scholarly journals SNP Mutation‐related Genes in Colon Cancer for Monitoring and Prognosis of Patients: A Study Based on the TCGA Database

2020 ◽  
Author(s):  
Xin Liao ◽  
jian li ◽  
Yuxiang Chen ◽  
Haibo Ding ◽  
Chen Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cause Of Death ◽  
Immune Cell ◽  
Tumor Therapy ◽  
Molecular Pathogenesis ◽  
Related Data ◽  
The Core ◽  
Cancer Tumor ◽  
Core Genes

Abstract Background: Cancer is still the leading cause of death in humans, and the fourth leading cause of death is colorectal cancer. Tumor bioinformatics has been developing in recent years, the prognosis and quality of life of patients can be improved by using relevant tools to understand the molecular pathogenesis of colorectal cancer and related prognostic markers. Methods: In this study, Bioinformatics analysis of the snp-related data of colon cancer patients from the TCGA database, it was found that the expression levels of 4 mutated genes (CTTNBP2,DAPK1, DMXL1,SPTBN2) were significantly different from those of wild type and their prognosis. In order to explore how the core genes affect the prognosis of patients, the gene expression of these core genes was analyzed. Results: It was found that the core genes are related to a variety of cancer-related pathway genes, including pi3k-akt pathway and TSC/mTOR pathway. Drug sensitivity analysis showed that SPTBN2 could be inhibited by a variety of drugs, including austocystin D, afatinib, and belinostat. Tumor immunity is closely related to tumor therapy. Through the analysis of immune infiltration of core genes, it was found that DAPK1 and DMXL2 were associated with a variety of immune cell infiltration. Conclusion: Therefore, the detection of genetic mutations and related expressions may be significant in predicting the prognosis of patients with colon cancer. Through the study of high-throughput information excavating, it was discovered that the molecular pathogenesis and prognosis of patients with colon cancer were helpful to the bioinformatics theory.

scholarly journals Primary and Secondary Prevention of Colorectal Cancer

2014 ◽  
Vol 7 ◽  
pp. CGast.S14039 ◽  
Author(s):  
Pedro J. Tárraga López ◽  
Juan Solera Albero ◽  
José Antonio Rodríguez-Montes
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Early Detection ◽  
Secondary Prevention ◽  
Cause Of Death ◽  
Meta Analysis ◽  
Brown Rice ◽  
Primary And Secondary Prevention ◽  
The Third ◽  
Diet And Lifestyle

Introduction Cancer is a worldwide problem as it will affect one in three men and one in four women during their lifetime. Colorectal cancer (CRC) is the third most frequent cancer in men, after lung and prostate cancer, and is the second most frequent cancer in women after breast cancer. It is also the third cause of death in men and women separately, and is the second most frequent cause of death by cancer if both genders are considered together. CRC represents approximately 10% of deaths by cancer. Modifiable risk factors of CRC include smoking, physical inactivity, being overweight and obesity, eating processed meat, and drinking alcohol excessively. CRC screening programs are possible only in economically developed countries. However, attention should be paid in the future to geographical areas with ageing populations and a western lifestyle. 19 , 20 Sigmoidoscopy screening done with people aged 55-64 years has been demonstrated to reduce the incidence of CRC by 33% and mortality by CRC by 43%. Objective To assess the effect on the incidence and mortality of CRC diet and lifestyle and to determine the effect of secondary prevention through early diagnosis of CRC. Methodology A comprehensive search of Medline and Pubmed articles related to primary and secondary prevention of CRC and subsequently, a meta-analysis of the same blocks are performed. Results 225 articles related to primary or secondary prevention of CRC were retrieved. Of these 145 were considered valid on meta-analysis: 12 on epidemiology, 56 on diet and lifestyle, and over 77 different screenings for early detection of CRC. Cancer is a worldwide problem as it will affect one in three men and one in four women during their lifetime. There is no doubt whatsoever which environmental factors, probably diet, may account for these cancer rates. Excessive alcohol consumption and cholesterol-rich diet are associated with a high risk of colon cancer. A diet poor in folic acid and vitamin B6 is also associated with a higher risk of developing colon cancer with an overexpression of p53. Eating pulses at least three times a week lowers the risk of developing colon cancer by 33%, after eating less meat, while eating brown rice at least once a week cuts the risk of CRC by 40%. These associations suggest a dose–response effect. Frequently eating cooked green vegetables, nuts, dried fruit, pulses, and brown rice has been associated with a lower risk of colorectal polyps. High calcium intake offers a protector effect against distal colon and rectal tumors as compared with the proximal colon. Higher intake of dairy products and calcium reduces the risk of colon cancer. Taking an aspirin (ASA) regularly after being diagnosed with colon cancer is associated with less risk of dying from this cancer, especially among people who have tumors with COX-2 overexpression. 16 Nonetheless, these data do not contradict the data obtained on a possible genetic predisposition, even in sporadic or non-hereditary CRC. CRC is susceptible to screening because it is a serious health problem given its high incidence and its associated high morbidity/mortality. Conclusions (1) Cancer is a worldwide problem. (2) A modification of diet and lifestyle could reduce morbidity and mortality. (3) Early detection through screening improves prognosis and reduces mortality.

