Prognosis In Colorectal Carcinoma Patients Research Articles

Lectin-Based Immunophenotyping and Whole Proteomic Profiling of CT-26 Colon Carcinoma Murine Model.

A murine colorectal carcinoma (CRC) model was established. CT26 colon carcinoma cells were injected into BALB/c mice's spleen to study the primary tumor and the mechanisms of cell spread of colon cancer to the liver. The CRC was verified by the immunohistochemistry of Pan Cytokeratin and Vimentin expression. Immunophenotyping of leukocytes isolated from CRC-bearing BALB/c mice or healthy controls, such as CD19+ B cells, CD11+ myeloid cells, and CD3+ T cells, was carried out using fluorochrome-labeled lectins. The binding of six lectins to white blood cells, such as galectin-1 (Gal1), siglec-1 (Sig1), Sambucus nigra lectin (SNA), Aleuria aurantia lectin (AAL), Phytolacca americana lectin (PWM), and galectin-3 (Gal3), was assayed. Flow cytometric analysis of the splenocytes revealed the increased binding of SNA, and AAL to CD3 + T cells and CD11b myeloid cells; and increased siglec-1 and AAL binding to CD19 B cells of the tumor-bearing mice. The whole proteomic analysis of the established CRC-bearing liver and spleen versus healthy tissues identified differentially expressed proteins, characteristic of the primary or secondary CRC tissues. KEGG Gene Ontology bioinformatic analysis delineated the established murine CRC characteristic protein interaction networks, biological pathways, and cellular processes involved in CRC. Galectin-1 and S100A4 were identified as upregulated proteins in the primary and secondary CT26 tumor tissues, and these were previously reported to contribute to the poor prognosis of CRC patients. Modelling the development of liver colonization of CRC by the injection of CT26 cells into the spleen may facilitate the understanding of carcinogenesis in human CRC and contribute to the development of novel therapeutic strategies.

Prognostic Clinicopathological Parameters in Colorectal Carcinoma

Background: Colorectal carcinoma (CRC) is the third cause of cancer-related death worldwide Methods: This study aimed to assess the clinicopathological parameters and their correlation with prognosis in patients with colorectal carcinoma. Two hundred pathology reports for cases diagnosed with CRC in Doctor Soliman Fakeeh Hospital (DSFH) in the period 2000 to 2023 were retrieved from the archives and the Yasashi database of Fakeeh Hospital for reviewing the clinical and pathological data. Univariate & multivariate analyses were conducted. Results: A total of 50 reports were included in the study. In regard to the relation between clinicopathological findings and the prognosis of CRC, there was a statistically significant relation between grade of the tumor and its metastasis (p-value = 0.024). However, there was a statistically insignificant relationship to gender, age, diabetes mellitus status, neoadjuvant chemotherapy, surgical operation, location of the tumor, and invasion of the surrounding tissues. Conclusion: The study highlighted the significant correlation between clinicopathological findings, particularly the grade of the tumor, and the prognosis of colorectal carcinoma. Factors like tumor size, metastasis, and histological grade played crucial roles in determining the prognosis of CRC patients.

Evaluation of HHLA2 and CD8 Immunohistochemical Expression in Colorectal Carcinoma and Their Prognostic Significance.

Colorectal carcinoma (CRC) is the third most common malignancy worldwide. Human endogenous retrovirus H long terminal repeat-associating protein 2 (HHLA2) is a novel immune checkpoint molecule. The association between HHLA2 expression and clinicopathological features and its prognostic significance in CRC patients are still controversial. The aim of this study is to evaluate the prognostic value of immunohistochemical (IHC) expression of HHLA2 and CD8 in CRC. This retrospective study included 134 cases diagnosed with primary CRC at the Gastrointestinal Surgery Center (GISC) department, Mansoura Faculty of Medicine, during the period from December 2014 to December 2018. Clinicopathological and survival data were collected. IHC for HHLA2 and CD8 was performed, and they were correlated with clinicopathological parameters and patient prognosis. Among 134 CRC cases, high HHLA2 expression was detected in 73 (54.5%). High HHLA2 expression was significantly related to the depth of invasion (P = 0.005*), lymph node metastasis (P = 0.01*), tumor stage )P = 0.002*), and distant recurrence )P = 0.012*). Multivariate analysis spotted HHLA2 high expression as an independent prognostic predictor for OS in CRC (P = 0.03*) and DFS (P = 0.008*). CD8 shows a significant correlation with tumor infiltrating lymphocytes (TILs) (P ≤ 0.001*), absence of metastasis ((P = 0.029*), absence of tumor deposits (P=0.014*). However, CD8 shows no significant association with survival or HHLA2. HHLA2 is an independent prognostic factor for the overall survival and disease free survival of CRC patients and can predict poor prognosis in CRC patients.

