scholarly journals Serum exosomal miR-4787-3p as potential lymph node metastasis and prognostic marker in esophageal squamous cell carcinoma.

2021 ◽  
Author(s):  
Shuang Liu ◽  
Zheng Lin ◽  
Jianwen Wang ◽  
Zerong Zheng ◽  
Wenqing Rao ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cox Regression ◽  
High Serum ◽  
Migration And Invasion ◽  
Cox Regression Analysis ◽  
Mirna Array ◽  
Node Metastasis

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

scholarly journals CXCR7 promotes migration and invasion in head and neck squamous cell carcinoma by upregulating TGF-β1/Smad2/3 signaling

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Nayoung Kim ◽  
Hyewon Ryu ◽  
Solbi Kim ◽  
Mina Joo ◽  
Heung Jin Jeon ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Migration And Invasion ◽  
Node Metastasis ◽  
Tgf Β1

AbstractThe chemokine receptor CXCR7 has been suggested to play important roles in the progression of several types of cancers. However, few studies have investigated the biological roles of CXCR7 in head and neck squamous cell carcinoma (HNSCC). CXCR7 expression and its clinical implications were examined in 103 HNSCC tissues using immunohistochemistry (IHC). The biological roles and mechanisms of CXCR7-mediated signaling pathways were investigated in HNSCC cells through CXCR7 overexpression in vitro and in vivo. High expression of CXCR7 was significantly associated with tumor size (P = 0.007), lymph node metastasis (P = 0.004), and stage (P = 0.020) in HNSCC. Overexpression of CXCR7 in HNSCC cells enhanced cell migration and invasion in vitro and promoted lymph node metastasis in vivo. CXCR7 also induced epithelial–mesenchymal transition through PI3K/AKT. CXCR7 increased secretion of transforming growth factor-β1 (TGF-β1) and promoted EMT through phosphorylated Smad2/3. Taken together, our results provide functional and mechanistic roles of CXCR7 as a master regulator of oncogenic TGF-β1/Smad2/3 signaling in HNSCC, suggesting that CXCR7 might be a therapeutic target for the treatment of HNSCC.

scholarly journals Endoscopic Versus Surgical Therapy for Early Esophagogastric Junction Adenocarcinoma Based on Lymph Node Metastasis Risk: A Population-Based Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Hua Ye ◽  
Ping Chen ◽  
Yi-Fan Wang ◽  
Xiu-Jun Cai
Keyword(s):  
Regression Analysis ◽  
Lymph Node ◽  
Tumor Size ◽  
Esophagogastric Junction ◽  
Cox Regression ◽  
Radical Surgery ◽  
Early Stage ◽  
Cox Regression Analysis ◽  
Node Metastasis ◽  
Poor Differentiation

BackgroundIn this study, we aimed to compare the prognosis and lymph node metastasis (LNM) risk in patients with early-stage esophagogastric junction (EGJ) adenocarcinoma after endoscopic treatment (ET) or radical surgery.MethodsWe collected data from eligible patients based on the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016. Logistic regression analysis was used to determine independent predictors of LNM (examination of at least 16 lymph nodes). Cox regression analysis and propensity score-matched (PSM) analysis were subsequently utilized to compare the overall survival (OS) and cancer-specific survival (CSS) of patients treated with ET or radical surgery.ResultsIn total, 3708 patients were identified. Among them, 856 patients had greater than or equal to 16 examined lymph nodes (LNs) (LNE≥16). The LNM rates were 18.8% in all patients 8.3% in T1a patients and 24.6% in T1b patients. Independent predictors of LNM were submucosal invasion, tumor size ≥3cm and decreasing differentiation (P<0.05). The LNM rate decreased to approximately 5.3% in T1b tumors with well differentiation and tumor size <3cm. However, the LNM incidence increased to 17.9% or 33.3% in T1a tumors with poor differentiation or with both tumor size≥3cm and poor differentiation. Cox regression analysis demonstrated CSS was not significantly different in early-stage EGJ adenocarcinoma patients undergoing ET and those treated with radical surgery (HR= 1.004, P=0.974), which were robustly validated after PSM analysis. Moreover, subgroup analysis stratified by T1a and T1b showed similar results.ConclusionsThe findings of this study indicated ET as an alternative to radical surgery in early EGJ adenocarcinoma.

scholarly journals Follistatin-Like 3 Correlates With Lymph Node Metastasis and Serves as a Biomarker of Extracellular Matrix Remodeling in Colorectal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Chao Yang ◽  
Fengyu Cao ◽  
Shuoyang Huang ◽  
Yongbin Zheng
Keyword(s):  
Colorectal Cancer ◽  
Extracellular Matrix ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Protein Level ◽  
Cox Regression ◽  
External Validation ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis ◽  
Node Metastasis

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.