scholarly journals SERPINE1 associated with remodeling of the tumor microenvironment in colon cancer progression: a novel therapeutic target

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shaokun Wang ◽  
Li Pang ◽  
Zuolong Liu ◽  
Xiangwei Meng
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Immune Cells ◽  
Immune Cell ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
The Relationship

Abstract Background The change of immune cell infiltration essentially influences the process of colorectal cancer development. The infiltration of immune cells can be regulated by a variety of genes. Thus, modeling the immune microenvironment of colorectal cancer by analyzing the genes involved can be more conducive to the in-depth understanding of carcinogenesis and the progression thereof. Methods In this study, the number of stromal and immune cells in malignant tumor tissues were first estimated by using expression data (ESTIMATE) and cell-type identification with relative subsets of known RNA transcripts (CIBERSORT) to calculate the proportion of infiltrating immune cell and stromal components of colon cancer samples from the Cancer Genome Atlas database. Then the relationship between the TMN Classification and prognosis of malignant tumors was evaluated. Results By investigating differentially expressed genes using COX regression and protein-protein interaction network (PPI), the candidate hub gene serine protease inhibitor family E member 1 (SERPINE1) was found to be associated with immune cell infiltration. Gene Set Enrichment Analysis (GSEA) further projected the potential pathways with elevated SERPINE1 expression to carcinogenesis and immunity. CIBERSORT was subsequently utilized to investigate the relationship between the expression differences of SERPINE1 and immune cell infiltration and to identify eight immune cells associated with SERPINE1 expression. Conclusion We found that SERPINE1 plays a role in the remodeling of the colon cancer microenvironment and the infiltration of immune cells.

Combined PD-1 inhibition (Pembrolizumab) and CCR5 inhibition (Maraviroc) for the treatment of refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC): First results of the PICCASSO phase I trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3010-3010
Author(s):  
Georg Martin Haag ◽  
Niels Halama ◽  
Christoph Springfeld ◽  
Barbara Grün ◽  
Leonidas Apostolidis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune System ◽  
Phase I ◽  
Phase I Trial ◽  
Immune Cell ◽  
Adaptive Immune System ◽  
Current Phase ◽  
Clinical Activity ◽  
The Core ◽  
Special Event

