scholarly journals Prognostic and Clinicopathological Significance of MUC Family Members in Colorectal Cancer: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-16
Author(s):  
Chao Li ◽  
Didi Zuo ◽  
Tao Liu ◽  
Libin Yin ◽  
Chenyao Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Protective Effect ◽  
Clinicopathological Characteristics ◽  
Cochrane Library ◽  
Muc1 Expression ◽  
Free Survival ◽  
Expression Levels ◽  
Muc2 Expression ◽  
High Level

Objective. To assess the association between MUC expression levels in colorectal cancer (CRC) tissues and prognosis and investigate the associations between MUC expression levels and CRC clinicopathological characteristics. Methods. The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception through September 13, 2019, to identify studies investigating the association between MUC expression levels in CRC tissues and prognosis. Pooled hazard ratios (HRs) or odds ratio (ORs) with 95% confidence intervals (CIs) were used to evaluate associations between MUC expression levels and prognosis or clinicopathological characteristics, respectively. The heterogeneity between studies was assessed by the I2 values, whereas the likelihood of publication bias was assessed by Egger’s linear regression and Begg’s rank correlation test. Results. Among 33 included studies (n=6032 patients), there were no associations between combined MUC phenotype expression levels and overall survival (OS) or disease-free survival (DFS)/relapse-free survival (RFS) in patients with CRC. In subgroup analyses, the upregulated MUC1 expression (HR=1.50; 95% CI, 1.29–1.74; P<0.00001) was associated with poor OS. However, the upregulated MUC2 expression (HR=0.64; 95% CI, 0.52–0.79; P<0.00001) was associated with better OS. Furthermore, a high level of MUC1 expression (HR=1.99; 95% CI, 0.99–3.99; P=0.05) was associated with shorter DFS/RFS. However, patients with a low level of MUC2 tumors showed better DFS/RFS than patients with a high level of MUC2 tumors (HR=0.71; 95% CI, 0.49–1.04; P=0.08; P=0.0.009, I2=67%) and MUC5AC expression (HR=0.56; 95% CI, 0.38–0.82; P=0.003) was associated with longer DFS/RFS. In addition, a high level of MUC1 expression was associated with CRC in the rectum, deeper invasion, lymph node metastasis, distant metastasis, advanced tumor stage, and lymphatic invasion. A high level of MUC2 expression had a protective effect. High secretion of MUC5AC is associated with colon cancer compared with rectal cancer. Conclusion. The protein expression of MUC1 might be a poor biomarker in colorectal cancer and might play a role in tumor transformation and metastasis. However, the protein expression of MUC2 expression might have a protective effect. Furthermore, randomized controlled trials (RCTs) of large patients are needed to confirm the results.

scholarly journals Prognostic Value of MUC2 Expression in Colorectal Cancer: A Systematic Review and Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Chao Li ◽  
Didi Zuo ◽  
Libin Yin ◽  
Yuyang Lin ◽  
Chenguang Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Expression Level ◽  
Cochrane Library ◽  
Depth Of Invasion ◽  
Poor Prognostic Factor ◽  
Free Survival ◽  
Expression Levels ◽  
Muc2 Expression

Background. The reliability of MUC2 as a prognostic marker in colorectal cancer (CRC) is controversial. This study evaluated the association between MUC2 expression levels in CRC tissues and prognosis. Methods. The PubMed, Web of Science, Embase, Cochrane Library, China Biology Medicine disc (CBMdisc), Wanfang Database, and China National Knowledge Infrastructure (CNKI) databases were searched to identify studies exploring the relationship between MUC2 expression in CRC tissues and overall survival (OS). Pooled hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs) were used to evaluate the associations between MUC2 expression levels and prognosis and MUC2 expression levels and CRC clinicopathological characteristics, respectively. Results. The meta-analysis included 11 studies (2619 patients). Low MUC2 expression level was significantly associated with poor OS (HR, 1.67; 95% CI, 1.43–1.94; P<0.00001) and disease-free survival (DFS)/recurrence-free survival (RFS) (HR, 1.60; 95% CI, 1.21–2.12; P=0.001) in patients with CRC. Low MUC2 expression level was associated with advanced TNM stage (RR, 1.42; 95% CI, 1.26–1.60; P<0.00001), lymph node metastasis (RR, 1.41; 95% CI, 1.25–1.60; P<0.00001), lymphatic invasion (RR,1.64; 95% CI, 1.26–2.12; P=0.0002), rectal tumor site (RR, 1.26; 95% CI, 1.09–1.46; P=0.001), and large tumor size (RR,1.32; 95% CI, 1.02–1.70; P=0.03). There were no associations between low MUC2 expression level and gender, histological grade, depth of invasion, and distant metastasis. Conclusion. The low levels of MUC2 in CRC tissues are poor prognostic factor independent of stage or other well-recognized markers of later-stage disease. Large well-designed cohort studies are required to validate MUC2 as a biomarker for poor prognosis in CRC.

