scholarly journals High expression of Wnt7a protein predicts a poor survival in patients with colorectal carcinoma

2020 ◽  
Author(s):  
Congcong Li ◽  
Peilin Cui ◽  
Xiaowei Dou ◽  
Hongli Li ◽  
Jiahuan Sun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Malignant Tumors ◽  
Integration Site ◽  
Normal Mucosa ◽  
Lymph Node Involvement ◽  
Colorectal Adenomas ◽  
Future Research ◽  
Colorectal Mucosa ◽  
Staining Score

Abstract Background: Colorectal cancer is one of the most common malignant tumors in China, and the number of new cases and the number of cases of deaths has increased annually. However, its pathogenesis is still unclear. Wnt7a is a member of the wingless-type MMTV integration site family, and it plays an important role in tumorigenesis and development by controlling cell proliferation and differentiation as a secreted glycoprotein. Whether Wnt7a has the properties of an oncogene or not is an important focus for future research as this target has diverse roles in different tumors.Methods: Wnt7a protein expression in normal colorectal mucosa and colorectal tumors was detected via immunohistochemistry and Western blot analysis. Univariate and multivariate analyses were used to explore the associations between Wnt7a staining score and various clinical parameters.Results: Wnt7a was strongly expressed in colorectal cancer tissues but weakly expressed in adjacent normal mucosa and colorectal adenomas. The level of Wnt7a expression was correlated with lymph node involvement (P < 0.001), Duke stage (P < 0.001), and cell differentiation (P < 0.001). Knockdown of Wnt7a inhibits proliferation of colon cancer cells and inhibits the ability of both colon cancer cell lines to migrate.Conclusions: Collectively, our results present evidence that Wnt7a is associated with an unfavorable prognosis of colorectal cancer.

scholarly journals Multiple Signatures of the JC Polyomavirus in Paired Normal and Altered Colorectal Mucosa Indicate a Link with Human Colorectal Cancer, but Not with Cancer Progression

2019 ◽  
Vol 20 (23) ◽  
pp. 5965 ◽  
Author(s):  
Elena Uleri ◽  
Claudia Piu ◽  
Maurizio Caocci ◽  
Gabriele Ibba ◽  
Francesca Sanges ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Simultaneous Detection ◽  
Normal Mucosa ◽  
T Antigen ◽  
Jc Polyomavirus ◽  
Paired Samples ◽  
Colorectal Mucosa ◽  
Viral Protein 1 ◽  
Coding Control

The JC polyomavirus (JCV) has been repeatedly but discordantly detected in healthy colonic mucosa, adenomatous polyps, and colorectal cancer (CRC), and proposed to contribute to oncogenesis. The controversies may derive from differences in JCV targets, patient’s cohorts, and methods. Studies of simultaneous detection, quantification, and characterization of JCV presence/expression in paired samples of normal/altered tissues of the same patient are lacking. Therefore, we simultaneously quantified JCV presence (DNA) and expression (mRNA and protein) of T-antigen (T-Ag), Viral Protein 1 (Vp1), and miR-J1-5p in paired normal/altered tissues of CRC or polyps, and from controls. JCV signatures were found in most samples. They increased in patients, but were higher in normal mucosa than in corresponding polyp or CRC lesions. JCV non-coding control region (NCCR) DNA rearrangements increased in CRC patients, also in normal mucosa, thus before the onset of the lesion. A new ∆98bp NCCR DNA rearrangement was detected. T-Ag levels were higher in normal mucosa than in adenoma and adenocarcinoma lesions, but decreased to levels of controls in established CRC lesions. In CRC, miR-J1-5p expression decreased with CRC progression. Vp1 expression was not detected. The data indicate a JCV link with the disease, but possible JCV contributes to oncogenesis should occur at pre-polyp stages.

scholarly journals Potential Biomarkers of Colon Adenocarcinoma Based on Weighted Gene Co-Expression Network Analysis