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
Keyword(s):  
Ovarian Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cyclin D1 ◽  
Cox Regression ◽  
Cancer Tissue ◽  
Tissue Samples ◽  
Cox Regression Analysis ◽  
Node Metastasis ◽  
Incidence And Mortality

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.

scholarly journals Development and Validation of Prognostic Nomogram for Primary Peritoneal Serous Carcinoma Compared With FIGO Staging System: A Population-Based Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Ming Chen ◽  
Zhenzhen Wen ◽  
Zhengwei Qi ◽  
Min Gao
Keyword(s):  
Prognostic Factors ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cox Regression ◽  
Staging System ◽  
Serous Carcinoma ◽  
Cox Regression Analysis ◽  
Node Metastasis ◽  
Figo Staging ◽  
Gynecology And Obstetrics

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.

Development and validation of a six-gene signature for predicting prognosis in prostate cancer patients with lymph node metastasis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17524-e17524
Author(s):  
Jinan Guo ◽  
Wenzhuan Xie ◽  
Mengli Huang ◽  
Chan Gao
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Lymph Node Metastasis ◽  
Cox Regression ◽  
Risk Group ◽  
Gene Signature ◽  
High Risk Group ◽  
Wild Type ◽  
Cox Regression Analysis ◽  
Node Metastasis

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.

scholarly journals Positive ALDH1A3 and Negative GPX3 Expressions Are Biomarkers for Poor Prognosis of Gallbladder Cancer

2013 ◽  
Vol 35 ◽  
pp. 163-172 ◽  
Author(s):  
Zhu-lin Yang ◽  
Leping Yang ◽  
Qiong Zou ◽  
Yuan Yuan ◽  
Jinghe Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
Regression Analysis ◽  
Lymph Node ◽  
Gallbladder Cancer ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Prognostic Predictor ◽  
Node Metastasis ◽  
Kaplan Meier

Background. Gallbladder cancers (GBCs) are highly aggressive cancers with high mortality. However, biological markers for the progression and prognosis of GBC are currently unavailable in the clinic.Objective. To identify biomarkers for predicting GBC metastasis and prognosis.Methods. We examined ALDH1A3 and GPX3 expressions in 46 squamous cell/adenosquamous carcinomas (SC/ASC) and 80 adenocarcinomas (AC) by using immunohistochemistry.Results. Positive ALDH1A3 and negative GPX3 expressions were significantly associated with lymph node metastasis and invasion of SC/ASCs and ACs. Univariate Kaplan-Meier analysis showed that either positive ALDH1A3(P<0.001)or negative GPX3(P<0.001)expression significantly correlated with decreased overall survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that positive ALDH1A3 expression or negative GPX3 expression was an independent poor-prognostic predictor in both SC/ASC and AC patients.Conclusions. Our study suggested that positive ALDH1A3 and negative GPX3 expressions are closely associated with clinical pathological behaviors and poor prognosis of gallbladder cancer.

Endoscopic versus surgical therapy for early esophagogastric junction adenocarcinoma based on lymph node metastasis risk：a population-based analysis

2021 ◽  
Author(s):  
Hua Ye ◽  
Ping Chen ◽  
yi-fan Wang ◽  
Xiu-Jun Cai
Keyword(s):  
Regression Analysis ◽  
Lymph Node ◽  
Tumor Size ◽  
Esophagogastric Junction ◽  
Cox Regression ◽  
Radical Surgery ◽  
Early Stage ◽  
Cox Regression Analysis ◽  
Node Metastasis ◽  
Poor Differentiation

Abstract Background In this study, we aimed to compare the prognosis and lymph node metastasis (LNM) risk in patients with early-stage esophagogastric junction (EGJ) adenocarcinoma after endoscopic treatment (ET) or radical surgery. Methods We collected data from eligible patients based on Surveillance, Epidemiology, and End Results database between 2004 and 2016. Logistic regression analysis was used to determine independent predictors of LNM (examination of at least 16 lymph nodes). Cox regression analysis and propensity score-matched (PSM) analysis were subsequently utilized to compare overall survival (OS) and cancer-specific survival (CSS) of patients treated with ET or radical surgery . Results In total, 5266 patients were identified. Among them, 856 patients had greater than or equal to 16 examined lymph nodes (LNs) (LNE ≥ 16). The LNM rates were 18.8% in: all patients 8.3% in T1a patients and 24.6% in T1b patients. Independent predictors of LNM were submucosal invasion, tumor size ≥ 3cm and decreasing differentiation (P < 0.05). The LNM rate decreased to approximately 5.3% in T1b tumors with well differentiation and tumor size < 3cm. However, the LNM incidence increased to 17.9% or 33.3% in T1a tumors with poor differentiation or with both tumor size ≥ 3cm and poor differentiation. Cox regression analysis demonstrated CSS was not significantly different in early-stage EGJ adenocarcinoma patients undergoing ET and those treated with radical surgery (HR = 0.830, P = 0.062), which were robustly validated after PSM analysis. Moreover, subgroup analysis stratified by T1a and T1b showed similar results. Conclusions Consequently, our findings indicated ET as an alternative to radical surgery in early EGJ adenocarcinoma.

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