LncRNA PCAT6 as a Predictor of Poor Colorectal Cancer Patient Prognosis: A TCGA Dataset Analysis

2021 ◽  
Author(s):  
Lin Han ◽  
Yanjun Sun ◽  
Dengqun Sun
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Gene Silencing ◽  
Patient Survival ◽  
Rectal Adenocarcinoma ◽  
Gene Set Enrichment Analysis ◽  
Survival Outcomes ◽  
Cancer Type ◽  
Regression Analyses ◽  
Clinicopathological Findings

Abstract Background: The long non-coding RNA (lncRNA)) PCAT6 has been studied in many cancers, yet its relationship with colorectal cancer (CRC) remains poorly defined. Here, we conducted an analysis of The Cancer Genome Atlas (TCGA) database to better clarify the role of PCAT6 in this cancer type.Materials and Methods: Wilcoxon rank-sum tests were utilized to assess relative levels of PCAT6 in CRC tumors and normal tissues, while logistic regression analyses were utilized to compare the relationships between PCAT6 levels and clinicopathological findings. Kaplan-Meier curves and Cox regression analyses were used to gauge correlations between PCAT6 and patient survival outcomes, while the biological roles of this lncRNA were investigated via a gene set enrichment analysis (GSEA) approach.Results: PCAT6 levels were significantly correlated with CRC patient N stage (OR = 1.8 for N1&N2 vs. N0), lymphatic invasion (OR = 1.9 for Yes vs. No), M stage (OR = 2.1 for M1 vs. M0), CEA level (OR = 1.9 for >5 vs. ≤5), perineural invasion (OR = 1.9 for Yes vs. No), pathologic stage (OR = 1.9 for Stage IIIIV vs. Stage I/II), and neoplasm type (OR = 2.1 for rectal adenocarcinoma vs. colon adenocarcinoma) (all P < 0.05). CRC patients expressing higher PCAT6 levels exhibited poorer survival outcomes than those expressing low levels of this lncRNA (P = 0.017), and in univariate analyses, higher PCAT6 levels were linked to worse overall survival (OS) (HR = 1.540; 95% CI: 1.079-2.1997; P = 0.017), with this relationship also being preserved in a multivariate analysis (HR = 6.892; 95% CI: 1.713-27.727, P = 0.007). GSEA revealed high PCAT6 expression to be linked to differential DNA methylation enrichment, with high PCAT6 levels being associated with changes in base excision repair, cellular senescence, G2 M DNA damage checkpoint, chromatin-modifying enzyme, and gene silencing by RNA activity. Conclusions: PCAT6 represents a promising prognostic biomarker of poor CRC patient survival outcomes, with DNA methylation and RNA-mediated gene silencing being potentially promising mechanistic pathways whereby this lncRNA may shape patient outcomes.

scholarly journals CEND1 and GJB6 co-expression as a prognostic factor in colorectal cancer

2021 ◽  
Author(s):  
Rui Chen ◽  
Zhan Wang ◽  
Dong Ma ◽  
Yijiang Han ◽  
Junsong Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Perineural Invasion ◽  
Patient Survival ◽  
Colorectal Cancer Patient ◽  
Cell Communication ◽  
Tumor Location ◽  
Protein Levels ◽  
Kaplan Meier ◽  
Clinicopathological Findings

Abstract Background: Perineural invasion is an important mechanism of cancer progression that is not well understood at present. The present study explored the relationship between GJB6, CEND1, and cell-cell communication as regulators of colorectal cancer patient survival and clinicopathological findings.Method: Immunohistochemical staining was performed to assess CEND1 and GJB6 expression levels in CRC patient samples, while survival outcomes were assessed using Kaplan-Meier curves and log-rank tests.Results: Elevated CEND1 expression was associated with tumor location, poor differentiation, and perineural invasion, while GJB6 expression was positively correlated with TNM stage, distant metastasis, and perineural invasion. In addition, GJB6 and CEND1 protein levels were correlated with one another in CRC patient tissues, and high expression of both of these proteins was associated with a higher risk of perineural invasion. CEND1+/GJB6+ status was also associated with poorer patient survival, highlighting both of these proteins as prognostic biomarkers in CRC patients.Conclusion: Elevated levels of CEND1 and GJB6 are independent predictors of poorer CRC patient prognosis.

Neutrophil to Leukocyte Ratio Correlates to Patient Survival Outcomes in Colorectal Cancer

2015 ◽  
Vol 110 ◽  
pp. S563-S564
Author(s):  
Shahrooz Rashtak ◽  
Xiaoyang Ruan ◽  
Hongfang Liu ◽  
Russell Vanderboom ◽  
Jill Washechek Aleto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Patient Survival ◽  
Survival Outcomes

scholarly journals Impact of Colon-Specific DNA Methylation-Regulated Gene Modules on Colorectal Cancer Patient Survival