HOXD9 Stimulates the Process of Colorectal Carcinoma by Regulating KLK9

Colorectal carcinoma (CRC) is a common tumor in the digestive system. This study aims to elucidate the possible relationship between abnormally expressed HOXD9 and the malignant process of CRC. HOXD9 levels were analyzed in CRC and adjacent non-tumoral tissues to evaluate its prognostic value in CRC patients. Knockdown of HOXD9 was performed, and the proliferative and migratory capacities of LoVo and LS513 cells were assessed using CCK-8, transwell, and wound healing assays. Bioinformatic analysis and dual-luciferase reporter assay revealed the interaction between HOXD9 and KLK9. Rescue experiments were conducted to elucidate the co-regulation of HOXD9 and KLK9 on CRC cell behaviors. HOXD9 was upregulated in CRC tissues, and high level of HOXD9 predicted poor prognosis in CRC patients. HOXD9 was identically upregulated in CRC cell lines, especially LoVo and LS513 cells, which were used for generating HOXD9 knockdown models by transfection of sh-HOXD9. Knockdown of HOXD9 weakened proliferative and migratory capacities in CRC cells. KLK9 was the target binding HOXD9, which was downregulated in CRC tissues and cell lines. Knockdown of KLK9 reversed the inhibited proliferative and migratory capacities in CRC cells owing to HOXD9 knockdown. Highly expressed HOXD9 in CRC tissues is closely linked to the prognosis. HOXD9 stimulates CRC cells to proliferate and migrate by upregulating KLK9.

Cancer-Associated Fibroblast Risk Model for Prediction of Colorectal Carcinoma Prognosis and Therapeutic Responses.

Colorectal carcinoma (CRC) is a malignant tumor of the digestive system. Cancer-associated fibroblasts (CAFs) are important cellular elements in the tumor microenvironment of CRC, which contribute to CRC progression and immune escape. To predict the survival outcome and therapeutic responses of CRC patients, we identified genes connected with stromal CAF and generated a risk model. In this study, we used multiple algorithms to reveal CAF-related genes in the Gene Expression Omnibus and The Cancer Genome Atlas datasets and construct a risk model composed by prognostic CAF-associated genes. Then, we evaluated whether the risk score could predict CAF infiltrations and immunotherapy in CRC and confirmed the expression of the risk model in CAFs. Our results showed that CRC patients with high CAF infiltrations and stromal score had worse prognosis than those with low-CAF infiltrations and stromal score. We obtained 88 stromal CAF-associated hub-genes and generated a CAF risk model consisting of ZNF532 and COLEC12. Compared with low-risk group, the overall survival in high-risk group was shorter. The relationship between risk score, ZNF532 and COLEC12, and stromal CAF infiltrations and CAF markers was positive. In addition, the effect of immunotherapy in the high-risk group was not as good as that in the low-risk group. Patients with the high-risk group were enriched in chemokine signaling pathway, cytokine-cytokine receptor interaction, and focal adhesion. Finally, we confirmed that the expressions of ZNF532 and COLEC12 in risk model were widely distributed in fibroblasts of CRC, and the expression levels were higher in fibroblasts than CRC cells. In conclusion, the prognostic CAF signature of ZNF532 and COLEC12 can be applied not only to predict the prognosis of CRC patients but also to evaluate the immunotherapy response in CRC patients, and these findings provide the possibility for further development of individualized treatment for CRC.

Current Understanding of the Role of the Quadruplets in Colorectal Cancer Biology – Osteoprotegerin and its Ligands RANK/RANKL/TRAIL

Colorectal carcinoma (CRC) is one of the most prevalent forms of malignant tumors worldwide, with over 600,000 CRC-related deaths occurring annually. Despite major advances in surgical techniques and equipment, chemotherapy and radiation therapy, the prognosis for CRC patients remains poor because of distant metastasis and recurrence. Traditionally, the identification of patients at high risk of recurrence or distant metastasis has depended on pathological characteristics, such as depth of invasion, nodal metastasis, stage group and perforation or invasion of adjacent organs. However, the current tumor-node-metastasis (TNM) classification system is limited in that it cannot offer a prognosis for individual patients. To improve the outcome of patients with CRC, it is crucial to identify cancer-related genes that can serve as predictive and prognostic biomarkers to individualize therapy. Osteoprotegerin (OPG) is a member of the tumor necrosis factor (TNF) receptor superfamily. It has been shown that OPG is involved in the development and progression of human malignancies. This review summarizes our current understanding of the role of OPG in fibrosis and will discuss its potential as a biomarker and/or novel therapeutic target for fibrosis.&nbsp

