The Construction of a Multi-Gene Risk Model for Colon Cancer Prognosis and Drug Treatments Prediction.

In clinical practice, colon cancer is a prevalent malignant tumor of the digestive system, characterized by a complex and progressive process involving multiple genes and molecular pathways. Historically, research efforts have primarily focused on investigating individual genes; however, our current study aims to explore the collective impact of multiple genes on colon cancer and to identify potential therapeutic targets associated with these genes. For this research, we acquired the gene expression profiles and RNA sequencing data of colon cancer from TCGA. Subsequently, we conducted differential gene expression analysis using R, followed by GO and KEGG pathway enrichment analyses. To construct a protein-protein interaction (PPI) network, we selected survival-related genes using the log-rank test and single-factor Cox regression analysis. Additionally, we performed LASSO regression analysis, immune infiltration analysis, mutation analysis, and cMAP analysis, as well as an investigation into ferroptosis. Our differential expression and survival analyses identified 47 hub genes, and subsequent LASSO regression analysis refined the focus to 23 key genes. These genes are closely linked to cancer metastasis, proliferation, apoptosis, cell cycle regulation, signal transduction, cancer microenvironment, immunotherapy, and neurodevelopment. Overall, the hub genes discovered in our study are pivotal in colon cancer and are anticipated to serve as important biological markers for the diagnosis and treatment of the disease.

Epigenetic Alteration in Colorectal Cancer: Potential Diagnostic and Prognostic Implications.

Colorectal cancer (CRC), a prevalent malignant tumor of the digestive system, ranks as the third and second in global incidence and mortality, respectively, in 2020, with 1.93 million new cases (≈10% of all cancers). There are 940,000 deaths (≈9.4% of all cancers), and the incidence of CRC in younger patients (under 50 years of age) has become a new trend. The pathogenesis of CRC is primarily attributed to a series of genetic and epigenetic abnormalities within normal colonic epithelial cells, coupled with the reshaping of the tumor microenvironment in the surrounding stroma. This process leads to the transformation of colorectal adenomas into invasive adenocarcinomas. Although genetic changes are known to be the primary driving force in the occurrence and progression of CRC, recent research indicates that epigenetic regulation serves as a crucial molecular marker in cancer, playing a significant role in the pathological and physiological control of interactions between genetics and the environment. This review discusses the current global epidemiology of CRC, its risk factors, and preventive treatment strategies. The current study explores the latest advancements in the epigenetic regulation of CRC, including DNA methylation, histone modifications, and non-coding RNAs (ncRNAs). These developments hold potential as screening tools, prognostic biomarkers, and therapeutic targets for CRC.

PEX26 Functions as a Metastasis Suppressor in Colorectal Cancer.

BACKGROUND/AIMS: Aberrant Peroxisomal Biogenesis Factor 26 (PEX26) occurs in multiple cell process. However, the role of PEX26 in colorectal cancer (CRC) development remains unknown. We aimed to study PEX26 expression, regulation, and function in CRC cells. METHODS: Using the bioinformatic analysis, real-time quantitative PCR, and immunohistochemistry staining, we detected the expression of PEX26 in CRC and normal tissues. We performed functional experiments in vitro to elucidate the effect of PEX26 on CRC cells. We analyzed the RNA-seq data to reveal the downstream regulating network of PEX26. RESULTS: PEX26 is significantly down-regulated in CRC and its low expression correlates with the poor overall survival of CRC patients. We further demonstrated that PEX26 over-expression inhibits the ability of CRC cell migration, invasion, and epithelial-mesenchymal transition (EMT), while PEX26 knockdown promotes the malignant phenotypes of migration, invasion, and EMT via activating the Wnt pathway. CONCLUSION: Overall, our results showed that the loss of PEX26 contributes to the malignant phenotype of CRC. PEX26 may serve as a novel metastasis repressor for CRC.

Loss of Tumor Suppressor C9orf9 Promotes Metastasis in Colorectal Cancer.

