scholarly journals eIF4E Overexpression Is Associated with Poor Prognoses of Ovarian Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Jun Zheng ◽  
Xueqing Li ◽  
Chunyan Zhang ◽  
Yiqiang Zhang

Aim. Ovarian cancer is a common malignant tumor of the gynecological oncology worldwide, with a high incidence and mortality rate and poor prognosis. Searching for new diagnostic molecular biomarkers for ovarian cancer is extremely significant. Methods. Here, we analyzed the expression rates of eIF4E and cyclin D1 proteins in 123 cases of cancer tissue samples and 38 cases of paracancerous tissue samples and studied the connection between the expression rates of eIF4E and cyclin D1 proteins by immunohistochemistry and statistically correlated with clinicopathological features in ovarian cancer. Results. The results showed that the expression rates of eIF4E and cyclin D1 proteins in ovarian cancer tissues were significantly higher than those in noncancerous epithelial ovarian tissues ( P = 0.001 and P = 0.032 , respectively). Additionally, the results revealed that a higher expression rate of eIF4E ( P = 0.008 ) was found in the advanced stage (stage III/IV), and also patients with cervical lymph node metastasis displayed higher expression of eIF4E ( P < 0.001 ) and cyclin D1 ( P = 0.033 ) than those without lymph node metastasis. Spearman’s rank correlation test showed that there was a significant positive correlation between the eIF4E and cyclin D1 proteins in ovarian cancer. The Kaplan-Meier method showed that patients with lower expression of eIF4E had marginally better survival than those with high expression of eIF4E ( P = 0.012 ). Multivariate Cox regression analysis further identified that positive expression of eIF4E was an independent prognostic factor. Conclusion. In ovarian cancer, eIF4E might be a valuable biomarker to predict poor prognoses and a potential therapeutic target to develop valid treatment strategies.

2021 ◽  
Author(s):  
Shuang Liu ◽  
Zheng Lin ◽  
Jianwen Wang ◽  
Zerong Zheng ◽  
Wenqing Rao ◽  
...  

Abstract Background: To explore the miR-4787-3p expression levels in the serum exosome and tissue and its role in lymph node metastasis and prognosis in ESCC. Methods: The miRNA array was conducted to detect the ESCC serum exosomal miRNAs expression. A receiver operating characteristic (ROC) curve was constructed to determine the predictive ESCC with lymph node metastasis efficacy of serum exosomal miR-4784-3p. The Cox regression analysis was preformed to explore prognostic factors for ESCC. Transwell assay and CCK-8 assays were utilized to evaluate cell migration, invasion, and proliferation, respectively. Results: High serum exosomal miR-4787-3p expression was demonstrated in lymph node metastasis group (P =0.011). The serum exosomal miR-4787-3p expression was significantly associated with histologic grade (P = 0.010), and TNM stage (P = 0.033). However, there was no significant relationship between tissue miR-4787-3p expression and clinical characteristics (P >0.05). ROC analyses revealed that the AUCs of serum exosomal miR-4787-3p for lymph node metastasis prediction was 0.787. The Cox regression analysis found that high expression serum exosomal miR-4787-3p were correlated with poor prognoses (for OS, HR=2.68, 95% CI: 1.02~7.04; for DFS, HR = 2.65, 95% CI: 1.05~6.68). Nevertheless, no association between tissue miR-4787-3p expression and ESCC prognosis. In addition, upregulated expression of miR-4787-3p could promote migration and invasion in vitro. Conclusions: Serum exosomal miR-4787-3p can be promising biomarkers for ESCC metastasis and prognosis


2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Yugang Wu ◽  
Min Jin ◽  
Huanbai Xu ◽  
Zhang Shimin ◽  
Songbing He ◽  
...  