2021 ◽  
Author(s):  
Zhongze Cui ◽  
Shuang He ◽  
Feifei Wen ◽  
Xiaoyang Xu ◽  
Yangyang Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Colon Cancer ◽  
Network Analysis ◽  
Expression Profiles ◽  
Differential Expression Analysis ◽  
Colon Adenocarcinoma ◽  
The Cancer Genome Atlas ◽  
Future Research ◽  
Related Gene

Abstract Background: Colon adenocarcinoma (COAD) is one of the most common malignancies worldwide. Although a large number of studies have elucidated the aetiology of colorectal cancer, the exact mechanism of colorectal cancer development remains to be determined.To identify key modules and prognostic genes that may be involved in the occurrence and development of COAD, weighted gene coexpression network analysis (WGCNA) and differential expression analysis were performed on datasets GSE41657 and GSE74602 from the Gene Expression Omnibus (GEO) database to screen for prognostic differentially expressed genes. Gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) database for verification.Results: Through WGCNA and DEGs analysis, 439 genes in key functional modules were obtained, and 26 prognostic related genes were finally obtained through prognostic analysis: (1) We screened 5 genes（RPP40, DUSP18, PPRC1, MFSD11 and PDCD11） that have not been studied in COAD.（2）We obtained the most critical module in the occurrence and development of colon cancer and obtained one prognosis-related gene, NUP85, from the most critical module.The relationship between it and tumor immune microenvironment was verified.（3） A prognostic model comprising four coexpressed differential genes was constructed; TIMP1, PMM2, E2F3 and MORC2 were selected as the key prognosis-related genes.Conclusions: （1）As new biomarkers，prognostic genes RPP40, DUSP18, PPRC1, MFSD11 and PDCD11 may be potential therapeutic targets for COAD, and provide new ideas for future research on the mechanism of COAD. （2）NUP85 may be an immune-related gene which was negatively correlated with CD4+ T cell and M2 macrophagesthat plays an important role in inhibiting the occurrence and development of colorectal adenocarcinoma. （3）A Cox proportional risk model based on gene expression can be used to predict the prognosis and survival time of patients with colon cancer.

scholarly journals The Relationship between Prevention and Treatment of Colorectal Cancer and Cancerous Toxin Pathogenesis Theory Basing on Gut Microbiota

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Tianqing Sang ◽  
Wenli Qiu ◽  
Wenting Li ◽  
Hongli Zhou ◽  
Haibin Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Clinical Practice ◽  
Gut Microbiota ◽  
Malignant Tumors ◽  
Tumor Development ◽  
Technological Advances ◽  
Herbal Compound ◽  
Chinese Herbal Compound ◽  
The Relationship

Gut microbiota is a diverse consortium of bacteria, fungi, protozoa, and viruses in the gut of all mammals. Gut microbiota remains in steady state under normal conditions. Changes in the internal and external environment may cause gut Microbiota to be out of tune. Malignant tumors are one of the major diseases currently endangering human health. CRC (colorectal cancer) has a significant upward trend in morbidity and mortality in many parts of the world. Technological advances have not yet brought about a breakthrough in the efficacy of CRC. The development of colon cancer is closely related to gut microbiota imbalance. According to more than 60 years of clinical practice, Professor Zhongying Zhou first proposed the pathogenesis theory of “cancerous toxin” in the 1990s and believed that cancerous toxin was a key pathogenesis of tumor development. Under the guidance of the theory of cancerous toxin, combined with clinical practice, Professor Zhou created an effective anticancer Chinese herbal compound, Jiedu Xiaoai Prescription. This paper summarizes recent hotspots related to gut microbiota and the occurrence, development, and prevention of colon cancer at home and abroad. The relationship between gut microbiota and cancerous toxin theory is proposed, and the feasibility of further studying the biological basis of cancerous toxin pathogenesis theory from the perspective of gut microbiota is pointed out.

scholarly journals Differential Expression of Ribosomal Proteins in Human Normal and Neoplastic Colorectum