3010 Background: Checkpoint inhibition using PD-1/PD-L1 inhibitors does not show clinically relevant activity in MSS/pMMR (Mismatch Repair Proficient) colorectal cancer. Previous work showed that inhibition of CCR5 (C-C chemokine receptor type 5) leads to a macrophage re-polarization towards M1 macrophages within the tumor microenvironment which directly affects immune cell infiltrates. The current phase I trial explores a combined modification of the innate immune system (by CCR 5 blockade) and the adaptive immune system (by PD-1 inhibition) in the treatment of MSS CRC. Methods: 20 patients with metastatic MSS/pMMR colorectal cancer with failure of fluoropyrimidines, oxaliplatin, irinotecan, VEGF antibodies and EGFR antibodies (in ras WT patients) received pembrolizumab 200 mg q21d and maraviroc 300 mg bid cont. for 8 cycles, followed by pembrolizumab monotherapy for a maximum of 24 additional cycles. Imaging was performed every nine weeks (RECIST and irRECIST criteria). Primary endpoint was the feasibility rate (rate of patients receiving the protocol treatment during the core treatment without special event: treatment-related Grade ≥ 3 immune-related abnormalities, treatment-related Grade ≥ 4 AEs or any toxicity-related premature withdrawal of treatment). Secondary endpoints included safety/toxicity, ORR, PFS and OS. Results: 20 patients were enrolled. The median number of applied cycles was 3.5 for pembrolizumab and 3.5 for maraviroc. Two patients completed the core treatment period with pembrolizumab and started maintenance treatment. The feasibility rate was 94.7% (90% CI 77.4 to 99.7%), with one patient experiencing a special event. Except this grade 4 event (hyperglycemia) no ≥ 3 treatment-related toxicities were observed. According to irRECIST criteria one patient showed a partial response and one a stable disease as best response, resulting in an irDCR of 10.5%. Median PFS according to irRECIST was 2 months (CI 95%, 2 to 3), median OS 9 months (CI 95%, 6 to 20). Conclusions: Therapy with pembrolizumab and maraviroc was feasible and showed a beneficial toxicity pattern. Clinical activity in MSS CRC patients was limited, however prolonged disease stabilizations were observed in single patients and overall survival was higher than expected in this heavily pretreated population. Clinical trial information: NCT03274804 .

scholarly journals Colon Cancer Classification and Prognosis Prediction Based on Genomics Multi-features

2021 ◽  
Author(s):  
Jiasheng Xu ◽  
Kaili Liao ◽  
Chengfeng Wu ◽  
Qijun Yang ◽  
Hongping Wan ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Immune Cell ◽  
Evaluation Model ◽  
Lasso Regression ◽  
Data Set ◽  
Prognosis Prediction ◽  
External Data ◽  
Core Genes ◽  
Prognosis Evaluation

Abstract Background: To classify colon cancer and predict the prognosis of patients with multiple characteristics of the genome.Methods: We used the mRNA expression profile data and mutation maf files of colon cancer patients in the TCGA database to calculate the TMB value of patients. Combined with CNV, MSI, and corresponding clinical information, the patients were clustered by the "K-means" method to identify different molecular subtypes of colon cancer. Comparing the differences of prognosis, and immune cell infiltration, and other indicators among patients in each subgroup, we used COX and lasso regression analysis to screen out the prognosis difference genes among subgroups and construct the prognosis prediction model. We used the external data set to verify the model, and carried out the hierarchical analysis of the model to compare the immune infiltration of patients in the high and low-risk groups. And detected the expression differences of core genes in tumor tissues of patients with different clinical stages by qPCR and immunohistochemistry.Results: We successfully calculated the TMB value and divided the patients into three subgroups. The prognosis of the second subgroup was significantly different from the other two groups. The mmunoinfiltration analysis showed that the expression of NK.cells.resting increased in cluster1 and cluster 3, and the expression of T.cells.CD4.memory.resting increased in cluster3. By analyzing the differences among subgroups, we screened out eight core genes related to prognoses, such as HYAL1, SPINK4, EREG, and successfully constructed a patient prognosis evaluation model. The test results of the external data set shows that the model can accurately predict the prognosis of patients; Compared with risk factors such as TNM stage and age, the risk score of the model has higher evaluation efficiency. The experimental results confirmed that the differential expression of eight core genes was basically consistent with the model evaluation results.Conclusion: Colon cancer patients were further divided into three subtypes by using genomic multi-features, and eight-core genes related to prognosis were screened out and the prognosis evaluation model was successfully constructed. With external data and experiments, it verified that the model had good evaluation efficiency.