The whole genome sequencing of tumor samples identifies thousands of somatic mutations. However, the function of these genes or mutations in regulating cancer progression remains unclear. We previously performed exome sequencing in patients with colorectal cancer, and identified one splicing mutation in C9orf9. The subsequent target sequencing of C9orf9 gene based on a validation cohort of 50 samples also found two function mutations, indicating that the loss of wild-type C9orf9 may participate in the tumorigenesis of colorectal cancer. In this research, we aimed to further confirm the function of C9orf9 in the CRC phenotype. Our Q-PCR analysis of the tumor and matched normal samples found that C9orf9 was downregulated in the CRC samples. Function assays revealed that C9orf9 exerts its tumor suppressor role mainly on cancer cell migration and invasion, and its loss was essential for certain tumor-microenvironment signals to induce EMT and metastasis in vivo. RNA-sequencing showed that stable-expressing C9orf9 can inhibit the expression of several metastasis-related genes and pathways, including vascular endothelial growth factor A (VEGFA), one of the essential endothelial cell mitogens which plays a critical role in normal physiological and tumor angiogenesis. Overall, our results showed that the loss of C9orf9 contributes to the malignant phenotype of CRC. C9orf9 may serve as a novel metastasis repressor for CRC.

Efficacy of non-pharmacological interventions in females with overactive bladder: A systematic review and network meta-analysis.

AIMS AND OBJECTIVES: To compare and rank the effectiveness of non-pharmacological interventions for symptoms of Overactive Bladder (OAB) in network meta-analysis. BACKGROUND: Overactive Bladder affects many patients, which often generates bothersome symptoms and debilitates the quality of life. Non-pharmacological therapies have been widely used in OAB. However, due to insufficient evidence, it remains unclear which strategies are most suitable for OAB. METHODS: We integrated randomised controlled trials (RCTs), which were searched up to 1 January 2021, from 8 databases (PubMed, Embase, Cochrane library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc). Studies that met the eligible criteria were assessed the risk of bias. Then, network meta-analyses were conducted by STATA, R, and OpenBUGS. The review followed PRISMA statement. RESULTS: A total of 24 studies comprising 2347 patients with OAB were included in this review, most of which were low to moderate risk of bias. The results of network meta-analysis implied that electric stimulation (ES) was the most effective intervention to reduce voided frequency and nocturia frequency of OAB. CONCLUSIONS: Electric stimulation ranked the best in the management of OAB, and future studies should pay more attention to ES.

MicroRNAs Are Key Molecules Involved in the Gene Regulation Network of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common types of cancer and one of the leading causes of mortality worldwide. MicroRNAs (miRNAs) play central roles in normal cell maintenance, development, and other physiological processes. Growing evidence has illustrated that dysregulated miRNAs can participate in the initiation, progression, metastasis, and therapeutic resistance that confer miRNAs to serve as clinical biomarkers and therapeutic targets for CRC. Through binding to the 3'-untranslated region (3'-UTR) of target genes, miRNAs can lead to target mRNA degradation or inhibition at a post-transcriptional level. During the last decade, studies have found numerous miRNAs and their potential targets, but the complex network of miRNA/Targets in CRC remains unclear. In this review, we sought to summarize the complicated roles of the miRNA-target regulation network (Wnt, TGF-ß, PI3K-AKT, MAPK, and EMT related pathways) in CRC with up-to-date, high-quality published data. In particular, we aimed to discuss the downstream miRNAs of specific pathways. We hope these data can be a potent supplement for the canonical miRNA-target regulation network.

Exploring Immune-Related Prognostic Signatures in the Tumor Microenvironment of Colon Cancer.

Background: Colon cancer is a common malignant tumor with poor prognosis. The aim of this study is to explore the immune-related prognostic signatures and the tumor immune microenvironment of colon cancer. Methods: The mRNA expression data of TCGA-COAD from the UCSC Xena platform and the list of immune-related genes (IRGs) from the ImmPort database were used to identify immune-related differentially expressed genes (DEGs). Then, we constructed an immune-related risk score prognostic model and validated its predictive performance in the test dataset, the whole dataset, and two independent GEO datasets. In addition, we explored the differences in tumor-infiltrating immune cell types, tumor mutation burden (TMB), microsatellite status, and expression levels of immune checkpoints and their ligands between the high-risk and low-risk score groups. Moreover, the potential value of the identified immune-related signature with respect to immunotherapy was investigated based on an immunotherapeutic cohort (Imvigor210) treated with an anti-PD-L1 agent. Results: Seven immune-related DEGs were identified as prognostic signatures. The areas under the curves (AUCs) of the constructed risk score model for overall survival (OS) were calculated (training dataset: 0.780 at 3 years, 0.801 at 4 years, and 0.766 at 5 years; test dataset: 0.642 at 3 years, 0.647 at 4 years, and 0.629 at 5 years; and the whole dataset: 0.642 at 3 years, 0.647 at 4 years, and 0.629 at 5 years). In the high-risk score group of the whole dataset, patients had worse OS, higher TMN stages, advanced pathological stages, and a higher TP53 mutation rate (p < 0.05). In addition, a high level of resting NK cells or M0 macrophages, and high TMB were significantly related to poor OS (p < 0.05). Also, we observed that high-risk score patients had a high expression level of PD-L1, PD-1, and CTLA-4 (p < 0.05). The patients with high-risk scores demonstrated worse prognosis than those with low-risk scores in multiple datasets (GSE39582: p = 0.0023; GSE17536: p = 0.0008; immunotherapeutic cohort without platinum treatment: p = 0.0014; immunotherapeutic cohort with platinum treatment: p = 0.0027). Conclusion: We developed a robust immune-related prognostic signature that performed great in multiple cohorts and explored the characteristics of the tumor immune microenvironment of colon cancer patients, which may give suggestions for the prognosis and immunotherapy in the future.