2003 ◽  
Vol 51 (5) ◽  
pp. 567-573 ◽  
Author(s):  
Hide Kasai ◽  
Daita Nadano ◽  
Eiko Hidaka ◽  
Kayoko Higuchi ◽  
Masatomo Kawakubo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ribosomal Proteins ◽  
Protein Biosynthesis ◽  
Secretory Granules ◽  
Expression Patterns ◽  
Normal Mucosa ◽  
Cellular Processes ◽  
Colorectal Mucosa ◽  
Colorectal Cancer Cells ◽  
Mucosal Cells

Ribosomal proteins are a major component of ribosomes and play critical roles in protein biosynthesis. Recently it has been shown that the ribosomal proteins also function during various cellular processes that are independent of protein biosynthesis therefore called extraribosomal functions. In this study we have, for the first time, determined the expression profile of 12 ribosomal proteins (Sa, S8, S11, S12, S18, S24, L7, L13a, L18, L28, L32, and L35a) in normal epithelia of human colorectal mucosa using immunohistochemistry (IHC) and then compared their expression patterns with those of colorectal cancer. In the normal mucosa, ribosomal proteins were largely associated with the ribosomes of mucosal epithelia, and the expression level of ribosomal proteins, except for S11 and L7 proteins, was markedly increased in associated with maturation of the mucosal cells. On the other hand, these ribosomal proteins were markedly decreased in colorectal cancer compared with the normal mucosa. By contrast, S11 and L7 ribosomal proteins were rarely associated with the ribosomes of colorectal epithlia except immature mucosal cells, whereas their expression levels were significantly enchanced in colorectal cancer cells. In addition, L7 ribosomal protien was detected in the secretory granules of the enterochromaffin cells in the colorectal mucosa and in carcinoma cells expressing chromogranin A. These results indicate that the expression of ribosomal proteins is differentially regulated not only in normal mucosa but also in carcinoma of human colorectum, and suggest an extraribosomal function of L7 ribosomal protein in neuroendocrine function.

Differential Expression of Mimecan and Thioredoxin Domain–Containing Protein 5 in Colorectal Adenoma and Cancer: A Proteomic Study

2007 ◽  
Vol 232 (9) ◽  
pp. 1152-1159 ◽  
Author(s):  
Yinghong Wang ◽  
Yu Ma ◽  
Bingjian Lü ◽  
Enping Xu ◽  
Qiong Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Adenoma ◽  
Normal Mucosa ◽  
Colorectal Adenomas ◽  
Differentially Expressed ◽  
Cancer Tissue ◽  
Differentially Expressed Proteins ◽  
Two Dimensional Gel Electrophoresis ◽  
Proteomic Study ◽  
Cancer Tissues

Adenoma is the major precursor lesion of colorectal cancer, one of the most common cancers worldwide. The elucidation of the molecular mechanism underlying adenoma is essential for early detection, prevention, and intervention of colorectal cancer. Using a combination of two-dimensional gel electrophoresis and mass spectrometry, we identified 27 differentially expressed proteins in adenoma, compared with matched normal mucosa and cancer tissue. Seventeen proteins were upregulated and six downregulated in adenoma when compared with the same proteins in individual-matched normal mucosa. Four were downregulated, but none upregulated in adenoma when compared with the same proteins in matched cancer tissue. Two novel proteins, mimecan and thioredoxin domain–containing protein 5 (TXNDC5), were further validated by Western blot in 8 colorectal adenomas and 19 cancers that were matched with normal mucosa. All adenoma and cancer tissues did not express mimecan, but all normal mucosa did ( P < 0.01). In contrast, TXNDC5 was significantly upregulated in colorectal adenoma and cancer tissues as compared with that in normal mucosa ( P < 0.05). This study clearly demonstrated that absence of mimecan and upregulation of TXNDC5 are involved in the early development of colorectal cancer. Thus, the differentially expressed proteins might serve as potential biomarkers for colorectal cancer detection and intervention.

miR-223 Promotes Proliferation of Colon Cancer Cells by Down-Regulating Bcl-2-Like Protein 11 (BIM) Expression