scholarly journals CTDSP1 inhibitor rabeprazole regulates DNA-PKcs dependent topoisomerase I degradation and irinotecan drug resistance in colorectal cancer

2020 ◽  
Author(s):  
Hiroya Matsuoka ◽  
Koji Ando ◽  
Emma J Swayze ◽  
Elizabeth C Unan ◽  
Joseph Mathew ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Drug Resistance ◽  
Topoisomerase I ◽  
Resistance Mechanism ◽  
Rapid Rate ◽  
Rapid Degradation ◽  
The Core ◽  
Upstream Regulator ◽  
Kinase Cascade

AbstractIrinotecan specifically targets topoisomerase I (topoI), and is used to treat various solid tumors, but only 13-32% of patients respond to the therapy. Now, it is understood that the rapid rate of topoI degradation in response to irinotecan causes irinotecan resistance. We have published that the deregulated DNA-PKcs kinase cascade ensures rapid degradation of topoI and is at the core of the drug resistance mechanism of topoI inhibitors, including irinotecan. We also identified CTD small phosphatase 1 (CTDSP1) (a nuclear phosphatase) as a primary upstream regulator of DNA-PKcs in response to topoI inhibitors. Previous reports showed that rabeprazole, a proton pump inhibitor (PPI) inhibits CTDSP1 activity. The purpose of this study was to confirm the effects of rabeprazole on CTDSP1 activity and its impact on colon cancer. Using HCT116 and HT29, with high and low CTDSP1 expression respectively and a retrospective analysis of patients receiving irinotecan with or without rabeprazole have indicated the effect of CTDSP1 in irinotecan response. These results indicate that CTDSP1 promotes sensitivity to irinotecan and rabeprazole prevents this effect, resulting in drug resistance. To ensure the best chance at effective treatment, rabeprazole may not be a suitable PPI for cancer patients treated with irinotecan.

scholarly journals The encounter of tumor and SARS-CoV-2: Pathological findings in a patient with colon cancer and COVID-19

2020 ◽  
Author(s):  
Weixiang Zhong ◽  
Jun Li ◽  
Mei Kong ◽  
Qiqi Gao ◽  
Xiaodong Teng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
T Cell ◽  
Tissue Microarrays ◽  
Cd8 T Cell ◽  
Cancer Tissue ◽  
Surgical Specimen ◽  
Positive Rate ◽  
Cancer Tumor ◽  
Cell Proportion

Abstract As coronavirus disease 2019 (COVID-19) spreads worldwide, there have been few reports of infections among the cancer population, although more than six million cases have been confirmed. Here we studied a surgical specimen from a patient with colon cancer and COVID-19 and two tissue microarrays comprising 103 colorectal cancer and 108 enterocyte cases pathologically. The results showed that, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid antibody was positively expressed in colon cancer tissues. Moreover, the angiotensin converting enzyme 2 (ACE2) was overexpressed in both colorectal cancer tissue microarray and tumor tissue from this patient, with a positive rate as high as 93.2%. Finally, this case of SARS-CoV-2 infection in colon cancer tumor microenvironment (TME) is a failure of immune homeostasis, due to the decrease in TIA + and Granzyme B+ (GrB) CD8 + T cell proportion and the increase in PD-1 + CD8 + T cell proportion. In summary, we speculate that these three factors may have contributed significantly to infection risk and severity in the patient.