We investigated the clinicopathologic significance of HIF-1, CXCR4, and VEGF expression using immumohistochemistry in human colon cancer. HIF-1, CXCR4, and VEGF high expression levels were correlated positively with TNM stage, lymph node involvement, and distant metastasis Furthermore, we found that combined high expression of any two of the three molecules (P=.028for HIF-1/CXCR4,P=.007for HIF-1/VEGF, andP=.004for CXCR4/VEGF) had stronger correlation with lymph node metastasis than did each alone. However, a relationship with distant metastasis is seen only with the combinations CXCR4/VEGF (P=.069for HIF-1/CXCR4,P=.062for HIF-1/VEGF, andP=.035for CXCR4/VEGF) as compared with those of single molecule high expression alone. Combined expression of all three molecules strongly correlates with lymph node metastasis and distant metastasis. The mRNA expression of HIF-1, CXCR4, and VEGF were quantified by real-time PCR in different colon cancer tissue samples, the experiment results shown that fresh colon tissue samples significantly overexpressed CXCR4 and VEGF mRNA compared with negative control. Therefore, the disease-free survival of all patients after curative resection can be considered in association with all three markers expression.


2021 ◽  
Vol 12 ◽  
Author(s):  
Chao Yang ◽  
Fengyu Cao ◽  
Shuoyang Huang ◽  
Yongbin Zheng

BackgroundAs a heterogeneous disease, colorectal cancer (CRC) presents a great challenge to individualized treatment due to its lymph node metastasis (LNM). Existing studies have shown that immune and stromal components in extracellular matrix (ECM) act as important part in tumorigenicity and progression, while their roles in LNM have not been fully elucidated. Here, crucial ECM-related genes responsible for LNM in CRC were selected by multi-omics analysis.MethodsFirstly, we characterized the immune infiltration landscape of CRC samples from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases by using ssGSEA algorithm. The CRC patients were divided into several immune subgroups by hierarchical clustering analyses. Then, differential genes were identified among immune subgroups and CRC vs. normal tissues in TCGA and GEO GSE39582 cohorts, respectively. Next, weighted correlation network analysis (WGCNA) was employed to construct a co-expression network to find LNM-related modules and hub genes. Subsequently, we evaluated the clinical value of hub gene in prognostic prediction and chemotherapy/immunotherapy. Besides, the protein level of key gene was verified in an external cohort from our center. Finally, we explored the underlying mechanism of FSTL3-mediated LNM by Gene function annotation and correlation analysis.ResultsTwo immune subgroups, namely Immunity_High and Immunity_Low, were defined among the two CRC cohorts using ssGSEA algorithm, respectively. Based on the two immune subgroups, 2,635 overlapping differentially expressed genes were obtained from two cohorts, which were sequentially subjected to WGCNA and univariate Cox regression analysis. Ultimately, FSTL3 was selected as the key gene. Here, we first confirmed that overexpression of FSTL3 correlated with LNM and worse prognosis in CRC and was verified at the protein level in the external validation cohort. Moreover, FSTL3 expression showed strongly positive correlation with immune and stromal components in ECM. We furthermore found that FSTL3 may accelerate LNM through the formation of inhibitory immune microenvironment via promoting macrophage and fibroblast polarization and T cell exhaustion. Interestingly, high FSTL3 expression is linked to chemoresistance, but immunotherapy-sensitive.ConclusionFSTL3 is identified as a biomarker for ECM remodeling and worse clinical outcomes for the first time in CRC and is also a potential immunotherapeutic target to block LNM for CRC.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ming Chen ◽  
Zhenzhen Wen ◽  
Zhengwei Qi ◽  
Min Gao