scholarly journals Neonatal Nav1.5 Protein Expression in Human Colorectal Cancer: Immunohistochemical Characterization and Clinical Evaluation

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3832
Author(s):  
Elena Lastraioli ◽  
Scott P. Fraser ◽  
R. Mine Guzel ◽  
Jessica Iorio ◽  
Lapo Bencini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Expression Patterns ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Normal Mucosa ◽  
Free Survival ◽  
Human Carcinomas ◽  
Clinical Biomarker ◽  
High Level

Voltage-gated Na+ channels (VGSCs) are expressed widely in human carcinomas and play a significant role in promoting cellular invasiveness and metastasis. However, human tissue-based studies and clinical characterization are lacking. In several carcinomas, including colorectal cancer (CRCa), the predominant VGSC is the neonatal splice variant of Nav1.5 (nNav1.5). The present study was designed to determine the expression patterns and clinical relevance of nNav1.5 protein in human CRCa tissues from patients with available clinicopathological history. The immunohistochemistry was made possible by the use of a polyclonal antibody (NESOpAb) specific for nNav1.5. The analysis showed that, compared with normal mucosa, nNav1.5 expression occurred in CRCa samples (i) at levels that were significantly higher and (ii) with a pattern that was more delineated (i.e., apical/basal or mixed). A surprisingly high level of nNav1.5 protein expression also occurred in adenomas, but this was mainly intracellular and diffuse. nNav1.5 showed a statistically significant association with TNM stage, highest expression being associated with TNM IV and metastatic status. Interestingly, nNav1.5 expression co-occurred with other biomarkers associated with metastasis, including hERG1, KCa3.1, VEGF-A, Glut1, and EGFR. Finally, univariate analysis showed that nNav1.5 expression had an impact on progression-free survival. We conclude (i) that nNav1.5 could represent a novel clinical biomarker (‘companion diagnostic’) useful to better stratify CRCa patients and (ii) that since nNav1.5 expression is functional, it could form the basis of anti-metastatic therapies including in combination with standard treatments.

scholarly journals YY1 Silencing Induces 5-Fluorouracil-Resistance and BCL2L15 Downregulation in Colorectal Cancer Cells: Diagnostic and Prognostic Relevance

2021 ◽  
Vol 22 (16) ◽  
pp. 8481
Author(s):  
Silvia Vivarelli ◽  
Luca Falzone ◽  
Saverio Candido ◽  
Benjamin Bonavida ◽  
Massimo Libra
Keyword(s):  
Colorectal Cancer ◽  
Response To Therapy ◽  
Advanced Stage ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Expression Levels ◽  
Single Cell Sequencing ◽  
Yin Yang 1 ◽  
Anti Cancer ◽  
Colorectal Cancer Cells

Colorectal cancer (CRC) is characterized by genetic heterogeneity and is often diagnosed at an advanced stage. Therefore, there is a need to identify novel predictive markers. Yin Yang 1 (YY1) is a transcription factor playing a dual role in cancer. The present study aimed to investigate whether YY1 expression levels influence CRC cell response to therapy and to identify the transcriptional targets involved. The diagnostic and prognostic values of YY1 and the identified factor(s) in CRC patients were also explored. Silencing of YY1 increased the resistance to 5-Fluorouracil-induced cytotoxicity in two out of four CRC cells with different genotypes. BCL2L15/Bfk pro-apoptotic factor was found selectively expressed in the responder CRC cells and downregulated upon YY1 knockdown. CRC dataset analyses corroborated a tumor-suppressive role for both YY1 and BCL2L15 whose expressions were inversely correlated with aggressiveness. CRC single-cell sequencing dataset analyses demonstrated higher co-expression levels of both YY1 and BCL2L15 within defined tumor cell clusters. Finally, elevated levels of YY1 and BCL2L15 in CRC patients were associated with larger relapse-free survival. Given their observed anti-cancer role, we propose YY1 and BCL2L15 as candidate diagnostic and prognostic CRC biomarkers.