scholarly journals Predicting MicroRNA Target Genes and Identifying Hub Genes in IIA Stage Colon Cancer Patients Using Bioinformatics Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Zhiyong Dong ◽  
Wei Lin ◽  
Stacy A. Kujawa ◽  
Shike Wu ◽  
Cunchuan Wang
Keyword(s):  
Colon Cancer ◽  
Signaling Pathway ◽  
Target Genes ◽  
Kegg Pathway ◽  
System Development ◽  
Nervous System Development ◽  
Hub Genes ◽  
The Core ◽  
Upregulated Genes ◽  
Core Genes

Background. Colon cancer is a heterogeneous disease, differing in clinical symptoms, epigenetics, and prognosis for each individual patient. Identifying the core genes is important for early diagnoses and it provides a more precise method for treating colon cancer. Materials and Methods. In this study, we wanted to pinpoint these core genes so we obtained GSE101502 microRNA profiles from the GEO database, which resulted in 17 differential expressed microRNAs that were identified by GEO2R analysis. Then, 875 upregulated and 2920 downregulated target genes were predicted by FunRich. GO and KEGG pathway were used to do enrich analysis. Results. GO analysis indicated that upregulated genes were significantly enriched in the regulation of cell communication and signaling and in nervous system development, while the downregulated genes were significantly enriched in nervous system development and regulation of transcription from the RNA polymerase II promoter. KEGG pathway analysis suggested that the upregulated genes were enriched in axon guidance, MAPK signaling pathway, and endocytosis, while the downregulated genes existed in pathways in cancer, focal adhesion, and PI3K-Akt signaling pathway. The top four molecules including 82 hub genes were identified from the PPI network and involved in endocytosis, spliceosome, TGF-beta signaling pathway, and lysosome. Finally, NUDT21, GNB1, CLINT1, and COL1A2 core gene were selected due to their correlation with the prognosis of IIA stage colon cancer. Conclusion. this study suggested that NUDT21, GNB1, CLINT1, and COL1A2 might be the core genes for colon cancer that play an important role in the development and prognosis of IIA stage colon cancer.

scholarly journals Key Biomarkers Within the Colorectal Cancer Related Inflammatory Microenvironment

2020 ◽  
Author(s):  
Valentin Calu ◽  
Adriana Ionescu ◽  
Loredana Stanca ◽  
Ovidiu Geicu ◽  
Florin Iordache ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Tumor Resection ◽  
Surgical Care ◽  
Magnetic Bead ◽  
Inflammatory Factors ◽  
Tissue Samples ◽  
Inflammatory Microenvironment ◽  
Starting Point ◽  
Cancer Tumor

Abstract The necessity of therapeutic approaches focused on the inflammatory microenvironment of colorectal cancer (CRC) is becoming more and more apparent, both in order to improve post-surgical care and subsequent therapeutic strategies, and also for better quality of life for the patients. We have investigated a panel of 39 inflammatory factors using a multiplex magnetic bead-based immunoassay, in relation with CEA and CA19-9, classical tumor markers and the expression levels of pErk, occludin, and STAT1 and STAT3 transcriptional factors. Within the tumor and paired normal tissue samples collected during tumor resection surgery, we have identified 32 biomarkers displaying statistically significant differences. Several relevant correlations have been observed in a combined multi-type correlation matrix. Chitinase 3-like 1 seems to be a trigger for activation pathways for tumor growth and metastasis. Through IL-22 and IL1β, IL-8 correlates indirectly with CA19-9 and CEA, respectively. We also emphasize the diminished APRIL and high BAFF levels in colon cancer tumor tissue, which is quite unique. The strong correlation between APRIL, BAFF, IL-8 and MMP2 recommends these as combined targets in immunotherapies for colon cancer treatment, and indicates the marker quartet may serve as a starting point in colon cancer screening.

scholarly journals Identified and Validated the Characterization of the Colorectal Cancer Tumor Immune Microenvironment

2020 ◽  
Author(s):  
Peng Han ◽  
yu De Chen ◽  
Feng Yang
Keyword(s):  
Colorectal Cancer ◽  
Immune Cell ◽  
Expression Profiles ◽  
Cell Types ◽  
Small Subset ◽  
Data Sets ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Cancer Tumor ◽  
Microsatellite Stability

