Exo70 is an independent prognostic factor in colon cancer.
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ABSTRACT:
SUBMITTER: Xiao L
PROVIDER: S-EPMC5505949 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ProposeWe aimed to explore the potential molecular mechanism and independent prognostic genes for colon cancer (CC).MethodsMicroarray datasets GSE17536 and GSE39582 were downloaded from Gene Expression Omnibus. Meanwhile, the whole CC-related dataset were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNA (DEMs) were identified between cancer tissue samples and para-carcinoma tissue samples in TCGA dataset, followed by the KEGG pathway and GO function analyses. Furthermore, the clinical prognostic analysis including overall survival (OS) and disease-free survival (DFS) were performed in all three datasets.ResultsA total of 633 up- and 321 down-regulated mRNAs were revealed in TCGA dataset. The up-regulated mRNAs were mainly assembled in functions including extracellular matrix and pathways including Wnt signaling. The down-regulated mRNAs were mainly assembled in functions like Digestion and pathways like Drug metabolism. Furthermore, up-regulation of UL16-binding protein 2 (ULBP2) was associated with OS in CC patients. A total of 12 DEMs including Surfactant Associated 2 (SFTA2) were potential DFS prognostic genes in CC patients. Meanwhile, the GRP and Transmembrane Protein 37 (TMEM37) were two outstanding independent DFS prognostic genes in CC.ConclusionsULBP2 might be a potential novel OS prognostic biomarker in CC, while GRP and TMEM37 could be served as the independent DFS prognostic genes in CC. Furthermore, functions including extracellular matrix and digestion, as well as pathways including Wnt signaling and drug metabolism might play important roles in the process of CC.
| S-EPMC5897983 | biostudies-literature
Project description:Integrin ?4 (ITGB4) has been reported to be involved in carcinomas. Currently, ITGB4 has been characterized in colon cancer, however, its clinical significance is not very clear. In the present study, we utilized the large public datasets from NCBI Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and collected clinical samples in our center to investigate the transcriptional expressions of ITGB4 in colon cancer, and then explored the associations of ITGB4 with clinicopathological features and overall survival. The statistical analyses suggested that ITGB4 mRNA expressions were up-regulated significantly in colon cancer. High ITGB4 expression was observed to be associated with elder onset age, proximal tumor location, and high microsatellite instability (MSH) status. Further, Kaplan-Meier curves and univariate analysis demonstrated high ITGB4 expression was significantly associated with unfavorable overall survival in colon cancer (HR=1.292, 95%CI=1.084-1.540, P=0.004). And significant association was also found after adjusting the confounding factors including age, gender, and stage (adjusted HR=1.254, 95%CI=1.050-1.497, P=0.012). The annotation of ITGB4 co-expressed genes suggested the pathways including cell growth, positive regulation of cell migration, and apoptotic signaling might be involved in the potential mechanisms of ITGB4 in colon cancer development. The molecular regulation mechanism of ITGB4 ectopic expression in colon cancer was also explored and the results indicated that ITGB4 might be up-regulated by the transcription factor FOSL1 (FOS like 1, AP-1 Transcription Factor Subunit) and its promoter hypomethylation. Our results revealed that ITGB4 might be a therapeutic target and prognosis marker for individual therapy of colon cancer.
| S-EPMC6775604 | biostudies-literature
Project description:Diabetes mellitus (DM) has been associated with an increased risk of colorectal cancer (CRC). The American College of Gastroenterology Guidelines for Colorectal Cancer Screening 2008 recommend that clinicians be aware of an increased CRC risk in patients with smoking and obesity, but do not highlight the increase in CRC risk in patients with DM. To provide an updated quantitative assessment of the association of DM with colon cancer (CC) and rectal cancer (RC), we conducted a meta-analysis of case-control and cohort studies. We also evaluated whether the association varied by sex, and assessed potential confounders including obesity, smoking, and exercise.We identified studies by searching the EMBASE and MEDLINE databases (from inception through 31 December 2009) and by searching bibliographies of relevant articles. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with fixed- and random-effects models. Several subgroup analyses were performed to explore potential study heterogeneity and bias.DM was associated with an increased risk of CC (summary RR 1.38, 95% CI 1.26-1.51; n=14 studies) and RC (summary RR 1.20, 95% CI 1.09-1.31; n=12 studies). The association remained when we limited the meta-analysis to studies that either controlled for smoking and obesity, or for smoking, obesity, and physical exercise. DM was associated with an increased risk of CC for both men (summary RR 1.43, 95% CI 1.30-1.57; n=11 studies) and women (summary RR 1.35, 95% CI 1.14-1.53; n=10 studies). For RC, there was a significant association between DM and cancer risk for men (summary RR 1.22, 95% CI 1.07-1.40; n=8 studies), but not for women (summary RR 1.09, 95% CI=0.99-1.19; n=8 studies).These data suggest that DM is an independent risk factor for colon and rectal cancer. Although these findings are based on observational epidemiological studies that have inherent limitations due to diagnostic bias and confounding, subgroup analyses confirmed the consistency of our findings across study type and population. This information can inform risk models and specialty society CRC screening guidelines.