The Effect of High CDC6 Levels on Predicting Poor Prognosis in Colorectal Cancer

Chemotherapy ◽  
2022 ◽  
pp. 1-10
Author(s):  
Cheng Yang ◽  
Na Xie ◽  
Zhifei Luo ◽  
Xiling Ruan ◽  
Yixin Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Poor Prognosis ◽  
Cancer Metastasis ◽  
Mrna Level ◽  
Normal Mucosa ◽  
Tnm Stage ◽  
Expression Levels ◽  
Normal Tissues

<b><i>Introduction:</i></b> We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC). <b><i>Methods:</i></b> CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry. <b><i>Results:</i></b> Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time. <b><i>Conclusion:</i></b> CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.

scholarly journals Prognostic roles of microRNA 143 and microRNA 145 in colorectal cancer: A meta-analysis

2019 ◽  
Vol 34 (1) ◽  
pp. 6-14 ◽  
Author(s):  
Chenyao Li ◽  
Guoqiang Yan ◽  
Libin Yin ◽  
Tao Liu ◽  
Chao Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Hazard Ratio ◽  
High Expression ◽  
Cochrane Library ◽  
Event Free Survival ◽  
Free Survival ◽  
High Event ◽  
Low Expression

Background: A systematic analysis was conducted to clarify the relationship between miR-143/145 and the prognosis of colorectal cancer. Materials and methods: We searched four databases: PubMed, EMBASE, Web of Science, and the Cochrane Library. We extracted and estimated the hazard ratios for survival outcomes, which compared low and high expression levels of miR-143/145 in colorectal cancer patients in the available studies. Each individual hazard ratio was used to calculate the pooled hazard ratio. Results: A total of 17 articles including 5128 patients were ultimately included. The results showed that there was no significant difference between low expression and high expression of miR-143 in the overall survival of colon cancer patients. However, low expression of miR-143 was significantly associated with high event-free survival (hazard ratio (HR) 0.6; 95% confidence interval (CI) 0.40, 0.88). Low expression of miR-145 was associated with poor prognosis of patients (HR 1.92; 95% CI 1.45, 2.54); those with low expression of miR-145 were at 1.92-fold higher risk for short-term overall survival than those with high expression of miR-145. MiR-145 was an unfavorable factor for the prognosis of colorectal cancer. There were no significant differences between low expression of miR-145 and high expression of miR-143 in event-free survival. Conclusion: miR-143 and miR-145 have promising prognostic value for colorectal cancer. Low expression of miR-143 can predict high event-free survival, and low expression of miR-145 can predict poor overall survival.

scholarly journals Proinflammatory and Anti-Inflammatory Cytokines Mediated by NF-κB Factor as Prognostic Markers in Mammary Tumors

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Gustavo Rodrigues Martins ◽  
Gabriela Bottaro Gelaleti ◽  
Marina Gobbe Moschetta ◽  
Larissa Bazela Maschio-Signorini ◽  
Debora Ap. Pires de Campos Zuccari
Keyword(s):  
Protein Expression ◽  
Survival Time ◽  
Inflammatory Cytokines ◽  
Prognostic Markers ◽  
Tumor Development ◽  
Mammary Tumors ◽  
Clinicopathological Characteristics ◽  
Expression Levels ◽  
Gene And Protein Expression ◽  
High Gene

Inflammation results in the production of cytokines, such as interleukin- (IL-) 4 and IL-10 with immunosuppressive properties or IL-6 and TNF-αwith procarcinogenic activity. Furthermore, NF-κB is the major link between inflammation and tumorigenesis. This study verified the interaction between active inflammatory cytokines in the tumor microenvironment and serum of female dogs with mammary tumors and their correlation with the clinicopathological characteristics and overall survival. Measurement of gene expression was performed by qPCR and protein levels by ELISA/Luminex. High gene and protein expression levels of NF-κB, IL-6, and TNF-αwere found in association with characteristics that reflect worse prognosis and a negative correlation between TNF-αprotein expression and survival time was observed (p<0.05). In contrast, high gene and protein expression levels of IL-4 and IL-10 were associated with characteristics of better prognosis and an increased level of IL-4 and a longer survival time of animals were obtained (p<0.05). In addition, there was a positive correlation between TNF-αand IL-6 expression in association with NF-κB. The results show a significant correlation of these cytokines with tumor development, associated with NF-κB expression and cytokines promodulation, showing that these biological factors could be used as predictive and prognostic markers in breast cancer.

Down-regulation of KRAS-interacting miRNA-143 to predict prognosis and response to EGFR-targeted agents in colorectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14066-e14066
Author(s):  
Florian Eisner ◽  
Michael Stotz ◽  
Hellmut Samonigg ◽  
Sigurd Lax ◽  
Gerald Hoefler ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Targeted Therapy ◽  
Objective Response ◽  
Progression Free Survival ◽  
Targeted Agents ◽  
Wild Type ◽  
Down Regulation ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Expression Levels