Abstract Background While the administration of immunotherapy can facilitate the development of durable anti-tumor immunity in certain colorectal cancer (CRC) patients.This study was therefore designed to conduct a robust analysis of the CRC immune microenvironment to identify specific genes and pathways that can be targeted in an effort to achieve more effective immunotherapy outcomes. Methods Using five Independent data sets, we analyzed expression profiles associated with 29 different immune signatures, and we used these profiles to guide the hierarchical clustering of CRC samples based on their immune microenvironmental composition. Results We were able to cluster our CRC samples based on whether they had exhibited high, medium, or low levels of infiltration by immune cell types associated with tumor clearance (Immunity_H, Immunity_M, and Immunity_L, respectively). Samples in the Immunity_H subset exhibited a “hot” immune microenvironment, with higher stromal scores, higher immune scores, and lower tumor purity. The microsatellite instability (MSI) group included the majority of the Immunity_H samples, whereas most Immunity_M and Immunity_L samples were incorporated into the microsatellite stability (MSS) .The vast majority of patients with KRAS mutations were in the Immunity_L and MSS groups, whereas the majority of patients exhibiting BRAF V600E mutations were found in the Immunity_H and MSI-H samples. TMB high samples included a majority of the Immunity_H samples and a small subset of the Immunity_M samples. Conclusions Our results identify three reproducibly validated immune subtypes of CRC tumor samples, potentially offering valuable insights that may guide the immunotherapeutic treatment of these patients.

scholarly journals Analysis of core genes for colorectal cancer prognosis based on immune and stromal scores

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12452
Author(s):  
Yi Zhu ◽  
Yuan Zhou ◽  
HongGang Jiang ◽  
ZhiHeng Chen ◽  
BoHao Lu
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Differentially Expressed Genes ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Ppi Network ◽  
The Core ◽  
Regulatory Effects ◽  
Core Genes

Background Colorectal cancer (CRC) is one of the most common malignancies.An early diagnosis and an accurate prognosis are major focuses of CRC research. Tumor microenvironment cells and the extent of infiltrating immune and stromal cells contribute significantly to the tumor prognosis. Methods Immune and stromal scores were calculated based on the ESTIMATE algorithm using the sample expression profile of the The Cancer Genome Atlas (TCGA) database. GSE102479 was used as the validation database. Differentially expressed genes whose expression was significantly associated with the prognosis of CRC patients were identified based on the immune matrix score. Survival analysis was conducted on the union of the differentially expressed genes. A protein–protein interaction (PPI) network was constructed using the STRING database to identify the closely connected modules. To conduct functional enrichment analysis of the relevant genes, GO and KEGG pathway analyses were performed with Cluster Profiler. Pivot analysis of the ncRNAs and TFs was performed by using the RAID2.0 database and TRRUST v2 database. TF-mRNA regulatory relationships were analyzed in the TRRUST V2 database. Hubgene targeting relationships were screened in the TargetScan, miRTarBase and miRDB databases. The SNV data of the hub genes were analyzed by using the R maftools package. A ROC curve was drawn based on the TCGA database. The proportion of immune cells was estimated using CIBERSORT and the LM22 feature matrix. Results The results showed that the matrix score was significantly correlated with colorectal cancer stage T. A total of 789 differentially expressed genes and 121 survival-related prognostic genes were identified. The PPI network showed that 22 core genes were related to the CRC prognosis. Furthermore, four ncRNAs that regulated the core prognosis genes, 11 TFs with regulatory effects on the core prognosis genes, and two drugs, quercetin and pseudoephedrine, that have regulatory effects on colorectal cancer were also identified. Conclusions We obtained a list of tumor microenvironment-related genes for CRC patients. These genes could be useful for determining the prognosis of CRC patients. To confirm the function of these genes, additional experiments are necessary.

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