2019 ◽  
Vol 9 (10) ◽  
pp. 1424-1428
Author(s):  
Zhouyang Cheng ◽  
Yang Cao ◽  
Qingfeng Ni ◽  
Jun Qin
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Malignant Tumors ◽  
Luciferase Reporter ◽  
Colon Cancer Cells ◽  
Luciferase Reporter Gene ◽  
Real Time Quantitative Pcr ◽  
Cancer Tissues

Colorectal cancer is one of malignant tumors. microRNA plays an important role in various diseases. In this study, we evaluated miR-223's effect on the proliferation of colon cancer cells. Protein and RNA expression levels in patients with clinical colorectal cancer were determined by western blot and real-time quantitative PCR respectively. In addition, the mechanism of miR-223 action was explored by combining transfection methods in cell lines. Colon cancer tissues showed significantly elevated miR-223 expression compared with adjacent tissues. Meanwhile, FOXO3a and BIM protein levels were significantly lower in cancer tissues compared to adjacent tissues. In colon cancer cell lines, knockdown of miR-223 increased cell proliferation and decreased BIM expression. The luciferase reporter gene showed that miR-223 down-regulates BIM expression through targeting FOXO3a. In colon cancer cells, miR-223 can down-regulate BIM expression through FOXO3a, thereby promoting the proliferation of colon cancer cells, indicating that targeting miR-223-regulated FOXO3a pathway might lead to the development of a number of drugs, and it is feasible to have a purpose to regulate the behavior of malignant cells.

Factors contributing to the black/white colorectal cancer survival disparity in nonelderly patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3587-3587
Author(s):  
Helmneh M. Sineshaw ◽  
Kimmie Ng ◽  
W. Dana Flanders ◽  
Otis W. Brawley ◽  
Ahmedin Jemal
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Survival ◽  
Tumor Location ◽  
National Cancer Data Base ◽  
Future Research ◽  
Treatment Matching ◽  
Entire Cohort ◽  
Cancer Data ◽  
Survival Difference

3587 Background: Previous studies reported that black/white survival disparities among elderly colorectal cancer (CRC) patients largely reflect differences in tumor presentation rather than differences in treatment. We sought to determine the contribution of differences in tumor presentation and receipt of treatment to the black/white survival disparity among nonelderly CRC patients. Methods: We selected non-Hispanic black (black) and Non-Hispanic white (white) patients aged 18-64 years, and diagnosed between 2004-2012 with single or first primary invasive stage I-IV CRC in the National Cancer Data Base. Blacks were sequentially matched with three white comparison cohorts, using propensity score and greedy matching algorithm, by demographics (age, sex, diagnosis year, region), tumor presentation (stage, grade, margin, tumor location, node status, comorbidity score), and treatment (surgery, chemotherapy, radiotherapy, metastatectomy) characteristics. We used Kaplan-Meier method to estimate 5-year survival for blacks compared with whites in the entire cohort and in the three sequentially matched cohorts. Results: In the entire cohort, 5-year survival was 9.2% lower in nonelderly blacks than whites (57.3% vs 66.5%). The survival difference remained unchanged after demographic matching, but it decreased to 3.3% (5.9% absolute and 64% relative reductions) after tumor presentation matching, and to 2.6% (0.7% absolute and 7.6% relative reductions) after treatment matching. By anatomic subsite, treatment matching reduced the black/white 5-year survival difference by 26% (3%/11.5%) for rectal cancer, only by 5.6% (0.5%/9%) for left colon cancer, and no change for right colon cancer. Conclusions: Differences in tumor presentation characteristics explained about two-thirds of the black/white survival disparity in nonelderly CRC patients, while treatment explained less than ten percent of the disparity. Future research should explore the biological mechanisms underlying these observed differences in tumor presentation and implications for treatment.

