Abnormal Fhit expression is an independent poor prognostic factor for cervical cancer.
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ABSTRACT:
SUBMITTER: Takizawa S
PROVIDER: S-EPMC2747578 | biostudies-other | 2003 Apr
REPOSITORIES: biostudies-other
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Project description:Abnormal fragile histidine triad transcripts were found in 20-30% of CIN2/3 lesions and 11% of normal cervical biopsies by RT-PCR. Bi-allelic loss of the fragile histidine triad gene and the loss of fragile histidine triad protein expression detectable by immunochemical staining with a polyclonal fragile histidine triad specific antibody was rare. The genomic changes showed no association with the presence of human papillomavirus types which carry high risk for cervical cancer (high risk human papillomavirus) as assessed by a type-specific multiplex PCR. The presence of abnormal fragile histidine triad transcripts in a subset of CIN2/3 lesions with no high risk human papillomavirus suggests that this could be an independent risk factor associated with an alternative carcinogenic pathway.
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Project description:ATP binding cassette subfamily D member 3 (ABCD3) is a member of the superfamily of ATP-binding cassette (ABC) transporters, which serve crucial roles in the process of tumor cell resistance to chemotherapy. The present study investigated the diagnostic and prognostic capabilities of ABCD3 in colorectal cancer (CRC) by bioinformatics analysis. Gene expression data and corresponding clinical information of patients with CRC were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The results demonstrated that ABCD3 mRNA level was decreased in CRC tissues compared with normal tissues following Wilcoxon test analysis. Furthermore, ABCD3 protein expression was significantly higher in normal colon tissues compared with colon adenocarcinoma tissues according to the Human Protein Atlas. In addition, the area under the Receiver Operating Characteristic curve based on comparison between the tumor and normal groups derived from TCGA and GEO databases demonstrated that the use of ABCD3 mRNA level may be used for the diagnosis of CRC. ABCD3 expression was significantly associated with clinical stage, T stage, and lymph node status following Kruskal-Wallis test or Wilcoxon rank sum test, logistic regression and χ2 test. Furthermore, the results from Kaplan-Meier survival analysis indicated that low ABCD3 mRNA expression had a poorer prognosis value compared with ABCD3 high expression in patients with CRC. In addition, results from univariate Cox regression analysis indicated that ABCD3 mRNA expression was associated with overall survival (OS), and results from multivariate Cox analysis indicated that ABCD3 mRNA expression may be considered an independent prognostic factor from other clinical factors, such as clinical stage, sex and age. The results from Gene Set Enrichment Analysis demonstrated that the ABCD3 high-expression phenotype was differentially enriched in five biological processes, including apoptosis, cell cycle, renal cell carcinoma, thyroid cancer and colorectal cancer. The findings from this study demonstrated that ABCD3 mRNA expression may be considered as a potential diagnostic and prognostic biomarker in patients with CRC. ABCD3 expression levels may participate in the regulation of cell apoptosis and cell cycle. In addition, GSEA analysis identified Kyoto Encyclopaedia of Genes and Genomes pathways for renal cell carcinoma, thyroid cancer and CRC involving ABCD3.
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Project description:BackgroundAccumulating evidences indicate that the signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) plays a key role in the development and progression of many human cancers. However, the underlying mechanism and prognosis value of SCUBE3 in breast cancer are still unclear.MethodsThe clinical data of 137 patients with breast cancer who underwent surgical resection in Taizhou Hospital of Zhejiang Province were retrospectively analyzed. We first conducted a comprehensive study on the expression pattern of SCUBE3 using the Tumor Immune Estimation Resource (TIMER) and UALCAN databases. In addition, the expression of SCUBE3 in breast tumor tissues was confirmed by immunohistochemistry. The protein-protein interaction analysis and functional enrichment analysis of SCUBE3 were analyzed using the STRING and Enrichr databases. Moreover, tissue microarray (TMA) was used to analyze the relationship between SCUBE3 expression levels and clinical-pathological parameters, such as histological type, grade, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). We further supplemented and identified the above results using the UALCAN and bc-GenExMiner v4.4 databases from TCGA data. The correlation between the expression of SCUBE3 and survival was calculated by multivariate Cox regression analysis to investigate whether SCUBE3 expression may be an independent prognostic factor of breast cancer.ResultsWe found that the expression level of SCUBE3 was significantly upregulated in breast cancer tissue compared with adjacent normal tissues. The results showed that the distribution of breast cancer patients in the high expression group and the low expression group was significantly different in ER, PR, HER2, E-cadherin, and survival state (p < 0.05), but there was no significant difference in histologic grade, histologic type, tumor size, lymph node metastasis, TMN stage, subtypes, or recurrence (p > 0.05). In addition, the high expression of SCUBE3 was associated with relatively poor prognosis of ER- (p = 0.012), PR- (p = 0.029), HER2 + (p = 0.007). The multivariate Cox regression analysis showed that the hazard ratio (HR) was 2.80 (95% CI 1.20-6.51, p = 0.0168) in individuals with high SCUBE3 expression, and HR was increased by 1.86 (95% CI 1.06-3.25, p = 0.0300) for per 1-point increase of SCUBE3 expression.ConclusionsThese findings demonstrate that the high expression of SCUBE3 indicates poor prognosis in breast cancer. SCUBE3 expression may serve as a potential diagnostic indicator of breast cancer.
