scholarly journals High expression of DNA damage-inducible transcript 4 (DDIT4) is associated with advanced pathological features in the patients with colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fahimeh Fattahi ◽  
Leili Saeednejad Zanjani ◽  
Zohreh Habibi Shams ◽  
Jafar Kiani ◽  
Mitra Mehrazma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Prognostic Significance ◽  
Tissue Microarrays ◽  
Survival Outcomes ◽  
Hub Genes ◽  
Kegg Pathways ◽  
Normal Tissues ◽  
Nuclear Expression ◽  
Pathways Analysis

AbstractDNA damage-inducible transcript 4 (DDIT4) is induced in various cellular stress conditions. This study was conducted to investigate expression and prognostic significance of DDIT4 protein as a biomarker in the patients with colorectal cancer (CRC). PPI network and KEGG pathway analysis were applied to identify hub genes among obtained differentially expressed genes in CRC tissues from three GEO Series. In clinical, expression of DDIT4 as one of hub genes in three subcellular locations was evaluated in 198 CRC tissues using immunohistochemistry method on tissue microarrays. The association between DDIT4 expression and clinicopathological features as well as survival outcomes were analyzed. Results of bioinformatics analysis indicated 14 hub genes enriched in significant pathways according to KEGG pathways analysis among which DDIT4 was selected to evaluate CRC tissues. Overexpression of nuclear DDIT4 protein was found in CRC tissues compared to adjacent normal tissues (P = 0.003). Furthermore, higher nuclear expression of DDIT4 was found to be significantly associated with the reduced tumor differentiation and advanced TNM stages (all, P = 0.009). No significant association was observed between survival outcomes and nuclear expression of DDIT4 in CRC cases. Our findings indicated higher nuclear expression of DDIT4 was significantly associated with more aggressive tumor behavior and more advanced stage of disease in the patients with CRC.

scholarly journals Genomic Expression Profiling of Colorectal Cancer in Silico

2021 ◽  
Author(s):  
Feifei Liu ◽  
Yu Wang ◽  
Wenxue Li ◽  
Diancheng Li ◽  
Yuwei Xin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Analysis ◽  
Mrna Expression ◽  
Differentially Expressed Genes ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Analysis Tool ◽  
Hub Genes ◽  
Normal Tissues

Abstract Background: Colorectal cancer (CRC) is one of the most common malignancies of the digestive system; the progression and prognosis of which are affected by a complicated network of genes and pathways. The aim of this study was to identify potential hub genes associated with the progression and prognosis of colorectal cancer (CRC).Methods: We obtained gene expression profiles from GEO database to search differentially expressed genes (DEGs) between CRC tissues and normal tissue. Subsequently, we conducted a functional enrichment analysis, generated a protein–protein interaction (PPI) network to identify the hub genes, and analyzed the expression validation of the hub genes. Kaplan–Meier plotter survival analysis tool was performed to evaluate the prognostic value of hub genes expression in CRC patients.Results: A total of 370 samples, involving CRC and normal tissues were enrolled in this article. 283 differentially expressed genes (DEGs), including 62 upregulated genes and 221 downregulated genes between CRC and normal tissues were selected. We finally filtered out 6 hub genes, including INSL5, MTIM, GCG, SPP1, HSD11B2, and MAOB. In the database of TCGA-COAD, the mRNA expression of INSL5, MT1M, HSD11B2, MAOB in tumor is lower than that in normal; the mRNA expression of SPP1 in tumor is higher than that in normal. In the HPA database, the expression of INSL5, GCG, HSD11B2, MAOB in tumor is lower than that in normal tissues; the expression of SPP1 in the tumor is higher than that in normal tissues. Survival analysis revealed that INSL5, GCG, SPP1 and MT1M may serve as prognostic biomarkers in CRC. Conclusions: We screened out six hub genes to predict the occurrence and prognosis of patients with CRC using bioinformatics methods, which may provide new targets and ideas for diagnosis, prognosis and individualized treatment for CRC.