| S-EPMC3741453 | biostudies-literature
Project description:Glutaredoxin 2 (Grx2; Glrx2) is a glutathione-dependent oxidoreductase located in mitochondria, which is central to the regulation of glutathione homeostasis and mitochondrial redox, and plays a crucial role in highly metabolic tissues. In response to mitochondrial redox signals and oxidative stress, Grx2 can catalyze the oxidation and S-glutathionylation of membrane-bound thiol proteins in mitochondria. Therefore, it can have a significant impact on cancer development. To investigate this further, we performed an immunohistochemical analysis of Grx2 protein expression in colon adenocarcinoma samples collected from patients with primary colon adenocarcinoma (stage I and II) and patients with metastasis to regional lymph nodes (stage III). The results of our study revealed a significant relationship between the immunohistochemical expression of Grx2 and tumor histological grade, depth of invasion, regional lymph node involvement, angioinvasion, staging, and PCNA immunohistochemical expression. It was found that 87% of patients with stage I had high levels of Grx2 expression. In contrast, only 33% of patients with stage II and 1% of patients with stage III had high levels of Grx2 expression. Moreover, the multivariate analysis revealed that the immunohistochemical expression of Grx2 protein apart from the grade of tumor differentiation was an independent prognostic factors for the survival of patients with colon adenocarcinoma. Studies analyzing Grx2 levels in patients' blood confirmed that the highest levels of serum Grx2 protein was also found in stage I patients, which was reflected in the survival curves. A higher level of Grx2 in the serum has been associated with a more favorable outcome. These results were supported by in vitro analysis conducted on colorectal cancer cell lines that corresponded to stages I, II, and III of colorectal cancer, using qRT-PCR and Western Blot.
| S-EPMC10816802 | biostudies-literature
Project description:BackgroundColon cancer is a common malignant tumor with a poor prognosis. Abnormal alternative splicing (AS) events played a part in the occurrence and metastasis of the tumor. We aimed to develop a survival-associated AS signature in colon cancer.MethodsThe Percent Spliced In values of AS events were available in The Cancer Genome Atlas (TCGA) SpliceSeq database. Univariate Cox analysis was carried out to detect the prognosis-related AS events. We created a predictive model on account of the survival-associated AS events, which was further validated with a training-testing group design. Kaplan-Meier analysis was applied to assess patient survival. The area under curve (AUC) of receiver operating characteristic (ROC) was performed to evaluate the predictive values of this model. Meanwhile, the clinical relevance of the signature and its regulatory relationship with splicing factors (SFs) were also evaluated.ResultsIn total, 2132 survival-related AS events were identified from colon cancer samples. We developed an eleven-AS signature, in which the 5-year AUC value was 0.911. Meanwhile, the AUC values at five years were 0.782 and 0.855 in the testing and entire cohort, respectively. Multivariate Cox regression displayed that the T category and the risk score of the signature were independent risk factors of colon cancer survival. Also, we constructed an SFs-AS network based on 11 SFs and 48 AS events.ConclusionsWe identified an eleven-AS signature of colon cancer. This signature could be treated as an independent prognostic factor.
| S-EPMC7510085 | biostudies-literature
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.
| S-EPMC8130162 | biostudies-literature
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.
| S-EPMC7763268 | biostudies-literature
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.
| S-EPMC6607603 | biostudies-literature
Project description:INTRODUCTION:Prognostic nutritional index (PNI) reflects the nutritional and immunologic status of the patients. The clinical application of PNI is already well-known in various kinds of solid tumors. However, there is no study investigating the relationship between PNI and oncological outcome of the resected ampulla of Vater (AoV) cancer. MATERIALS AND METHODS:From January 2005 to December 2012, the medical records of patients who underwent pancreaticoduodenectomy for pathologically confirmed AoV cancer were retrospectively reviewed. Long-term oncological outcomes were compared according to the preoperative PNI value. RESULT:A total of 118 patients were enrolled in this study. The preoperative PNI was 46.13±6.63, while the mean disease-free survival was 43.88 months and the mean disease-specific survival was 55.3 months. In the multivariate Cox analysis, initial CA19-9 (p = 0.0399), lymphovascular invasion (p = 0.0031), AJCC 8th N-stage (p = 0.0018), and preoperative PNI (p = 0.0081) were identified as significant prognostic factors for resected AoV cancer. The disease-specific survival was better in the high preoperative PNI group (?48.85: 40.77 months vs. >48.85: 68.05 months, p = 0.0015). A highly accurate nomogram was developed based on four clinical components to predict the 1, 3, and 5-year disease-specific survival probability (C-index 0.8169, 0.8426, and 0.8233, respectively). CONCLUSION:In resected AoV cancer, preoperative PNI can play a significant role as an independent prognostic factor for predicting disease-specific survival.
| S-EPMC7053754 | biostudies-literature
Project description:To clarify the function of cyclin A2 in colon homeostasis and colorectal cancer (CRC), we generated mice deficient for cyclin A2 in colonic epithelial cells (CECs). Colons of these mice displayed architectural changes in the mucosa and signs of inflammation, as well as increased proliferation of CECs associated with the appearance of low- and high-grade dysplasias. The main initial events triggering those alterations in cyclin A2-deficient CECs appeared to be abnormal mitoses and DNA damage. Cyclin A2 deletion in CECs promoted the development of dysplasia and adenocarcinomas in a murine colitis-associated cancer model. We next explored the status of cyclin A2 expression in clinical CRC samples at the mRNA and protein levels and found higher expression in tumors of patients with stage 1 or 2 CRC compared with those of patients with stage 3 or 4 CRC. A meta-analysis of 11 transcriptome data sets comprising 2239 primary CRC tumors revealed different expression levels of CCNA2 (the mRNA coding for cyclin A2) among the CRC tumor subtypes, with the highest expression detected in consensus molecular subtype 1 (CMS1) and the lowest in CMS4 tumors. Moreover, we found high expression of CCNA2 to be a new, independent prognosis factor for CRC tumors.
| S-EPMC7880422 | biostudies-literature