2019 ◽  
Vol 25 ◽  
pp. 3549-3557 ◽  
Author(s):  
Haitao Yu ◽  
Wei Jiang ◽  
Gang Chen ◽  
Fan Yang ◽  
Xingwang Zhao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Cancer Patient ◽  
Patient Survival ◽  
Colorectal Cancer Patient ◽  
Gene Modules

scholarly journals Critical Role of Histone Methylation in Tumor Suppressor Gene Silencing in Colorectal Cancer

2003 ◽  
Vol 23 (1) ◽  
pp. 206-215 ◽  
Author(s):  
Yutaka Kondo ◽  
LanLan Shen ◽  
Jean-Pierre J. Issa
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Dna Methylation ◽  
Gene Silencing ◽  
Dna Methyltransferase ◽  
Critical Role ◽  
Histone H3 ◽  
Suppressor Gene ◽  
Promoter Dna Methylation ◽  
Promoter Dna

ABSTRACT The mechanism of DNA hypermethylation-associated tumor suppressor gene silencing in cancer remains incompletely understood. Here, we show by chromatin immunoprecipitation that for three genes (P16, MLH1, and the O 6-methylguanine-DNA methyltransferase gene, MGMT), histone H3 Lys-9 methylation directly correlates and histone H3 Lys-9 acetylation inversely correlates with DNA methylation in three neoplastic cell lines. Treatment with the histone deacetylase inhibitor trichostatin A (TSA) resulted in moderately increased Lys-9 acetylation at silenced loci with no effect on Lys-9 methylation and minimal effects on gene expression. By contrast, treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5Aza-dC) rapidly reduced Lys-9 methylation at silenced loci and resulted in reactivation for all three genes. Combined treatment with 5Aza-dC and TSA was synergistic in reactivating gene expression through simultaneous effects on Lys-9 methylation and acetylation, which resulted in a robust increase in the ratio of Lys-9 acetylated and methylated histones at loci showing dense DNA methylation. By contrast to Lys-9, histone H3 Lys-4 methylation inversely correlated with promoter DNA methylation, was not affected by TSA, and was increased moderately at silenced loci by 5Aza-dC. Our results suggest that reduced H3 Lys-4 methylation and increased H3 Lys-9 methylation play a critical role in the maintenance of promoter DNA methylation-associated gene silencing in colorectal cancer.

scholarly journals A Mechanistic Investigation of the Relationship Between Extramural Vascular Invasion (EMVI) and CpG Island Methylator Phenotype (CIMP) in Rectal Cancer

2021 ◽  
Author(s):  
◽  
Rory Kokelaar
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Rectal Cancer ◽  
Vascular Invasion ◽  
Survival Outcomes ◽  
Potential Biomarker ◽  
Mechanistic Investigation ◽  
Rectal Cancers

Colorectal cancer (CRC) is the third most frequent cancer and the second leading cause of cancer death worldwide. Each year, one million people will develop CRC, and 40-50% will die within five years. Furthermore, rectal and distal sigmoid cancers are known to present at a later stage and have a poorer prognosis than other colonic cancers. Rectal cancers that demonstrate pathological extramural vascular invasion (EMVI-positive) are known to have a poorer prognosis than those that do not (EMIV-negative), and EMVI has is acknowledged as an important risk factor for systemic recurrence, local recurrence and death. Additionally, EMVI status influences the need for pre- and post-operative chemoradiation (CRT); which may influence survival outcomes. Aberrant DNA methylation is emerging as a carcinogenic mechanism and potential biomarker in colorectal cancer. This study investigates the association between hypermethylation and EMVI in vivo and in vitro. Firstly, the in vivo associations between hypermethylation, EMVI, and clinical and histopathological outcomes are examined. Secondly, an investigation of the effects of demethylation on invasive colorectal cell lines in vitro aims to illuminate the genetic and cellular mechanisms that underlie methylation-dependent pathological cellular behaviour. Finally, highlighted biologic mechanisms are investigated in vivo to discover if there is an association with EMVI and survival outcomes. By these means the axis of association between hypermethylation, EMVI, and clinical outcomes is investigated. The investigation is conducted within the framework of consensus molecular subtyping in colorectal cancer, and in concordance with current methodologies of assessing DNA methylation status. The primary findings demonstrate that EMVI is associated with hypermethylation in vivo, but that there is no direct correlation between hypermethylation and disease-free (DFS) or overall survival (OS). In vitro, demethylation of hypermethylated colorectal cancer cells, by means of established demethylating agent 5-azacytidine and putative demethylator RRx-001, reduces their propensity to migrate and invade. Demethylation in vitro is also associated with changes in the expression of the metalloproteinases involved in the metabolism of the basement membrane and the epithelial-to-mesenchymal transition and tumour metastasis, notably MMP2 and TIMP2. Changes in expression were confirmed at transcriptomal and proteomic levels in response to demethylation. In vivo, MMP2 expression was shown to be statistically significantly associated with EMVI, DFS, and OS, and was also independently predictive of EMVI, raising the possibility that it could act as a diagnostic and predictive biomarker in rectal cancers. These findings indicate a mechanistic association between hypermethylation and EMVI, mediated by methylation-dependent expression of metalloproteinases. Metalloproteinase expression, specifically MMP2, may act as a potential biomarker for EMVI and correlates to survival outcomes in rectal cancer.