scholarly journals Multiplexed 3D atlas of state transitions and immune interactions in colorectal cancer

2021 ◽  
Author(s):  
Jia-Ren Lin ◽  
Shu Wang ◽  
Shannon Coy ◽  
Madison A Tyler ◽  
Clarence Yapp ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Significance ◽  
Tissue Microarrays ◽  
Cell Types ◽  
Tissue Imaging ◽  
State Transitions ◽  
Small Scale ◽  
Spatial Gradients ◽  
Immunosuppressive Cell ◽  
Small Fields

Advanced solid cancers are complex assemblies of tumor, immune, and stromal cells that invade adjacent tissue and spread to distant sites. Here we use highly multiplexed tissue imaging, spatial statistics, and machine learning to identify cell types and states underlying morphological features of known diagnostic and prognostic significance in colorectal cancer. We find that a thorough spatial analysis requires imaging the entire tumor region, not small fields of view (e.g. those found in tissue microarrays). When this condition is met, the data reveal frequent transitions between histological archetypes (tumor grades and morphologies) correlated with molecular gradients. At the tumor invasive margin, where tumor, normal, and immune cells compete, localized features in 2D such as tumor buds and mucin pools are seen in 3D to be large connected structures having continuously varying molecular properties. Immunosuppressive cell-cell interactions also exhibit graded variation in type and frequency. Thus, whereas scRNA-Seq emphasizes discrete changes in tumor state, whole-specimen imaging reveals the presence of large- and small-scale spatial gradients analogous to those in developing tissues.

scholarly journals Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482090338
Author(s):  
Fabian Haak ◽  
Isabelle Obrecht ◽  
Nadia Tosti ◽  
Benjamin Weixler ◽  
Robert Mechera ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Cell ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Tumor Necrosis Factor Receptor ◽  
Tissue Microarrays ◽  
Cell Infiltration ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
Kaplan Meier

Objectives: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance. Methods: Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients’ survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration. Results: Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort. Conclusions: Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration.

scholarly journals Clinicopathological and Prognostic Significance of WW Domain Binding Protein 5 Expression in Papillary Thyroid Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Yangyang Qian ◽  
Zongfu Pan ◽  
Zhenying Guo ◽  
Xinyang Ge ◽  
Guowan Zheng ◽  
...  
Keyword(s):  
Binding Protein ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Tissue Microarrays ◽  
Recurrence Risk ◽  
Disease Recurrence ◽  
Papillary Thyroid ◽  
Ww Domain ◽  
Normal Tissues

Objectives. Many patients with papillary thyroid cancer (PTC) have a high recurrence risk and poor prognosis, and the main obstacle to the clinical diagnosis and treatment of PTC is lack of effective predictive molecular markers. The purpose of this study was to investigate the clinicopathological and prognostic implications of WW domain binding protein 5 (WBP5) expression in PTC. Materials and Methods. Immunohistochemistry of WBP5 was performed using tissue microarrays of 131 patients with PTC who underwent surgery during January 2006 and January 2010 in the Zhejiang Cancer Hospital. Statistical analyses were conducted to evaluate the association between WBP5 expression and the clinicopathological features and to analyze the disease-free survival (DFS) and prognostic factors. Results and Conclusion. The positive expression rate of WBP5 in PTC and the adjacent normal tissues was 42.75% (56/131) and 45.45% (10/22), respectively. WBP5 expression was significantly correlated with bilaterality, capsule invasion, and N-stage, and it was a favorable factor of DFS. Moreover, patients with a high WBP5 expression exhibited reduced risk of disease recurrence compared with that in patients with low WBP5 expression in the univariate analysis, whereas the multivariate analysis suggested that WBP5 was not an independent prognostic factor. Our results indicate that WBP5 might be a favorable prognosis indicator of PTC.

scholarly journals Prognostic significance of mesothelin expression in colorectal cancer disclosed by area-specific four-point tissue microarrays

