scholarly journals Impact of FGFR4 Gene Polymorphism on the Progression of Colorectal Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 978
Author(s):  
Bei-Hao Shiu ◽  
Ming-Hong Hsieh ◽  
Wen-Chien Ting ◽  
Ming-Chih Chou ◽  
Lun-Ching Chang ◽  
...  

Colorectal cancer (CRC) is a multifactorial malignancy, and its high incidence and mortality rate remain a global public health burden. Fibroblast growth factor receptor 4 (FGFR4) is a receptor tyrosine kinase that has been shown to play a key role in cancer development and prognosis via the activation of its downstream oncogenic signaling pathways. The present study aimed to explore the impact of FGFR4 gene polymorphisms on the risk and progression of CRC. Three FGFR4 single-nucleotide polymorphisms (SNPs), including rs1966265, rs351855, and rs7708357, were evaluated in 413 CRC cases and 413 gender- and age-matched cancer-free controls. We did not observe any significant association of three individual SNPs with the risk of CRC between the case and control group. However, while assessing the clinicopathological parameters, patients of rectal cancer possessing at least one minor allele of rs1966265 (AG and GG; AOR, 0.236; p = 0.046) or rs351855 (GA and AA; AOR, 0.191; p = 0.022) were found to develop less metastasis as compared to those who are homozygous for the major allele. Further analyses using the datasets from the Genotype-Tissue Expression (GTEx) Portal and The Cancer Genome Atlas (TCGA) revealed that rs351855 regulated FGFR4 expression in many human tissues, and increased FGFR4 levels were associated with the occurrence, advanced stage, and distal metastasis of colon adenocarcinoma. These data suggest that the amino acid change in combination with altered expression levels of FGFR4 due to genetic polymorphisms may affect CRC progression.

2021 ◽  
Vol 11 (6) ◽  
pp. 468
Author(s):  
Shih-Chi Su ◽  
Chiao-Wen Lin ◽  
Po-Chung Ju ◽  
Lun-Ching Chang ◽  
Chun-Yi Chuang ◽  
...  

Oral squamous cell carcinoma (OSCC) is a multifactorial malignancy, and its high incidence and mortality rate remain a global public health burden. Polymorphisms in the long intergenic noncoding RNA 673 (LINC00673) have been currently connected to the predisposition to various cancer types. The present study attempted to explore the impact of LINC00673 gene polymorphisms on the risk and progression of OSCC. Three LINC00673 single-nucleotide polymorphisms (SNPs), including rs11655237, rs9914618, and rs6501551, were evaluated in 1231 OSCCC cases and 1194 cancer-free controls. We did not observe any significant association of three individual SNPs with the risk of OSCC between the case and control group. However, while assessing the clinicopathological parameters, patients carrying at least one minor allele of rs9914618 (GA and AA; OR, 1.286; 95% CI, 1.008–1.642; p = 0.043) were found to develop lymph node metastasis more often compared to those who are homozygous for the major allele. Further stratification analyses revealed that this genetic correlation with increased risk of lymphatic spread was further fortified in habitual betel quid chewers (OR, 1.534; 95% CI, 1.160–2.028; p = 0.003) or smokers (OR, 1.320; 95% CI, 1.013–1.721; p = 0.040). Moreover, through analyzing the dataset from The Cancer Genome Atlas (TCGA), we found that elevated LINC00673 levels were associated with the development of large tumors in patients with head and neck squamous cell carcinoma and the risk of lymphatic spread in smokers. These data demonstrate a joint effect of LINC00673 rs9914618 with betel nut chewing or smoking on the progression of oral cancer.


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1493
Author(s):  
Camila Meirelles S. Silva ◽  
Mateus C. Barros-Filho ◽  
Deysi Viviana T. Wong ◽  
Julia Bette H. Mello ◽  
Livia Maria S. Nobre ◽  
...  