scholarly journals Overexpression of GRK3, Promoting Tumor Proliferation, Is Predictive of Poor Prognosis in Colon Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Tao Jiang ◽  
Chun Yang ◽  
Liyuan Ma ◽  
Zehua Wu ◽  
Ling Ye ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Xenograft Model ◽  
Growth Index ◽  
Prognostic Indicator ◽  
Normal Mucosa ◽  
Lymph Node Involvement ◽  
Index Reduction ◽  
Primary Colon Cancer ◽  
Primary Colon ◽  
Node Involvement

Deregulation of G protein-coupled receptor kinase 3 (GRK3), which belongs to a subfamily of kinases called GRKs, acts as a promoter mechanism in some cancer types. Our study found that GRK3 was significantly overexpressed in 162 pairs of colon cancer tissues than in the matched noncancerous mucosa (P<0.01). Based on immunohistochemistry staining of TMAs, GRK3 was dramatically stained positive in primary colon cancer (130/180, 72.22%), whereas it was detected minimally or negative in paired normal mucosa specimens (50/180, 27.78%). Overexpression of GRK3 was closely correlated with AJCC stage (P=0.001), depth of tumor invasion (P<0.001), lymph node involvement (P=0.004), distant metastasis (P=0.016), and histologic differentiation (P=0.004). Overexpression of GRK3 is an independent prognostic indicator that correlates with poor survival in colon cancer patients. Consistent with this, downregulation of GRK3 exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate, and impaired colon tumorigenicity in a xenograft model. Hence, a specific overexpression of GRK3 was observed in colon cancer, GRK3 potentially contributing to progression by mediating cancer cell proliferation and functions as a poor prognostic indicator in colon cancer and potentially represent a novel therapeutic target for the disease.

Clinical and molecular characteristics of younger versus older patients with colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 630-630
Author(s):  
Pritish Iyer ◽  
Kit Wong ◽  
Christopher Hanyoung Lieu ◽  
Jason Henry ◽  
Sarah Lindsey Davis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Older Patients ◽  
Molecular Mechanisms ◽  
Young Patients ◽  
Future Research ◽  
Molecular Characteristics ◽  
Young Cohort ◽  
Braf Mutations ◽  
Younger Patients

630 Background: Although overall incidence of colorectal cancer is declining, the incidence for young patients (age < 50) with colon cancer is increasing. Reasons for this rise are unclear. Understanding clinical and molecular differences between younger and older cohorts can help guide both patient education strategies and future research into the mechanisms of this phenomenon. Methods: A retrospective analysis of patients diagnosed with colon cancer between 2008 and 2015 who underwent molecular tumor profiling via next-gen sequencing of 26 commonly mutated genes at the University of Colorado. Data collected by chart review includes demographic, pathologic, treatment course, and outcomes. Age group cutoffs for data analysis were set at < 50, 50-65, and > 65 based on screening guidelines and average age of diagnosis Results: We evaluated a total of 242 patients, stage I (n = 1), stage II (n = 65), stage III (n = 68), stage IV (n = 105). Mean age was 59.5 (range 27 to 89). A higher percentage of younger patients were non-smokers (77% of youngest cohort vs 46% of oldest cohort, p < 0.001) and had a non-significant trend towards male gender (youngest cohort 63.8% male, oldest cohort 43.4% male, p = 0.065). Younger patients had similar body mass index (BMI) compared to older patients (BMI 27 vs 25.7, p = 0.35). Younger patients had higher rates of rectal cancer (42% vs 21%, p = 0.01) and lower rates of proximal/right sided colon cancer (20% vs 46.5%, p = 0.014). Younger patients also had lower rates of MSI-H tumors (8% vs 14%, p = 0.01). Finally, younger patients had significantly lower rates of APC (43.1% vs 69.3%, p = 0.009) and BRAF (3.5% vs 19.7%, p = 0.004) mutations. Conclusions: Younger patients ( < 50 years old) with colorectal cancer had lower rates of tobacco use and no difference in obesity rates compared to older patients. In addition, although APC and BRAF mutations were lower in younger patients, there were no mutations that were more prevalent in the young cohort. Therefore, further research into lifestyle factors (specific diet/exercise patterns) or alternative molecular mechanisms are needed.

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