2020 ◽  
Vol 477 (3) ◽  
pp. 409-420
Author(s):  
Takehiro Shiraishi ◽  
Eiji Shinto ◽  
Ines P. Nearchou ◽  
Hitoshi Tsuda ◽  
Yoshiki Kajiwara ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Significance ◽  
Tissue Microarrays ◽  
Mesothelin Expression

scholarly journals Prognostic Significance of JMJD3 Expression in Pleural Mesotheliomas

2021 ◽  
Vol 2 (3) ◽  
pp. 223-232
Author(s):  
Lauren Rask-Nielsen ◽  
Sarita Prabhakaran ◽  
Ashleigh J. Hocking ◽  
Matthew Hussey ◽  
Sonja Klebe
Keyword(s):  
Asbestos Exposure ◽  
Treatment Options ◽  
Prognostic Significance ◽  
Survival Outcomes ◽  
Pleural Mesothelioma ◽  
Poor Survival ◽  
Cytoplasmic Expression ◽  
Variable Expression ◽  
Independent Prognostic Marker ◽  
Nuclear Expression

Pleural mesothelioma is a disease associated with asbestos exposure and patients often have poor prognosis. Biomarkers that can stratify tumours more efficiently are much sought after to enable more personalized treatment options and predict prognosis. Jumonji domain-containing protein D3 (JMJD3) has variable expression in a range of tumours. However, there has been much discordance in the immunohistochemical labelling of JMJD3 between cancers at different sites and ambiguity exists regarding its functional significance. Recent evidence suggests that although nuclear expression of JMJD3 has a demethylase role in most cancers, there are also demethylase-independent actions of JMJD3 that need to be explored including its cytoplasmic expression. We analysed JMJD3 labelling in 99 pleural mesothelioma tissues and correlated nuclear and cytoplasmic expression with survival outcomes. We found that low nuclear and high cytoplasmic expression were associated with poor survival outcomes in our cohort (p = 0.014 and p = 0.041, respectively). Additionally, we found that low nuclear expression of JMJD3 was frequent in the sarcomatoid subtype (p < 0.001). Finally, we showed that cytoplasmic labelling is an independent prognostic marker of poor survival. Our cohort only contained a small number of tumours with high cytoplasmic expression of JMJD3, and a larger cohort study may provide clearer stratification.

scholarly journals 3089 Clinicopathologic and Prognostic Significance of LGR5, a Cancer Stem cell Marker in Peritoneal Metastasis of a Colorectal Origin

2019 ◽  
Vol 3 (s1) ◽  
pp. 103-103
Author(s):  
Chukwuemeka Ihemelandu
Keyword(s):  
Colorectal Cancer ◽  
Stem Cell ◽  
Survival Analysis ◽  
Cancer Patients ◽  
Peritoneal Metastasis ◽  
Prognostic Significance ◽  
Stem Cell Marker ◽  
Normal Tissues ◽  
Lgr5 Expression ◽  
Colorectal Cancer Patients

OBJECTIVES/SPECIFIC AIMS: Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is expressed on Wnt/β-catenin-dependent adult stem cell populations of the colon. Cancer stem cells are hypothesized to be the driving force behind tumor progression and metastasis, making them attractive therapeutic targets. Our aim was to analyze the clinicopathologic and prognostic significance of LGR5 expression in a cohort of colorectal cancer patients with peritoneal metastasis. METHODS/STUDY POPULATION: A total of 49 Formalin-fixed paraffin-embedded (FFPE) tissue blocks of primary or metastatic tumors and their respective normal tissues were collected from the tissue bank for time period 2009-2015. LGR5 expression was assessed at the protein level through immunohistochemical (IHC) staining of tissue microarray (TMA) constructs consisting of pairs of tumor and normal colon tissue. The correlation between LGR5 expression and clinicopathologic parameters and prognosis was assessed by statistical analysis. RESULTS/ANTICIPATED RESULTS: Of the 49 patient sample, 30(61.22%) were female vs. 19 (38.78%) males. Age range at initial diagnosis ranged from 31.7 years to 84.4 years, with a median age of 61.29 years. Duration of follow-up ranged from 1 – 9 years with a median of 5 years.LGR5 expression was higher in colorectal cancer than in normal mucosa. In univariate survival analysis overexpression of LGR5 was significantly associated with improved survival (p=0.002).Of significance, LGR5 positivity was an independent prognostic marker for better prognosis in a multivariate survival analysis adjusting for prognostic variables age, stage, gender, tumor histology and grade (HR 2.67. 95% CI 1.01-7.00, P = 0.046). DISCUSSION/SIGNIFICANCE OF IMPACT: LGR5 was significantly over expressed in colorectal cancer compared to normal tissues. LGR5 was noted to be an independent prognostic variable for an improved survival outcome in colorectal cancer patients with peritoneal metastasis, making LGR5 a potential therapeutic target in colorectal cancer patients with peritoneal metastasis.