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Project description:Background: Cadherin EGF LAG Seven-Pass G-Type Receptor 3 (CELSR3) gene was reported to be overexpressed in various human cancers and involved in the regulation of neurite-dependent neurite outgrowth and may play a role in tumor formation. However, the clinical significance of CELSR3 in prostate cancer (PCa) has not been fully studied. Methods: The expression of CELSR3 was detected by crossover analysis of the public datasets and cell lines. MTT assay and migration assay were performed to evaluate the cells' physiological functioning. Co-expressed genes and enrichment analysis was performed to investigate the biological significance of CELSR3 in PCa. Quantitative real-time polymerase chain reaction was used to detect the expression levels of hub genes (CENPE, CENPA, CDC20, NUF2, ESPL1, PLK1) related to CELSR3. Results: We found a significant increase in CELSR3 expression in PCa patients and cell lines. Furthermore, immunohistochemical analysis showed that CELSR3 protein expression was significantly more highly expressed in the PCa tissues compared to the non-cancerous PCa tissues. CELSR3 downregulation significantly suppressed cell proliferation and migration potential. CELSR3-related hub genes (CENPE, CENPA, CDC20, NUF2, ESPL1, PLK1) were selected and the functions of these hub genes showed that the function of CELSR3 was closely related to the cell cycle-related signaling pathways. The upregulation of CELSR3 mRNA expression in the PCa tissues significantly correlated with the presence of high serum PSA levels, high pathological stage, high Gleason score, short overall survival time and short disease-free survival time. Conclusion: Our data suggest that CELSR3 may play an important role in the progression of PCa. More importantly, an increase in CELSR3 expression may be indicative of poor disease-free survival and poor prognosis in PCa patients.
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Project description:NDRG1 is widely described as a metastasis suppressor in breast cancer. However, we found that NDRG1 is critical in promoting tumorigenesis and brain metastasis in mouse models of inflammatory breast cancer (IBC), a rare but highly aggressive form of breast cancer. We hypothesized that NDRG1 is a prognostic marker associated with poor outcome in patients with IBC. NDRG1 levels in tissue microarrays from 64 IBC patients were evaluated by immunohistochemical staining with NDRG1 (32 NDRG1-low (≤median), 32 NDRG1-high (>median)). Overall and disease-free survival (OS and DSS) were analyzed with Kaplan-Meier curves and log-rank test. Univariate analysis showed NDRG1 expression, tumor grade, disease stage, estrogen receptor (ER) status, and receipt of adjuvant radiation to be associated with OS and DSS. NDRG1-high patients had poorer 10-year OS and DSS than NDRG1-low patients (OS, 19% vs. 45%, p = 0.0278; DSS, 22% vs. 52%, p = 0.0139). On multivariable analysis, NDRG1 independently predicted OS (hazard ratio (HR) = 2.034, p = 0.0274) and DSS (HR = 2.287, p = 0.0174). NDRG1-high ER-negative tumors had worse outcomes OS, p = 0.0003; DSS, p = 0.0003; and NDRG1-high tumors that received adjuvant radiation treatment had poor outcomes (OS, p = 0.0088; DSS, p = 0.0093). NDRG1 was a significant independent prognostic factor for OS and DSS in IBC patients. Targeting NDRG1 may represent a novel strategy for improving clinical outcomes for patients with IBC.