ZNF3 regulates proliferation, migration and invasion through MMP1 and TWIST in colorectal cancer.

Colorectal cancer (CRC) is a malignant tumor with a high incidence and mortality worldwide. Currently, the underlying molecular mechanisms of CRC are still unclear. Zinc finger protein 3 (ZNF3) is a zinc-finger transcription factor that has been reported as a candidate for breast cancer prognosis, suggesting its involvement in the regulation of tumorigenesis. However, the association between ZNF3 and CRC remains unknown. To investigate the role of ZNF3 in CRC, we first analyze the correlation between ZNF3 expression and CRC, and the results demonstrate that ZNF3 is highly expressed in CRC tissue and cells, which is associated with the age of CRC patients. In vitro studies show that ZNF3 overexpression promotes CRC cell migration. Compared to control cells, knockdown of ZNF3 markedly suppresses CRC cell proliferation, migration and invasion and promotes G0/G1 phase cell cycle arrest. The expressions of the EMT-related markers TWIST and MMP1 are significantly decreased when ZNF3 is silenced. Additionally, overexpression of MMP1 and TWIST exacerbates CRC cell proliferation, accelerates the S phase cell cycle in ZNF3-knockdown SW480 cells, and increases cell migration and invasion through Transwell chambers. These data suggest that ZNF3 is involved in cellular proliferation, migration and invasion by regulating MMP1 and TWIST in CRC cells.

Construction of a novel methylation-related prognostic model for colorectal cancer based on microsatellite status.

The present study aimed to construct a novel methylation-related prognostic model based on microsatellite status that may enhance the prognosis of colorectal cancer (CRC) from methylation and microsatellite status perspective. DNA methylation and mRNA expression data with clinical information were downloaded from The Cancer Genome Atlas (TCGA) data set. The samples were divided into microsatellite stability and microsatellite instability group, and CIBERSORT was used to assess the immune cell infiltration characteristics. After identifying the differentially methylated genes and differentially expression genes using R packages, the methylation-driven genes were further identified. Prognostic genes that were used to establish the methylation-related risk score model were generated by the univariate and multivariate Cox regression model. Finally, we established and evaluated the methylation-related prognostic model for CRC patients. A total of 69 MDGs were obtained and three of these genes (MIOX, TH, DKFZP434K028) were selected to construct the prognostic model. Patients in the low-risk score group had a conspicuously better overall survival than those in the high-risk score group (p < .0001). The area under the receiver operating characteristic curve for this model was 0.689 at 3 years, 0.674 at 4 years, and 0.658 at 5 years. The Wilcoxon test showed that higher risk score was associated with higher T stage (p = .01), N stages (p = .0028), metastasis (p = .013), and advanced pathological stage (p = .0013). However, the more instability of microsatellite status, the lower risk score of CRC patients (p = .0048). Our constructed methylation-related prognostic model based on microsatellite status presents potential significance in assessing recurrence risk stratification, tumor staging, and immunotherapy for CRC patients.

Decreased level of miR-1301 promotes colorectal cancer progression via activation of STAT3 pathway.