Colorectal cancer (CRC) is a disease with high incidence and mortality. Colonoscopy is a gold standard among tests used for CRC traceability. However, serious complications, such as colon perforation, may occur. Non-invasive diagnostic procedures are an unmet need. We aimed to identify a plasma microRNA (miRNA) signature for CRC detection. Plasma samples were obtained from subjects (n = 109) at different stages of colorectal carcinogenesis. The patients were stratified into a non-cancer (27 healthy volunteers, 17 patients with hyperplastic polyps, 24 with adenomas), and a cancer group (20 CRC and 21 metastatic CRC). miRNAs (381) were screened by TaqMan Low-Density Array. A classifier based on four differentially expressed miRNAs (miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p) was able to discriminate cancer versus non-cancer cases. The overexpression of these miRNAs was confirmed by RT-qPCR, and a cross-study validation step was implemented using eight data series retrieved from Gene Expression Omnibus (GEO). In addition, another external data validation using CRC surgical specimens from The Cancer Genome Atlas (TCGA) was carried out. The predictive model’s performance in the validation set was 76.5% accuracy, 59.4% sensitivity, and 86.8% specificity (area under the curve, AUC = 0.716). The employment of our model in the independent publicly available datasets confirmed a good discrimination performance in five of eight datasets (median AUC = 0.823). Applying this algorithm to the TCGA cohort, we found 99.5% accuracy, 99.7% sensitivity, and 90.9% specificity (AUC = 0.998) when the model was applied to solid colorectal tissues. Overall, we suggest a novel signature of four circulating miRNAs, i.e., miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p, as a predictive tool for the detection of CRC.


2021 ◽  
Vol 124 (9) ◽  
pp. 1516-1523
Author(s):  
Lindy M. Kregting ◽  
Sylvia Kaljouw ◽  
Lucie de Jonge ◽  
Erik E. L. Jansen ◽  
Elleke F. P. Peterse ◽  
...  

Abstract Background Many breast, cervical, and colorectal cancer screening programmes were disrupted due to the COVID-19 pandemic. This study aimed to estimate the effects of five restart strategies after the disruption on required screening capacity and cancer burden. Methods Microsimulation models simulated five restart strategies for breast, cervical, and colorectal cancer screening. The models estimated required screening capacity, cancer incidence, and cancer-specific mortality after a disruption of 6 months. The restart strategies varied in whether screens were caught up or not and, if so, immediately or delayed, and whether the upper age limit was increased. Results The disruption in screening programmes without catch-up of missed screens led to an increase of 2.0, 0.3, and 2.5 cancer deaths per 100 000 individuals in 10 years in breast, cervical, and colorectal cancer, respectively. Immediately catching-up missed screens minimised the impact of the disruption but required a surge in screening capacity. Delaying screening, but still offering all screening rounds gave the best balance between required capacity, incidence, and mortality. Conclusions Strategies with the smallest loss in health effects were also the most burdensome for the screening organisations. Which strategy is preferred depends on the organisation and available capacity in a country.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Lukasz Markiewicz ◽  
Dariusz Pytel ◽  
Bartosz Mucha ◽  
Katarzyna Szymanek ◽  
Jerzy Szaflik ◽  
...  

The aim of presented work was to analyze the impact of particular polymorphic changes in the promoter regions of the -1607 1G/2GMMP1, -1562 C/TMMP9, -82 A/GMMP12, -511 C/TIL-1β, and 372 T/CTIMP1genes on their expression level in POAG patients. Blood and aqueous humor samples acquired from 50 patients with POAG and 50 control subjects were used for QPCR and protein levels analysis by ELISA.In vivopromoter activity assays were carried on HTM cells using dual luciferase assay. All studied subjects underwent ophthalmic examination, including BCVA, intraocular pressure, slit-lamp examination, gonioscopy, HRT, and OCT scans. Patients with POAG are characterized by an increased mRNA expression ofMMP1,MMP9,MMP12, andIL-1βgenes as compared to the control group (P<0.001). Aqueous humor acquired from patients with POAG displayed increased protein expression of MMP1, MMP9, MMP12, and IL-1βcompared to the control group (P<0.001). Allele -1607 1G ofMMP1gene possesses only 42,91% of the -1607 2G allele transcriptional activity and allele -1562 C ofMMP9gene possesses only 21,86% of the -1562 T allele. Increased expression levels of metalloproteinases can be considered as a risk factor for the development of POAG.