BackgroundPrimary peritoneal serous carcinoma (PPSC) is a rare tumor that lacks a prognostic prediction model. Our study aims to develop a nomogram to predict overall survival (OS) of PPSC patients.MethodsPatients confirmed to have PPSC between 2004 and 2012 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. LASSO and multivariate Cox regression analyses were used to screen for meaningful independent prognostic factors to construct a nomogram model for 3-, 5-, and 10-year OS among patients with PPSC. The nomogram compared the discrimination, calibration, and net benefits with the International Federation of Gynecology and Obstetrics (FIGO) staging system of PPSC patients.ResultsEight variables were selected to establish the nomogram for PPSC. The established nomogram performed significantly better than the FIGO staging system (p &lt; 0.05). The 3-, 5-, and 10-year OS of PPSC was 0.498, 0.306, and 0.152, respectively. Patients of old age, widowed marital status, grade high, FIGO IIIB, IIIC, or IV, lymph node metastasis, no lymphadenectomy, no surgery, and no chemotherapy got higher score which corresponds with higher risk and lower OS. In the multivariate Cox regression analysis, age, histological grade, FIGO staging, lymph node metastasis, and lymphadenectomy (four or more) were identified as independent prognostic factors for PPSC.ConclusionsPPSC patients have distinct characteristics with respect to their presentation and survival outcomes. A prognostic nomogram constructed by various clinical indicators can provide better and more accurate predictions for patients with PPSC.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17524-e17524
Author(s):  
Jinan Guo ◽  
Wenzhuan Xie ◽  
Mengli Huang ◽  
Chan Gao

e17524 Background: Prostate cancer (PCa) patients with lymph node metastasis (LNM) always exhibit poor clinical outcomes. A gene signature that could predict survival in these patients would allow for earlier detection of mortality risk and will also guide individualized therapy. Methods: A prediction model was developed using a public cohort consisting of 623 patients with clinicopathologically confirmed PCa. Data were gathered from cBioPortal and UCSC Xena. Genes expressed differentially in patients with lymph node metastasis versus those without lymph node metastasis were identified. Uni-variate Cox regression analysis and LASSO Cox regression were applied to build a prediction model. Time-dependent receiver operating characteristic (ROC) and Kaplan-Meier curves were used to assess the prognostic capacity of the model, followed by external validation using the MSKCC dataset from cBioPortal. Gene Set Enrichment Analysis (GSEA) was performed to further understand the underlying molecular mechanisms. Results: We identified a six-gene signature (covering GSDMB, SSTR1, MX1, CCBE1, MYBPC1, and FAM3D) that could effectively identify a high-risk subset of PCa patients. ROC analysis indicated that the signature had a good performance (AUC > 0.7) in survival prediction in both the training and the testing/validation cohorts. Cox regression analysis showed that the six-gene signature could independently predict disease-free survival (DFS) as well, although with lower predictive power. Subgroup analyses showed that signature-based risk score may serve as a promising marker to predict DFS in different subgroups, including stage T2 (HR = 0.12, p < 0.001), stage T3 (HR = 0.29, p < 0.001), TP53-wild-type (HR = 0.22, p < 0.001), TP53-mutated (HR = 0.07, p < 0001), AR pathways-wild-type (HR = 0.2, p < 0.001) and AR pathways-mutated(HR = 0.16, p = 0.0419). The performance of the six-gene signature in LNM+ was stable for stratifying the patients according to risk of deatch (HR = 0.23, p = 0.0333). Moreover, GSEA revealed distinct pathway enrichment features in the different risk groups, where pathways related to DNA repair were more prominently enriched in the high-risk group while the low-risk group had higher enrichment of androgen response. Conclusions: We developed a robust six-gene signature that can effectively classify PCa patients into groups with low- and high-risk group, which may help select high-risk patients who require more aggressive adjuvant target therapy or immune therapy.


