tissues using immunohistochemistry of 90 patients with PADC. Meanwhile, the RNA expression level of NEK7 was examined using database-based bioinformatic analysis. Correlation and significance of NEK7 expression with patient clinicopathological features and prognosis were examined. Cell proliferation, cell adhesion, migration and invasion capabilities were measured following downregulation of NEK7 expression. 3D tumor organoids of pancreatic cancer were established and splenic xenografted into nude mice, then liver metastatic ability of NEK7 was evaluated in following 4 weeks. We observed NEK7 expression was upregulated in tumor tissues compared to normal tissues at both RNA and protein levels using bioinformatic analysis and immunohistochemistry analysis in PDAC. NEK7 expression was undetectable in normal pancreatic ducts; NEK7 was overexpressed in primary tumor of PDAC; NEK7 expression was highly correlated with advanced T stage, poorly differentiated histological grade invasive ductal carcinoma, and lymphatic invasion. Meanwhile, patients with higher NEK7 expression accompanied by worse survival outcome. Moreover, NEK7 promoted migration, invasion, adhesion, proliferation and liver metastatic ability of pancreatic cancer cells. Taken together, our data indicate that NEK7 promotes pancreatic cancer progression and it may be a potential marker for PDAC prognosis.
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Project description:PurposeColorectal cancer (CRC) is the third most common cancer in males and the second in females worldwide with very poor prognosis. Extracellular matrix proteins like collagens play important roles in cancer progression. Collagen type V α2 (COL5A2) is increased in several cancers but its role in cancer remains unclear.MethodsCOL5A2 expression was evaluated by interrogation of public Oncomine gene microarray datasets and immunohistochemistry (IHC) analyses of two tissue microarrays containing 180 paired CRC cases. Survival analysis was performed using Kaplan-Meier survival curve and Cox proportional hazards regression methods. COL5A2 was ectopically expressed in CRC cells, and the cell proliferation was measured using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) method.ResultsCOL5A2 gene was significantly upregulated in the most types of CRC comparing with the normal counterparts. The mRNA expression of COL5A2 was associated with cancer stages, gender, recurrence, microsatellite instability and KRAS status of CRC. COL5A2 protein increased in the cancer epithelial cells comparing with the normal counterpart and associated with age and T stage of CRC, whereas stromal expression of COL5A2 has no significant change between cancerous and normal tissues. COL5A2 gene and protein (epithelial expression) are independent risk factors and predict poor prognosis of CRC. Ectopic expression of COL5A2 drives colon cancer cell growth and upregulates WNT/β-catenin and PI3K/mTOR signaling via binding DDR1.ConclusionCOL5A2 is a potential prognostic marker of CRC.
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Project description:BackgroundPrevious reports show that phospholipase C epsilon-1 (PLCE1) expression is positively correlated with esophageal squamous cell carcinoma and gastric cardia adenocarcinomas; however, the expression of PLCE1 in hepatocellular carcinoma (HCC) and its correlation with clinical outcome still remain unclear. The aim of this study was to explore the expression of PLCE1 in HCC tissue and to determine whether PLCE1 was a prognostic factor for HCC patients.Materials and methodsPLCE1 levels in 20 paired HCC tissues and corresponding paracarcinomatous tissues was investigated by quantitative real-time polymerase chain reaction and Western blot assays. In addition, protein levels of PLCE1 in one normal liver epithelial cell and four HCC cell lines were examined using Western blot assay. Moreover, immunohistochemistry was applied to determine the expression of PLCE1 in HCC and corresponding surrounding tissues from 90 patients. Statistical analyses were used to examine the association between PLCE1 levels and clinicopathological features.ResultsWe found that the expression of PLCE1 in tumor tissues was significantly lower than those in paracarcinomatous tissues at both mRNA and protein levels (P<0.05). We also determined that PLCE1 protein expression levels were lower in HCC cell lines than normal liver epithelial cells (P<0.05). Notably, immunohistochemical assay showed that PLCE1 expression was significantly low in HCC tissues compared with the adjacent normal liver tissues (40% vs 18.9%; P<0.05). Besides, PLCE1 levels were negatively correlated with tumor capsulae, vascular invasion, Edmondson grade, alpha-fetoprotein, and tumor-node-metastasis stage (P<0.05). Univariate analysis revealed that lower level expression of PLCE1 was significantly associated with poorer overall survival (OS) rate (P<0.001) and disease-free survival rate (P<0.001). Multivariate analysis revealed that low PLCE1 level was an independent poor prognostic factor of OS and recurrence-free survival (P<0.001 and P=0.003, respectively).ConclusionIn brief, our results revealed that decreased PLCE1 expression was associated with tumor progression in HCC and may function as a promising biomarker for HCC prognosis.
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Project description:Neurotrophic factors have been investigated in relation to depression. The aim of the present study was to widen this focus to sortilin, a receptor involved in neurotrophic signalling. The serum sortilin level was investigated in 152 individuals with depression and 216 control individuals, and eight genetic markers located within the SORT1 gene were successfully analysed for association with depression. Genotyping was performed using the Sequenom MassARRAY platform. All the individuals returned a questionnaire and participated in a semi-structured diagnostic interview. Sortilin levels were measured by immunoassay, and potential determinants of the serum sortilin level were assessed by generalized linear models. Serum levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were measured in previous studies. We identified a significant increase of serum sortilin levels in depressed individuals compared with controls (P=0.0002) and significant positive correlation between serum sortilin levels and the corresponding levels of BDNF and VEGF. None of the genotyped SNPs were associated with depression. Additional analyses showed that the serum sortilin level was influenced by several other factors. Alcohol intake and body mass index, as well as depression, serum BDNF and serum VEGF were identified as predictors of serum sortilin levels in our final multivariate model. In conclusion, the results suggest a role of circulating sortilin in depression which may relate to altered activity of neurotrophic factors.
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Project description:YAP-TEAD complex plays an important role in tumorigenesis. 5-HT is proved to upregulate YAP expression by our previous study and VGLL4 is found to compete with YAP for binding to TEAD in several of cancers. Here, we investigated whether 5-HT could affect progression and prognosis of hepatocellular carcinoma (HCC) patients and regulate YAP/VGLL4 balance. We found that 5-HT and YAP/VGLL4 ratio were higher in HCC patients and closely related with progression and poor prognosis. Furthermore, 5-HT level, YAP/VGLL4 ratio and tumor size were proved as independent risk factors of HCC patients in our study. Based on the independent risk factors, nomogram was established to exactly predict prognosis of HCC patients. Additionally, the study revealed that a higher total point of the nomogram was closely correlated with poorer prognosis. As a result, 5-HT might contribute to the progression and poor prognosis of hepatocellular carcinoma via regulating YAP/VGLL4 balance. Therefore, the established nomogram based on the independent risk factors may become an important part of HCC prediction system and YAP/VGLL4 balance may be a potential therapeutic target in future.
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