scholarly journals Network Pharmacology Interpretation of Fuzheng–Jiedu Decoction against Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-16 ◽  
Author(s):  
Hongshuo Shi ◽  
Sisheng Tian ◽  
Hu Tian
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Receptor ◽  
Point Of View ◽  
Network Pharmacology ◽  
Biological Processes ◽  
Kegg Pathways ◽  
Potential Target ◽  
Pathways Analysis

Introduction. Traditional Chinese medicine (TCM) believes that the pathogenic factors of colorectal cancer (CRC) are “deficiency, dampness, stasis, and toxin,” and Fuzheng–Jiedu Decoction (FJD) can resist these factors. In this study, we want to find out the potential targets and pathways of FJD in the treatment of CRC and also explain from a scientific point of view that FJD multidrug combination can resist “deficiency, dampness, stasis, and toxin.” Methods. We get the composition of FJD from the TCMSP database and get its potential target. We also get the potential target of colorectal cancer according to the OMIM Database, TTD Database, GeneCards Database, CTD Database, DrugBank Database, and DisGeNET Database. Subsequently, PPI analysis, KEGG pathways analysis, and GO biological processes analysis were carried out for the target of FJD in the therapy of colorectal cancer. In addition, we have also built a relevant network diagram. Results. In this study, we identified four core compounds of FJD in the therapy of colorectal cancer, including quercetin, kaempferol, beta-sitosterol, and stigmasterol. At the same time, we also obtained 30 core targets, including STAT3, INS, TP53, VEGFA, AKT1, TNF, IL6, JUN, EGF, CASP3, MAPK3, MAPK1, MAPK8, SRC, IGF1, CCND1, ESR1, EGFR, PTEN, MTOR, FOS, PTGS2, CXCL8, HRAS, CDH1, BCL2L1, FN1, MMP9, ERBB2, and JAK2. FJD treatment of colorectal cancer mainly involves 112 KEGG pathways, including FoxO (hsa04068) signaling pathway, PI3K-Akt (hsa04151) signaling pathway, HIF-1 (hsa04066) signaling pathway, T cell receptor (hsa04660) signaling pathway, and ErbB (hsa04012) signaling pathway. At the same time, 330 GO biological processes were summarized, including cell proliferation, cell apoptosis, angiogenesis, inflammation, and immune. Conclusions. In this study, we found that FJD can regulate cell proliferation, apoptosis, inflammation and immunity, and angiogenesis through PI3K-Akt signaling pathway to play an anti-CRC effect.

scholarly journals Identification of Hub Genes for Controlling Cancer Stem Cell Characteristics in Colorectal Cancer by Bioinformatics Analysis

2021 ◽  
Author(s):  
Xiang Li ◽  
Shuoyang Huang ◽  
Chao Yang ◽  
Yongbin Zheng
Keyword(s):  
Colorectal Cancer ◽  
Stem Cell ◽  
Survival Data ◽  
Prognostic Model ◽  
The Cancer Genome Atlas ◽  
Lasso Regression ◽  
Immune Microenvironment ◽  
Hub Genes ◽  
Normal Tissues ◽  
Cancer Genome Atlas