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Project description:BACKGROUND:Prognostication of patients with colorectal cancer (CRC) currently relies on tumor-node-metastasis (TNM) staging but clinical outcomes of patients of the same histoclinical stage are heterogeneous. It is therefore imperative to devise novel molecular tests to stratify CRC patients. Our previous work demonstrated that eukaryotic elongation factor-2 kinase (EEF2K) is a tumor suppressor in CRC. Herein, we investigated EEF2K expression in CRC and determined its relationship with clinicopathological parameters. METHODS:Quantitative RT-PCR and Westerns blots were used to examine EEF2K expression in primary tumor and the adjacent non-tumor tissues of CRC patients (n =?20). Kaplan-Meier curves and Cox regression analysis were used to assess the association between clinical outcomes of CRC patients and EEF2K protein expression determined by immunohistochemistry on tissue microarray (n =?151). RESULTS:EEF2K was significantly downregulated at both mRNA and protein levels in tumors of CRC patients. Univariate Cox regression analysis revealed that CRC patients with high tumor grade, advanced TNM staging and low EEF2K expression were associated with worse overall survival. Multivariate analysis further demonstrated that low EEF2K expression was an independent factor for predicting poorer overall survival in CRC patients (p =?0.014; Hazard ratio?=?2.951; 95% confidence interval: 1.240-7.024). The 5-year survival rate was 82.8% in the EEF2K-high-expression group versus 63.9% in the EEF2K-low-expression group (p =?0.0118). The association of overall survival with EEF2K expression in CRC patients was verified in The Cancer Genome Atlas (TCGA) cohort. CONCLUSIONS:EEF2K is downregulated in CRC and its expression can be employed as a prognostic marker for CRC patients independent of TNM staging.
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Project description:PICT1 is a key regulator of the MDM2-TP53 pathway. High mRNA expression levels of PICT1 are associated with poor prognosis in several cancers with wild-type TP53. In this study, we identified the PICT1 protein expression profile in non-small cell lung cancer (NSCLC) with wild-type TP53 in the nucleolus and cytoplasm, and revealed the relationship between PICT1 expression and patient clinicopathological factors. PICT1 expression in the tumor cells of 96 NSCLC patients with wild-type TP53 was evaluated by immunohistochemistry. Forty-three of 96 (44.8%) NSCLC samples were positive for nucleolar PICT1, while 40/96 (41.7%) NSCLC samples were positive for cytoplasmic PICT1. There was no correlation between nucleolar PICT1 expression and clinicopathological factors. However, cytoplasmic PICT1 expression was significantly correlated with sex, smoking history, differentiation, lymphatic invasion and pathological stage. In multivariate analysis, lymphatic invasion was significantly associated with cytoplasmic PICT1 expression (hazard ratio: 5.02, P = 0.026). We scrutinized PICT1 expression in samples of NSCLC with wild-type TP53, and showed a correlation between cytoplasmic PICT1 expression and several clinicopathological factors in these patients. Our results indicate that cytoplasmic PICT1 expression is a poor prognostic factor and is associated with tumor progression via lymphatic invasion in these patients.
| S-EPMC4278310 | biostudies-literature
Project description:BackgroundPelvic lymph node metastasis (LNM) is a crucial independent prognostic factor in cervical cancer (CCa) and serves as an indicator for radiation therapy as the primary or an adjuvant treatment option. However, preoperative diagnosis of LNM remains challenging. Thus, we aimed to identify biomarkers of LNM in patients with presumed early-stage CCa.MethodsThe differentially expressed genes (DEGs) between tumours with different lymph node statuses were identified by using The Cancer Genome Atlas database. Then, univariate Cox regression analysis and Kaplan-Meier analyses were utilized to screen overall survival (OS)-associated genes. Multivariate Cox analysis and logistical analysis were utilized to evaluate independent risk factors for OS and LNM, respectively. Subsequently, the protein level of fatty acid binding protein 4 (FABP4) was detected in normal cervical and CCa tissues by immunohistochemistry assays. EdU assays were performed to determine whether FABP4 altered the proliferation of cervical cancer cells. Wound healing and Transwell assays were conducted to explore the effects of FABP4 depletion on migratory and invasive abilities of cervical cancer cells. F-actin fluorescence staining were performed to investigate morphological change and Western blotting analyses were performed to determine epithelial mesenchymal transition-related marker expression and downstream signalling pathways.ResultsA total of 243 DEGs, including 55 upregulated and 188 downregulated DEGs, were found in CCa patients with LNM versus those without LNM. Among these, FABP4 was found to be closely associated with poor OS. Multivariate analysis uncovered that FABP4 was an independent risk factor for OS and LNM in patients with CCa. The immunohistochemical results verified dramatically increased FABP4 expression in CCa tissues compared to normal cervical epithelia and its association with poor OS and LNM. In vitro, The proliferation, migration and invasion of cervical cancer cells were significantly inhibited after knocking down of FABP4, which was accompanied by elevated expression of E-cadherin and downregulated expression of N-cadherin, Vimentin and p-AKT.ConclusionsFABP4 might be a promising biomarker of LNM and survival in patients with early-stage CCa and therefore could significantly contribute to the development of personalized prognosis prediction and therapy optimization.
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