The molecular pathogenesis of colorectal cancer (CRC) has been widely investigated in recent years. Accumulating evidence has indicated that microRNA (miRNA) dysregulation participates in the processes of driving CRC initiation and progression. Aberrant expression of miR-1301 has been found in various tumor types. However, its role in CRC remains to be elucidated. In the present study, we identified miR-1301 was enriched in normal colorectal tissues and significantly down-regulated in CRC. Decreased level of miR-1301 strongly correlated with aggressive pathological characteristics, including advanced stage and metastasis. Bioinformatics and dual luciferase assay demonstrated that STAT3 is a direct target of miR-1301. Gain and loss-of-function assays showed that miR-1301 had no effect on cell proliferation. Overexpression of miR-1301 suppressed cell migration and invasion capacity of pSTAT3-positive LoVo cells, but not pSTAT3-negative SW480 cells, while inhibition of miR-1301 consistently promoted cell migration and invasion in both cell lines. Additionally, miR-1301 inhibition restored the suppressed migration and invasion of STAT3-knockdown LoVo cells. MiR-1301 functioned as a tumor suppressor to modulate the IL6/STAT3 signaling pathway. In summary, this study highlights the significant role of miR-1301/STAT3 axis in CRC metastasis.

MiR-581/SMAD7 Axis Contributes to Colorectal Cancer Metastasis: A Bioinformatic and Experimental Validation-Based Study.

Metastasis is a well-known poor prognostic factor and primary cause of mortality in patients with colorectal cancer (CRC). Recently, with the progress of high through-put sequencing, aberrantly expressed non-coding RNAs (ncRNAs) were found to participate in the initiation and development of cancer. However, the mechanisms of ncRNA-mediated regulation of metastasis in CRC remain largely unknown. In this study, we systematically analyzed the expression network of microRNAs (miRNAs) and genes in CRC metastasis using bioinformatics, and discovered that the miR-581/SMAD7 axis could be a potential factor that drives CRC metastasis. A dual luciferase report assay and protein analysis confirmed the binding relationship between miR-581 and SMAD7. Further functional assays revealed that miR-581 inhibition could suppress cell proliferation and induce apoptosis in SW480 cells. Up-regulation or down-regulation of miR-581 could both affect cell invasion capacity and modulate epithelial to mesenchymal transition (EMT) via a SMAD7/TGFß signaling pathway. In conclusion, our findings elucidated that miR-581/SMAD7 could be essential for CRC metastasis, and may serve as a potential therapeutic target for CRC patients.

MiR-496 promotes migration and epithelial-mesenchymal transition by targeting RASSF6 in colorectal cancer.

Aberrant loss of tumor-suppressor genes plays a crucial role in tumorigenesis and development of colorectal cancer (CRC). Extensive studies have reported tha hypermethylation of Ras association domain family member 6 (RASSF6) is common in various solid tumors. Another important mode of epigenetic regulation, microRNA (miRNA) regulation of RASSF6, is far from clear. The aim of the present work was to screen out novel miRNA regulating RASSF6, and to explore its underlying mechanism in CRC. With the use of bioinformatics, clinical sample data, and luciferase binding assay, we determined that microRNA-496 (miR-496) could be a novel oncomiR that directly binds to RASSF6. Next, a series of miR-496 mimics or inhibitor, or RASSF6 small interfering RNA (siRNA) introduced into CRC cells were applied to examine the effect of miR-496 on CRC cell viability, migration, and epithelial-mesenchymal transition (EMT). The results demonstrated that miR-496/RASSF6 could promote cell migration and EMT via Wnt signaling activation, but had no effect on cell viability. Our results confirmed that the miR-496/RASSF6 axis is involved in Wnt pathway-mediated tumor metastasis, highlighting its potential as a therapeutic target for CRC.

Construction and Validation of an Immune-Related Prognostic Model Based on TP53 Status in Colorectal Cancer.

Growing evidence has indicated that prognostic biomarkers have a pivotal role in tumor and immunity biological processes. TP53 mutation can cause a range of changes in immune response, progression, and prognosis of colorectal cancer (CRC). Thus, we aim to build an immunoscore prognostic model that may enhance the prognosis of CRC from an immunological perspective. We estimated the proportion of immune cells in the GSE39582 public dataset using the CIBERSORT (Cell type identification by estimating relative subset of known RNA transcripts) algorithm. Prognostic genes that were used to establish the immunoscore model were generated by the LASSO (Least absolute shrinkage and selection operator) Cox regression model. We established and validated the immunoscore model in GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) cohorts, respectively; significant differences of overall survival analysis were found between the low and high immunoscore groups or TP53 subgroups. In the multivariable Cox analysis, we observed that the immunoscore was an independent prognostic factor both in the GEO cohort (HR (Hazard ratio) 1.76, 95% CI (confidence intervals): 1.26-2.46) and the TCGA cohort (HR 1.95, 95% CI: 1.20-3.18). Furthermore, we established a nomogram for clinical application, and the results suggest that the nomogram is a better predictive model for prognosis than immunoscore or TNM staging.