Abstract Background Cancer stem cells (CSCs), which are capable of infinite proliferation and self-renewal, play a crucial role in the occurrence and development of colorectal cancer (CRC). The study of the expression characteristics of CRC stem cell-related genes and their interaction with the immune microenvironment may contribute to CRC treatment. Results In order to explore the hub genes that regulate the stemness characteristics of CRC, we obtained gene expression values of the Cancer Genome Atlas (TCGA), stemness indices (mRNAsi), and corresponding survival data from UCSC Xena Browser. Differentially expressed genes (DEGs) were identified in cancer and normal tissues. Then we screened 2 modules and 210 mRNAsi-related genes from 4,941 DEGs by weighted gene co-expression network analysis. A prognostic model including ten genes (VCAN, SPARC, COL12A1, THBS2, COL1A2, COL5A1, TAGLN, DCN, MYH11, CDH11) was constructed using protein interaction networks and LASSO regression. We also evaluated the relationship between cancer stemness and immune response and found there was a strong correlation between each other. Conclusions Our study establishes a prognostic model associated with CSCs and reveals the association between mRNAsi and the tumor immune microenvironment, which is useful for the targeted therapy of CRC.

scholarly journals RGL2 Drives the Metastatic Progression of Colorectal Cancer via Preventing the Protein Degradation of β-catenin and KRAS

2021 ◽  
Author(s):  
Meng-Shun Sun ◽  
Lan-Ting Yuan ◽  
Chia-Hao Kuei ◽  
Hui-Yu Lin ◽  
Yen-Lin Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Degradation ◽  
Prognostic Significance ◽  
Metastatic Potential ◽  
Gene Set Enrichment Analysis ◽  
Cellular Migration ◽  
Metastatic Progression ◽  
Primary Tumors ◽  
Mesenchymal Transition ◽  
Normal Tissues

Abstract Background: Colorectal cancer (CRC) is a common cancer and results in high mortality worldwide, owing to cancer progression, e.g., metastasis. However, the molecular mechanism underlying the metastatic evolution of CRC remains largely unknown. In this study, we investigated the clinical relevance and oncogenic function of RGL2 in CRC.Methods: Cellular migration ability was assessed by transwell cultivation. The metastatic potential was estimated by lung colony-forming assay. DNA-binding activity of transcription factors was determined by luciferase-based reporter assay. RGL2 expression was analyzed by immunohistochemistry in human CRC specimens. RGL2 mRNA expression from the Cancer Genome Atlas (TCGA) CRC database was compared between the primary tumors and normal tissues.Results: The upregulation of Ral Guanine Nucleotide Dissociation Stimulator Like 2 (RGL2) was commonly detected in primary tumors compared with normal tissues and is significantly associated with a poorer prognosis in CRC patients. Moreover, RGL2 expression appeared to positively correlate with the metastatic potential of CRC cells. Whereas RGL2 knockdown dramatically suppressed the metastatic potential of CRC cells in vitro and in vivo, RGL2 overexpression in poorly metastatic CRC cells and reconstitution in RGL2-silenced CRC cells enhanced and rescued the cellular metastatic ability, respectively. Computational simulation using the Gene Set Enrichment Analysis program and cell-based assays demonstrated that RGL2 expression was causally associated with the activity of the Wnt/β-catenin signaling axis and KRAS, as well as the progression of epithelial-mesenchymal transition (EMT) in the detected CRC cells. Importantly, RGL2 upregulation was capable of preventing the protein degradation of β-catenin and KRAS in CRC cells. Conclusion: RGL2 has metastasis-promoting effects via stabilizing β-catenin and KRAS in CRC cells and prognostic significance in CRC patients. These findings suggest that RGL2 acts as a driver to promote the metastatic progression of CRC and serves as a poor prognostic biomarker in CRC patients.

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