e14066 Background: MicroRNA-143 is frequently down-regulated in colorectal cancer (CRC) and influence CRC cell proliferation, apoptosis and sensitivity to 5-fluorouracil. mRNA encoded by the KRAS oncogene has been identified as a target of microRNA-143. However, the prognostic significance of microRNA-143 expression and the ability to predict the patient response to EGFR-targeted agents have not been explored yet. Methods: In this study, we analyzed 77 CRC harboring wild-type KRAS and obtaining treatment with the EGFR-targeting monoclonal antibodies cetuximab or panitumumab. MicroRNA-143 expression was measured by RT-PCR in both CRC and corresponding non-neoplastic colon tissue and the expression levels were correlated with clinico-pathological characteristics. Cancer-specific survival was calculated by uni- and multivariate analyses. The progression-free survival and objective response rates on EGFR-targeted therapy were also evaluated. Results: Down-regulation of microRNA-143 was observed in 47/77 (61%) CRC. Multivariate Cox regression analysis identified low levels of microRNA-143 expression as an independent prognostic factor with respect to cancer-specific survival (HR=1.92, CI=1.1-3.4, p=0.024). A significant difference was observed with respect to progression-free survival on EGFR-targeted therapy (p=0.031, log-rank test), but there were no significant differences with regard to the objective response rate. Conclusions: Our data suggest that microRNA-143 expression levels serve as independent prognostic biomarker for KRAS wild-type CRC patients but not as predictor for EGFR-targeted therapy. In addition, we consider microRNA-143 as a potential drug target for future therapy of CRC.

scholarly journals Galectin-3 expression in colorectal cancer and its correlation with clinical pathological characteristics and prognosis

Open Medicine ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 226-230 ◽  
Author(s):  
Liu Tao ◽  
Li Jin ◽  
Li Dechun ◽  
Yang Hongqiang ◽  
Kou Changhua ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Cancer Patients ◽  
Biological Marker ◽  
Progression Free Survival ◽  
Survival Times ◽  
Expression Levels ◽  
Galectin 3 ◽  
Colorectal Cancer Patients ◽  
Cancer Tissues

AbstractObjectiveTo explore the expression levels of galectin-3 in colorectal cancer and the association between galectin-3 and its clinical pathological parameters, as well as the prognosis of colorectal cancer patients.MethodsAn immunohistochemistry assay was used to test the expression levels of galectin-3 in cancer tissues of 61 colorectal cancer cases and in normal intestinal tissues adjacent to the cancer tissues of 23 cases. The associations between protein expression levels of galectin-3 and the clinicopathological features, such as age, sex, pathology type, lymphatic metastasis, and prognosis were also analyzed.ResultsThe positive rate of galectin-3 in cancer tissues was significantly higher than that of cancer-adjacent tissues: 62.5% (38/61) versus 13.0% (3/23) (P<0.05), respectively. Correlation was found between the protein expression of galectin-3 and the tumor size (P<0.05), as well as between the tumor differentiation (P<0.05) and Duke staging (P<0.05). The median progression-free survival times of patients with galectin-3 positive and negative expression were 19.2 and 35.1 months, respectively, with significant statistical difference (P<0.05).ConclusionGalectin-3 expression was correlated with the genesis and development of colorectal cancer and which could be used a biological marker for the prognosis of colorectal cancer patients.

scholarly journals Prognostic value of α2δ1 in hypopharyngeal carcinoma: A retrospective study

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 1395-1402
Author(s):  
Qiang Liu ◽  
Yanbo Dong ◽  
Shuoqing Yuan ◽  
Minghang Yu ◽  
Liangfa Liu ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Clinicopathological Characteristics ◽  
Hypopharyngeal Carcinoma ◽  
Free Survival ◽  
Expression Levels ◽  
Normal Tissues ◽  
Voltage Dependent ◽  
Tumor Types

Abstract Voltage-dependent calcium channel subunit alpha-2/delta-1 (α2δ1) has been identified as a marker of cancer stem cells in multiple malignant tumor types. However, α2δ1’s role in the prognosis of hypopharyngeal squamous cell carcinoma (HSCC) was not reported. In our study, ten pairs of HSCC and peritumoral normal tissues were used for immunohistochemistry assessment. And α2δ1 expression levels of 34 more HSCC samples were also evaluated, represented by the integral optic density using Image-Pro Plus. Clinicopathological associations and prognostic value of α2δ1 were analyzed. As a result, α2δ1 expression was frequently increased in HSCC tissues. Although the correlation between patients’ clinicopathological characteristics and their α2δ1 expression levels was not significant, α2δ1 expression was significantly correlated with unfavorable overall survival (OS) (P = 0.018) and progression-free survival (PFS) (P = 0.023). Univariate and multivariate cox regression analyses suggested α2δ1’s prognostic role for both OS and PFS (P = 0.013 and 0.011, respectively). This study specifically demonstrated that α2δ1 regularly increased in HSCC compared with peritumoral tissues, and α2δ1 could act as a promising prognostic marker in HSCC patients.

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