2021 ◽  
pp. 1-7
Author(s):  
Lili Huang ◽  
Yan Zhou ◽  
Qiuwei Sun ◽  
Lei Cao ◽  
Xueguang Zhang

BACKGROUND and OBJECTIVE: Gastric adenocarcinoma (GAC) is one of the most common malignancies. Increasing data have indicated a correlation between soluble B7-H3 (sB7-H3) levels and tumor malignancies. In this study, we aim to investigate the level of soluble B7-H3 in serum of GAC patients. Further, we analyze the correlation between sB7-H3 level and tissue B7-H3 expression and explore the clinical evaluation value of sB7-H3 associated with pathological characteristics and prognosis of GAC patients. METHODS: One hundred and twenty-eight serum and tissue samples of GAC 20 serum and tissue samples of gastritis patients and 77 serum, 5 tissue samples of healthy controls were collected. The serum levels of sB7-H3 were detected by Enzyme-linked immunosorbent assay (ELISA), while the expression of membrane B7-H3 (mB7-H3) and Ki67 were evaluated by immunohistochemistry. The correlation between sB7-H3 and mB7-H3, sB7-H3 and Ki67, sB7-H3 or mB7-H3 and clinical features were analyzed by Pearson’s Chi-square test. RESULTS: Both serum level of sB7-H3 and tissue B7-H3 of GAC patients were significantly higher than those of gastritis patients and healthy controls. sB7-H3 level was correlated with total B7-H3 expression in tissues (r= 0.2801, P= 0.0014). Notably, the concentration of sB7-H3 was correlated with its expression of membrane form in tumor cells (r= 0.3251, P= 0.002) while not in stromal cells (r= 0.07676, P= 0.3891). Moreover, the levels of sB7-H3 in patients with TNM stage III/IV or with Infiltration depth T3/T4 or with lymph node metastasis were significantly higher than those of patients with TNM stage I/II (P= 0.0020) or with Infiltration depth T1/T2 (P= 0.0169) or with no lymph node metastasis (P= 0.0086). Tumor B7-H3 score, but not stromal B7-H3 score, in patients with TNM stage III/IV or with lymph node metastasis was significantly higher than those with TNM stage I/II (P= 0.0150) or with no lymph node metastasis (P= 0.182). CONCLUSIONS: Soluble B7-H3 level may reflect the tissue B7-H3 expression on tumor cells of GAC tissues. Elevated level of sB7-H3 in serum suggests poor clinical pathological characteristics of GAC patients.


2021 ◽  
Vol 11 ◽  
Author(s):  
Han Li ◽  
Yucheng Ma ◽  
Zhongyu Jian ◽  
Xi Jin ◽  
Liyuan Xiang ◽  
...  

Background and AimsThe current guidelines for the treatment of penile cancer patients with clinically non-invasive normal inguinal lymph nodes are still broad, so the purpose of this study is to determine which patients are suitable for lymph node dissection (LND).MethodsHistologically confirmed penile cancer patients (primary site labeled as C60.9-Penis) from 2004 to 2016 in the Surveillance, Epidemiology, and Results database were included in this analysis. Univariate and multivariate Cox regression analyses were applied to determine an overall estimate of LND on overall survival and cancer-specific survival. A 1:1 propensity matching analysis (PSM) was applied to enroll balanced baseline cohort, and further Kaplan–Meier (KM) survival analysis was used to get more reliable results.ResultsOut of 4,458 histologically confirmed penile cancer patients with complete follow-up information, 1,052 patients were finally enrolled in this analysis. Age, pathological grade, T stage, and LND were identified as significant predictors for overall survival (OS) in the univariate Cox analysis. In the multivariate Cox regression, age, pathological grade, T stage, and LND were found significant. The same results were also found in the univariate and multivariate Cox regression analyses for cancer-specific survival (CSS). After the successful PSM, further KM analysis revealed that LND could bring significant OS and CSS benefits for T3T4 patients without lymph node metastasis.ConclusionLymph node dissection may bring survival benefits for penile cancer patients without preoperatively detectable lymph node metastasis, especially for T3T4 stage patients. Further randomized control trial is needed.


2021 ◽  
Author(s):  
Thérèse Rachell Theodoro ◽  
Rodrigo Lorenzetti Serrano ◽  
Karine Corcione Turke ◽  
Sarhan Sydney Saad ◽  
Marcelo Augusto Fontenelle Ribeiro Junior ◽  
...  