Landscape of DNA damage response gene mutations in microsatellite-stable colorectal carcinoma.

e15558 Background: Colorectal carcinoma (CRC) is one of the most frequent and lethal cancers in the world. Important therapeutic progress of immune checkpoint inhibitors (ICIs) is limited to molecular niche of CRC with microsatellite-stable(MSS). The identification of genomic alterations in the DNA damage response (DDR) pathway have been recognized as pathogenic factors in hereditary cancer predisposition. Few studies showed the effects of ICIs on DDR pathway in patients with MSS CRC. Some reports suggested that DDR could reshape tumor immune microenvironment by regulating tissue repair and local immune response. Here we evaluated the molecular roles of DDR pathway and the immune microenvironment in efficacy of immunotherapy in MSS CRC. Methods: A total of 67 patients with MSS CRC were enrolled into the study. All samples were collected and detected by using NGS with a 1021 gene panel which containing 56 DDR genes (Supplementary table 1). Furthermore, comprehensive bioinformatics analysis were performed by the TCGA and MSK data. We defined pathway alteration as at least one gene in DDR pathway mutated. Results: In our results, three DDR pathway alteration showed poor prognosis (P = 0.0167) compared with DDR wild type in TCGA data (Figure 1A). The MSK data demonstrated that three DDR pathway alteration were associated with a better prognosis in MSS CRC patients through ICIs therapy (P = 0.0416, P = 0.00627, respectively, Figure 1B). The clinical data suggested the patient with DDR pathway alteration had longer OS (354.7 ± 134.0 days, PR) than the others with DDR wild type (247.1± 258.4 days, PD/SD) after PD-1-targeted therapies (P = 1.587e-08). Moreover, the patient with DDR pathway alteration showed significant longer PFS (312.3 ± 179.2 days, PR) compared with DDR wild type (163.3 ± 157.7 days, PD/SD) through immune therapies (P = 4.249e-10). Moreover, significant results of immune infiltrate deconvolution revealed resting memory CD4+ T cells were the most prevalent population between DDR pathway alteration and DDR wild type using CIBERSORT analysis (P = 0.0295, Figure 1C). The activated memory CD4+ T cells in DDR pathway alteration were lower than DDR wild type (P = 0.00858, Figure 1C-D) in patients with MSS CRC. The effects of DDR pathway alteration on immune microenvironment was also necessary for effective PD-1-targeted therapy in future study. Our results suggest that two or more DDR pathways and CD4 + T cells may serve as immunotherapy markers for advanced MSS colorectal cancer. Conclusions: Mutations in DDR pathway may serve as a biomarker for PD-1-targeted therapy through memory CD4+ T cells for MSS CRC patients, which warrants further studies.

KLF16 enhances stress tolerance of colorectal carcinomas by modulating nucleolar homeostasis and translational reprogramming

Translational reprogramming is part of the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress, which acts to the advantage of cancer growth and development in different stress conditions, but the mechanism of ER stress-related translational reprogramming in colorectal carcinoma (CRC) progression remains unclear. Here, we identified that Krüppel-like factor 16 (KLF16) can promote CRC progression and stress tolerance through translational reprogramming. The expression of KLF16 was upregulated in CRC tissues and associated with poor prognosis for CRC patients. We found that ER stress inducers can recruit KLF16 to the nucleolus and increase its interaction with two essential proteins for nucleolar homeostasis: nucleophosmin1 (NPM1) and fibrillarin (FBL). Moreover, knockdown of KLF16 can dysregulate nucleolar homeostasis in CRC cells. Translation-reporter system and polysome profiling assays further showed that KLF16 can effectively promote cap-independent translation of ATF4, which can enhance ER-phagy and the proliferation of CRC cells. Overall, our study unveils a previously unrecognized role for KLF16 as an ER stress regulator through mediating translational reprogramming to enhance the stress tolerance of CRC cells and provides a potential therapeutic vulnerability.

N6-methyladenosine methyltransferase KIAA1429 elevates colorectal cancer aerobic glycolysis via HK2-dependent manner

ABSTRACT Emerging evidence has emphasized the critical roles played by N6-methyladenosine RNA (m6A) modification in colorectal carcinoma (CRC) initiation and progression. However, the roles and mechanism of m6A and KIAA1429 in CRC progression require further clarification. Here, our research aimed to investigate the functions of KIAA1429 in CRC tumorigenesis. Results indicated that KIAA1429 up-regulation closely correlated to the poor prognosis of CRC patients. Bio-functional assays demonstrated that KIAA1429 promoted the aerobic glycolysis, including glucose uptake, lactate production, ATP generation and extracellular acidification rate (ECAR). Mechanistically, KIAA1429 positively up-regulated HK2 level via increasing its mRNA stability by binding the m6A site of HK2 mRNA via m6A-independent manner. Collectively, our work indicates that KIAA1429 has the potential to promote CRC carcinogenesis by targeting HK2 via m6A-independent manner, providing insight into the critical roles of m6A in CRC.