The Akt/FoxO/p27Kip1 axis contributes to the anti-proliferation of pentoxifylline in hypertrophic scars.

Hypertrophic scars (HS) are characterized by the excessive production and deposition of extracellular matrix (ECM) proteins. Pentoxifylline (PTX), a xanthine derived antioxidant, inhibits the proliferation, inflammation and ECM accumulation of HS. In this study, we aimed to explore the effect of PTX on HS and further clarify the mechanism of PTX-induced anti-proliferation. We found that PTX could significantly attenuate proliferation of HS fibroblasts and fibrosis in an animal HS model. PTX inhibited the proliferation of HSFs in a dose- and time-dependent manner, and this growth inhibition was mainly mediated by cell cycle arrest. Transcriptome sequencing showed that PTX affects HS formation through the PI3K/Akt/FoxO1 signalling pathway to activate p27Kip1 . PTX down-regulated p-Akt and up-regulated p-FoxO1 in TGF-ß1 stimulated fibroblasts at the protein level, and simultaneously, the expression of p27Kip1 was activated. In a mouse model of HS, PTX treatment resulted in the ordering of collagen fibres. The results revealed that PTX regulates TGFß1-induced fibroblast activation and inhibits excessive scar formation. Therefore, PTX is a promising agent for the treatment of HS formation.

MicroRNA-3191 promotes migration and invasion by downregulating TGFBR2 in colorectal cancer.

Mutations in transforming growth factor beta receptor II (TGFBR2) are detected in up to 30% of overall colorectal cancer (CRC). Dysregulation of some microRNAs participated in the CRC pathogenesis. In this study, we used the gene ontology analyses, the Kyoto Encyclopedia of Genes and Genomes pathway analyses and gene set enrichment analysis to indicate that miR-3191 was involved in the regulation of transforming growth factor beta (TGF-BETA) signal pathway in CRC. These bioinformatics results were supported by data obtained from CRC samples and experiments in vitro. The luciferase reporter assay was used to confirm that miR-3191 modulates TGF-BETA signal pathway by targeting TGFBR2. By transwell migration and invasion assays, we showed that miR-3191 promoted CRC cell migration and invasion by downregulating TGFBR2. And it may serve as a novel therapeutic strategy for treating CRC patients.

Alteration of the tumor suppressor SARDH in sporadic colorectal cancer: A functional and transcriptome profiling-based study.

Sporadic colorectal cancer (sCRC) is one of the leading causes of cancer death worldwide. As a highly heterogeneous complex disease, the currently reported classical genetic markers for sCRC, including APC, KRAS, BRAF, and TP53 gene mutations and epigenetic alterations, can explain only some sCRC patients. Here, we first reported a deleterious c.551C>T mutation in SARDH in sCRC. SARDH was identified as a novel tumor suppressor gene and was abnormally decreased in sCRC at both the transcriptional and the translational level. SARDH mRNA levels were also down-regulated in oesophageal cancer, lung cancer, liver cancer, and pancreatic cancer in the TCGA database. SARDH overexpression inhibited the proliferation, migration, and invasion of CRC cell lines, whereas its depletion improved these processes. SARDH overexpression was down-regulated in multiple pathways, especially in the chemokine pathway. The SARDH transcript level was positively correlated with the methylation states of CXCL1 and CCL20. Therefore, we concluded that SARDH depletion is involved in the development of sCRC.

Alteration of tumor suppressor BMP5 in sporadic colorectal cancer: a genomic and transcriptomic profiling based study.

BACKGROUND: Although the genetic spectrum of human colorectal cancer (CRC) is mainly characterized by APC, KRAS and TP53 mutations, driver genes in tumor initiation have not been conclusively demonstrated. In this study, we aimed to identify novel markers for CRC. METHODS: We performed exome analysis of sporadic colorectal cancer (sCRC) coding regions to screen loss of function (LoF) mutation genes, and carried out systems-level approaches to confirm top rank gene in this study. RESULTS: We identified loss of BMP5 is an early event in CRC. Deep sequencing identified BMP5 was mutated in 7.7% (8/104) of sCRC samples, with 37.5% truncating mutation frequency. Notably, BMP5 negative expression and its prognostic value is uniquely significant in sCRC but not in other tumor types. Furthermore, BMP5 expression was positively correlated with E-cadherin in CRC patients and its dysregulation play a vital role in epithelial-mesenchymal transition (EMT), thus triggering tumor initiation and development. RNA sequencing identified, independent of BMP/Smads pathway, BMP5 signaled though Jak-Stat pathways to inhibit the activation of oncogene EPSTI1. CONCLUSIONS: Our result support a novel concept that the importance of BMP5 in sCRC. The tumor suppressor role of BMP5 highlights its crucial role in CRC initiation and development.