AbstractThe process of proliferation and invasion of tumor cells depends on changes in the extracellular matrix (ECM) through the activation of enzymes and alterations in the profile of ECM components. We aimed to investigate the mRNA and protein expression of ECM components such as heparanase (HPSE), heparanase-2 (HPSE2), matrix metalloproteinase-9 (MMP-9), and syndecan-1 (SYND1) in neoplastic and non-neoplastic tissues of patients with colorectal carcinoma (CRC). It is a cross-sectional study in which twenty-four adult patients that had CRC were submitted to resection surgery. We analyzed the expression of HPSE, HPSE2, MMP-9, and SYND1 by quantitative RT-PCR and immunohistochemistry. Differing from most of the studies that compare the mRNA expression between tumor samples and non-neoplastic tissues, we decided to investigate whether variations exist in the expression of the ECM components between the affected tissue and nontumoral tissue collected from the same patient with CRC. We removed both tissue samples immediately after the surgical resection of CRC. The data showed higher mRNA and protein expression of HPSE2 (P = 0.0058), MMP-9 (P = 0.0268), and SYND1 (P = 0.0002) in tumor samples compared to the non-neoplastic tissues, while there was only an increase in the level of HPSE protein in tumor tissues. A greater expression of HPSE2 was observed in patients with lymph node metastasis (P = 0.048), suggesting that such protein can be a marker of lymph node metastasis in CRC.


2019 ◽  
Vol 18 ◽  
pp. 153303381989680
Author(s):  
Hongxiao Chen ◽  
Xiufang Tian ◽  
Yajing Luan ◽  
Hui Lu

Emerging evidence have indicated that dysregulated long noncoding ribonucleic acids act as a novel diagnostic and therapeutic target in the progression of ovarian cancer. Long noncoding RNA DiGeorge syndrome critical region gene 5 has been reported to participate in some types of human cancer progresses, but its clinical roles in ovarian cancer had been rarely reported. This study aimed to explore the expression, clinicopathological features, diagnostic, and prognostic values of DiGeorge syndrome critical region gene 5 in ovarian cancer. The total levels of DiGeorge syndrome critical region gene 5 transcript variant 1 (NR_002733.2) and 2 (NR_045121.1) in patients with ovarian cancer were determined by quantitative reverse transcription polymerase chain reaction. The correlation of DiGeorge syndrome critical region gene 5 expression with clinicopathological factors was statistically analyzed by χ2 test. Overall survival analysis was carried out with the Kaplan–Meier curves with the log-rank test. Univariate and multivariate Cox regression analyses were performed to identify the prognostic significance of DiGeorge syndrome critical region gene 5 expression. Receiver operating characteristic curves were constructed to estimate the diagnostic and prognostic usefulness of DiGeorge syndrome critical region gene 5 in ovarian cancer. Results showed that relative DiGeorge syndrome critical region gene 5 expression was reduced by 36.81% and 65.79% in ovarian cancer tissues of patients and Gene Expression Omnibus DataSets (GSE119056) in contrast to normal tissues, respectively. Patients with lymph node metastasis and distant metastasis exhibited lower levels of DiGeorge syndrome critical region gene 5 in contrast to those patients with non-lymph node metastasis and non-distant metastasis, respectively. Low expression of DiGeorge syndrome critical region gene 5 was significantly associated with large tumor size, more lymph node metastasis, present distant metastasis, advanced clinical stage, and short overall survival in patients with ovarian cancer. Low expression of DiGeorge syndrome critical region gene 5 was an independent unfavorable prognostic factor for overall survival in patients with ovarian cancer. Receiver operating characteristics curves for prognosis yielded significant area under curves for lymph node metastasis, clinical stage, and overall survival. In conclusion, our study demonstrated that downregulated DiGeorge syndrome critical region gene 5 may be a new promising biomarker for predicting clinical progression and prognosis in patients with ovarian cancer.


Sign in / Sign up

Export Citation Format

Share Document