scholarly journals Interrogation of gender disparity uncovers androgen receptor as the transcriptional activator for oncogenic miR-125b in gastric cancer

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Ben Liu ◽  
Meng Zhou ◽  
Xiangchun Li ◽  
Xining Zhang ◽  
Qinghua Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Androgen Receptor ◽  
Signaling Pathway ◽  
Gender Bias ◽  
Gender Disparity ◽  
Gene Set Enrichment Analysis ◽  
Cancer Type ◽  
Female Patients

AbstractThere is a male preponderance in gastric cancer (GC), which suggests a role of androgen and androgen receptor (AR). However, the mechanism of AR signaling in GC especially in female patients remains obscure. We sought to identify the AR signaling pathway that might be related to prognosis and examine the potential clinical utility of the AR antagonist for treatment. Deep learning and gene set enrichment analysis was used to identify potential critical factors associated with gender bias in GC (n = 1390). Gene expression profile analysis was performed to screen differentially expressed genes associated with AR expression in the Tianjin discovery set (n = 90) and TCGA validation set (n = 341). Predictors of survival were identified via lasso regression analyses and validated in the expanded Tianjin cohort (n = 373). In vitro and in vivo experiments were established to determine the drug effect. The GC gender bias was attributable to sex chromosome abnormalities and AR signaling dysregulation. The candidates for AR-related gene sets were screened, and AR combined with miR-125b was associated with poor prognosis, particularly among female patients. AR was confirmed to directly regulate miR-125b expression. AR-miR-125b signaling pathway inhibited apoptosis and promoted proliferation. AR antagonist, bicalutamide, exerted anti-tumor activities and induced apoptosis both in vitro and in vivo, using GC cell lines and female patient-derived xenograft (PDX) model. We have shed light on gender differences by revealing a hormone-regulated oncogenic signaling pathway in GC. Our preclinical studies suggest that AR is a potential therapeutic target for this deadly cancer type, especially in female patients.

scholarly journals Update on the role of pembrolizumab in patients with unresectable or metastatic colorectal cancer

2021 ◽  
Vol 14 ◽  
pp. 175628482110244
Author(s):  
Vanessa Wookey ◽  
Axel Grothey
Keyword(s):  
Colorectal Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Cancer Type ◽  
Cancer Therapies ◽  
Multiple Cancer ◽  
Multiple Treatment

Colorectal cancer (CRC) is the third most common cancer type in both men and women in the USA. Most patients with CRC are diagnosed as local or regional disease. However, the survival rate for those diagnosed with metastatic disease remains disappointing, despite multiple treatment options. Cancer therapies for patients with unresectable or metastatic CRC are increasingly being driven by particular biomarkers. The development of various immune checkpoint inhibitors has revolutionized cancer therapy over the last decade by harnessing the immune system in the treatment of cancer, and the role of immunotherapy continues to expand and evolve. Pembrolizumab is an anti-programmed cell death protein 1 immune checkpoint inhibitor and has become an essential part of the standard of care in the treatment regimens for multiple cancer types. This paper reviews the increasing evidence supporting and defining the role of pembrolizumab in the treatment of patients with unresectable or metastatic CRC.

scholarly journals LMNB2 promotes the progression of colorectal cancer by silencing p21 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Chen-Hua Dong ◽  
Tao Jiang ◽  
Hang Yin ◽  
Hu Song ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Gene Set Enrichment Analysis ◽  
Molecular Therapy ◽  
Cycle Progression ◽  
Cancer Tissues

AbstractColorectal cancer is the second common cause of death worldwide. Lamin B2 (LMNB2) is involved in chromatin remodeling and the rupture and reorganization of nuclear membrane during mitosis, which is necessary for eukaryotic cell proliferation. However, the role of LMNB2 in colorectal cancer (CRC) is poorly understood. This study explored the biological functions of LMNB2 in the progression of colorectal cancer and explored the possible molecular mechanisms. We found that LMNB2 was significantly upregulated in primary colorectal cancer tissues and cell lines, compared with paired non-cancerous tissues and normal colorectal epithelium. The high expression of LMNB2 in colorectal cancer tissues is significantly related to the clinicopathological characteristics of the patients and the shorter overall and disease-free cumulative survival. Functional analysis, including CCK8 cell proliferation test, EdU proliferation test, colony formation analysis, nude mouse xenograft, cell cycle, and apoptosis analysis showed that LMNB2 significantly promotes cell proliferation by promoting cell cycle progression in vivo and in vitro. In addition, gene set enrichment analysis, luciferase report analysis, and CHIP analysis showed that LMNB2 promotes cell proliferation by regulating the p21 promoter, whereas LMNB2 has no effect on cell apoptosis. In summary, these findings not only indicate that LMNB2 promotes the proliferation of colorectal cancer by regulating p21-mediated cell cycle progression, but also suggest the potential value of LMNB2 as a clinical prognostic marker and molecular therapy target.

Sign in / Sign up

Export Citation Format

Share Document