2018 ◽  
Vol 19 (12) ◽  
pp. 3711 ◽  
Author(s):  
Ovidiu Balacescu ◽  
Daniel Sur ◽  
Calin Cainap ◽  
Simona Visan ◽  
Daniel Cruceriu ◽  
...  

Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies with a high incidence and mortality rate. An essential challenge in colorectal cancer management is to identify new prognostic factors that could better estimate the evolution and treatment responses of this disease. Considering their role in cancer development, progression and metastasis, miRNAs have become an important class of molecules suitable for cancer biomarkers discovery. We performed a systematic search of studies investigating the role of miRNAs in colorectal progression and liver metastasis published until October 2018. In this review, we present up-to-date information regarding the specific microRNAs involved in CRC development, considering their roles in alteration of Wnt/βcatenin, EGFR, TGFβ and TP53 signaling pathways. We also emphasize the role of miRNAs in controlling the epithelial–mesenchymal transition of CRC cells, a process responsible for liver metastasis in a circulating tumor cell-dependent manner. Furthermore, we discuss the role of miRNAs transported by CRC-derived exosomes in mediating liver metastases, by preparing the secondary pre-metastatic niche and in inducing liver carcinogenesis in a Dicer-dependent manner.


2019 ◽  
pp. 1-10
Author(s):  
Gregory C. Knapp ◽  
Olusegun I. Alatise ◽  
Olalekan O. Olasehinde ◽  
Ademola Adeyeye ◽  
Omobolaji O. Ayandipo ◽  
...  

PURPOSE The global burden of colorectal cancer (CRC) will continue to increase for the foreseeable future, largely driven by increasing incidence and mortality in low- and middle-income countries (LMICs) such as Nigeria. METHODS We used the Wilson-Jungner framework (1968) to review the literature relevant to CRC screening in Nigeria and propose areas for future research and investment. RESULTS Screening is effective when the condition sought is both important and treatable within the system under evaluation. The incidence of CRC is likely increasing, although the exact burden of disease in Nigeria remains poorly understood and access to definitive diagnosis and treatment has not been systematically quantified. In high-income countries (HICs), CRC screening builds on a well-known natural history. In Nigeria, a higher proportion of CRC seems to demonstrate microsatellite instability, which is dissimilar to the molecular profile in HICs. Prospective trials, tissue banking, and next-generation sequencing should be leveraged to better understand these potential differences and the implications for screening. Fecal immunochemical test for hemoglobin (FIT) is recommended for LMICs that are considering CRC screening. However, FIT has not been validated in Nigeria, and questions about the impact of high ambient temperature, endemic parasitic infection, and feasibility remain unanswered. Prospective trials are needed to validate the efficacy of stool-based screening, and these trials should consider concomitant ova and parasite testing. CONCLUSION Using the Wilson-Jungner framework, additional work is needed before organized CRC screening will be effective in Nigeria. These deficits can be addressed without missing the window to mitigate the increasing burden of CRC in the medium to long term.


Glycobiology ◽  
2019 ◽  
Vol 29 (10) ◽  
pp. 684-695 ◽  
Author(s):  
Giulia Venturi ◽  
Inês Gomes Ferreira ◽  
Michela Pucci ◽  
Manuela Ferracin ◽  
Nadia Malagolini ◽  
...  