MiR-92a promotes tumorigenesis of colorectal cancer, a transcriptomic and functional based study.

Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Accumulation of varieties of epigenetic changes, including miRNA regulation, is one of the fundamental processes driving CRC initiation and progression. Mir-92a has been reported in several studies as an oncogene, and particularly in colorectal cancer, it has become a useful biomarker for early detection of CRC in both serum or stool. The Cancer Genome Atlas (TCGA) is a powerful database to analyze cancer-related genes and their correlation with patients' pathological information. However, miR-92a expression and its regulating target genes has yet to be investigated in TCGA system. In this study, we found miR-92a expression is associated with CRC pathological process. Notably, high expression of miR-92a mainly occurs in microsatellite-stable (MSS) cases. Further experiments showed exogenous introduction of miR-92a into LoVo and SW480 cells could enhance cell proliferation, migration, and invasion, whereas inhibition of miR-92a showed the opposite effects. A system analysis based on binding capacity and expression correlation analysis confirmed DKK3 and KLF4 are the top target genes of miR-92a, and novel target SMAD7 highlights the role of miR-92a in BMPs/SMAD pathway. In conclusion, miR-92a acts as an oncomir and directly targets Wnt/ß-catenin, PTEN/Akt/FoxO, and BMP/Smads related genes, thus participates in CRC progression.

MiR-32 promotes tumorigenesis of colorectal cancer by targeting BMP5.

MiRNA regulation is a crucial way of epigenetic changes. Mir-32 has been reported in several studies as an oncogene, however, its role and target in colorectal cancer (CRC) remains unclear. In this study, we aimed to explore the role of miR-32 in CRC using bioinformatic analysis and functional assays. We collected 28 pairs of CRC tumor tissues and adjacent normal tissues and confirmed miR-32 was significantly upregulated in CRC. Expression and clinical data from The Cancer Genome Atlas (TCGA) identified miR-32 expression is associated with CRC lymphatic invasion, metastasis, and correlates with patients' poor survival. Functional studies demonstrated that overexpression of miR-32 in LoVo cells promoted cell proliferation and migration, whereas inhibition of miR-32 in HCT 116 cells showed the opposite results. Using bioinformatics, we identified Bone morphogenetic protein 5 (BMP5) is a direct target of miR-32, and loss of tumor suppressor BMP5 may partially due to the miR-32 dysregulation. The inverse correlation between miR-32 and BMP5 was observed in CRC, especially in advanced tumor patients. Moreover, cotransfection of miR-32 mimics and BMP5 recombinant vector in LoVo cells demonstrated that BMP5 could reverse the oncomir effect of miR-32. Taken together, our results suggested a significant role of miR-32/BMP5 axis in CRC tumorigenesis.

High Vimentin Expression Predicts a Poor Prognosis and Progression in Colorectal Cancer: A Study with Meta-Analysis and TCGA Database.

The aim of this study was to evaluate the role of vimentin expression in the prognosis and progression of CRC. Meta-analysis was conducted to investigate the correlations between vimentin and prognosis and clinicopathological features in CRC. Literatures were searched by PubMed, Embase, ClinicalKey, CNKI, VIP, and WanFang databases. The Cancer Genome Atlas (TCGA) database was used to assess the association of vimentin expression with survival rate in CRC. Eleven reports with 1969 cases were included in the meta-analysis. The results showed that positive vimentin expression predicted a poor overall survival (OS) in the univariate analysis (HR: 2.087, 95%CI: 1.660-2.625) and multivariate analysis (HR: 1.633, 95%CI: 1.223-2.181). Vimentin overexpression also conferred worse disease-free survival (DFS) in the univariate analysis (HR: 2.069, 95%CI: 1.024-4.179) and multivariate analysis (HR: 2.802, 95%CI: 1.421-5.527). Moreover, upregulated vimentin is related to lymph node metastasis (OR: 2.288, 95%CI: 1.159-4.517), TNM stages (OR: 1.957, 95%CI: 1.333-2.873), and N stage (OR: 2.316, 95%CI: 1.482-3.620). Analysis of TCGA database indicated that elevated vimentin predicated a shorter OS (p=0.033). Our findings reveal that upregulated vimentin contributes to the progression and poor prognosis of CRC. Vimentin may be a prognostic biomarker and therapeutic target in patients with CRC.