AbstractCancer-associated glycan structures can be both tumor markers and engines of disease progression. The structure Siaα2,6Galβ1,4GlcNAc (Sia6LacNAc), synthesized by sialyltransferase ST6GAL1, is a cancer-associated glycan. Although ST6GAL1/Sia6LacNAc are often overexpressed in colorectal cancer (CRC), their biological and clinical significance remains unclear. To get insights into the clinical relevance of ST6GAL1 expression in CRC, we interrogated The Cancer Genome Atlas with mRNA expression data of hundreds of clinically characterized CRC and normal samples. We found an association of low ST6GAL1 expression with microsatellite instability (MSI), BRAF mutations and mucinous phenotype but not with stage, response to therapy and survival. To investigate the impact of ST6GAL1 expression in experimental systems, we analyzed the transcriptome and the phenotype of the CRC cell lines SW948 and SW48 after retroviral transduction with ST6GAL1 cDNA. The two cell lines display the two main pathways of CRC transformation: chromosomal instability and MSI, respectively. Constitutive ST6GAL1 expression induced much deeper transcriptomic changes in SW948 than in SW48 and affected different genes in the two cell lines. ST6GAL1 expression affected differentially the tyrosine phosphorylation induced by hepatocyte growth factor, the ability to grow in soft agar, to heal a scratch wound and to invade Matrigel in the two cell lines. These results indicate that the altered expression of a cancer-associated glycosyltransferase impacts the gene expression profile, as well as the phenotype, although in a cancer subtype-specific manner.


2007 ◽  
Vol 25 (19) ◽  
pp. 2702-2708 ◽  
Author(s):  
Thomas Küchler ◽  
Beate Bestmann ◽  
Stefanie Rappat ◽  
Doris Henne-Bruns ◽  
Sharon Wood-Dauphinee

Purpose The impact of psychotherapeutic support on survival for patients with gastrointestinal cancer undergoing surgery was studied. Patients and Methods A randomized controlled trial was conducted in cooperation with the Departments of General Surgery and Medical Psychology, University Hospital of Hamburg, Germany, from January 1991 to January 1993. Consenting patients (N = 271) with a preliminary diagnosis of cancer of the esophagus, stomach, liver/gallbladder, pancreas, or colon/rectum were stratified by sex and randomly assigned to a control group that received standard care as provided on the surgical wards, or to an experimental group that received formal psychotherapeutic support in addition to routine care during the hospital stay. From June 2003 to December 2003, the 10-year follow-up was conducted. Survival status for all patients was determined from our own records and from three external sources: the Hamburg cancer registry, family doctors, and the general citizen registration offices. Results Kaplan-Meier survival curves demonstrated better survival for the experimental group than the control group. The unadjusted significance level for group differences was P = .0006 for survival to 10 years. Cox regression models that took TNM staging or the residual tumor classification and tumor site into account also found significant differences at 10 years. Secondary analyses found that differences in favor of the experimental group occurred in patients with stomach, pancreatic, primary liver, or colorectal cancer. Conclusion The results of this study indicate that patients with gastrointestinal cancer, who undergo surgery for stomach, pancreatic, primary liver, or colorectal cancer, benefit from a formal program of psychotherapeutic support during the inpatient hospital stay in terms of long-term survival.


2004 ◽  
Vol 29 (4) ◽  
pp. 447-460 ◽  
Author(s):  
Simon J. Lees ◽  
Frank W. Booth

Sedentary death syndrome (SeDS) is a major public health burden due to its causing multiple chronic diseases and millions of premature deaths each year. Despite the impact of physical inactivity, very little is known about the actual causes of physical inactivity-induced chronic diseases. It is important to study the mechanisms underlying molecular changes related to physical inactivity in order to better understand the scientific basis of individualized exercise prescription and the rapies for chronic diseases, and to support improved public health efforts by providing molecular proof that physical inactivity is an actual cause of chronic diseases. Physical activity has a genetic basis. A subpopulation of genes, which have functioned to support physical activity for survival through most of humankind's existence, require daily exercise to maintain long-term health and vitality. Type 2 diabetes (T2D) is an example of a SeDS condition, as it is almost entirely preventable with physical activity. To determine the true role of physical inactivity in the development and progression of T2D, information is presented which indicates that comparisons should be made to physically active controls, rather than sedentary controls, as this population is the healthiest. Use of sedentary subjects as the control group has led to potentially misleading interpretations. If physically active individuals were designated as the control group, a different interpretation would have been drawn. It is thought that there is no difference in GLUT4 concentration between T2D and sedentary groups. However, GLUT4 expression is higher in active controls than in sedentary and T2D groups. Therefore, to obtain causal mechanisms for SeDS in order to allow for scientifically based prevention and therapy strategies, physically active subjects must serve as the control group. Key words: physical inactivity, chronic diseases, diabetes, glucose


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