TBX20 inhibits colorectal cancer tumorigenesis by impairing NHEJ-mediated DNA repair.

DNA high methylation is one of driving force for colorectal carcinoma (CRC) pathogenesis. Transcription factors (TFs) can determine cell fate and play fundamental roles in multistep process of tumorigenesis. Dysregulation of DNA methylation of TFs should be vital for the progression of CRC. Here, we demonstrated that TBX20, a T‐box TF family protein, was downregulated with hypermethylation of promoter in early‐stage CRC tissues and correlated with a poor prognosis for CRC patients. Moreover, we identified PDZRN3 as the E3 ubiquitin ligase of TBX20 protein, which mediated the ubiquitination and degradation of TBX20. Furthermore, we revealed that TBX20 suppressed cell proliferation and tumor growth through impairing non‐homologous DNA end joining (NHEJ)‐mediated double‐stranded break repair by binding the middle domain of both Ku70 and Ku80 and therefore inhibiting their recruitment on chromatin in CRC cells. Altogether, our results reveal the tumor‐suppressive role of TBX20 by inhibiting NHEJ‐mediated DNA repair in CRC cells, and provide a potential biomarker for predicting the prognosis of patients with early‐stage CRC and a therapeutic target for combination therapy.

Prognostic value of YKL-40 in colorectal carcinoma patients: A meta-analysis.

BACKGROUNDIn recent years, the predictive role of YKL-40 for long-term survival in colorectal cancer patients has been gradually investigated. However, whether it is a reliable and valuable prognostic indicator for patients with colorectal carcinoma has not been verified. AIMTo identify the prognostic value of serum/plasma concentration of YKL-40 or expression status of YKL-40 in tumor cells in colorectal carcinoma patients. METHODSSeveral electronic databases including the PubMed, EMBASE, Web of Science, CNKI, VIP and WanFang were searched for relevant studies. The hazard ratios (HR) and 95% confidence intervals (CI) were combined and the primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS), respectively. All statistical analysis were conducted by STATA 15.0 software. RESULTSA total of nine studies involving 2545 patients were included. The pooled results indicated that YKL-40 was significantly associated with poor OS (HR = 1.80, 95%CI: 1.32-2.45, P < 0.001) and PFS (HR = 1.62, 95%CI: 1.22-2.16, P = 0.001). Subgroup analysis stratified by the treatment, tumor type and source of YKL-40 showed similar results.CONCLUSIONElevated serum/plasma concentration of YKL-40 or positive expression in tumor cells was related with worse prognosis of colorectal carcinoma patients. YKL-40 might serve as a novel and reliable indicator for the evaluation of prognosis in colorectal cancer.

The Association of Programmed Death-Ligand 1 Expression with Clinicopathological Features, Lymph Node Metastasis and Survival Prognosis in Patients with Colorectal Carcinoma

Colorectal carcinoma (CRC) is one of the most frequently encountered neoplasms with high morbidity and mortality. Activation of the programmed death protein 1/ programmed death ligand 1 (PD-1/PD-L1) pathway results in tumor immune evasion by suppressing the activity of T cells. The correlation of PD-L1 with clinicopathological features, lymph node metastasis and prognosis is less clear. The aim of present work was to study the relationship between PD-L1 and clinicopathological features and prognosis of CRC patients. Three hundred and eighty-six patients were included in this study. Serum PD-L1 was measured by ELISA, and PD-L1 on tumor cells was evaluated by immunohistochemistry. Pretreatment levels of PD-L1 were significantly elevated in CRC patient sera compared to healthy donors (P<0.001). The mean value of PD-L1 in healthy donors, CRC with non-lymph node metastasis, and CRC with lymph node metastasis were 229.22±54.7pg/mL, 400.77±66.3pg/ mL, and 414.29±59.1pg/mL, respectively. The positive rate of PD-L1 in metastatic lymph node was higher than in primary tumor (P<0.001). PD-L1 negative patients had higher five-year survival rate than PD-L1 positive patients (68.57% vs 46.98%, P=0.012). The univariate analysis indicated that tumor differentiation, lymph node metastasis, and PD-L1 were correlated with five-year survival rate of CRC patients (all P < 0.018). Multivariate analysis showed that lymph node metastasis and PD-L1 were independent prognostic factors (all P < 0.008). Our study demonstrates that PD-L1 negative patients have better five-year survival rate, and PD-L1 and lymph node metastasis are independent prognostic factors in CRC patients.

Identifying GNG4 might play an important role in colorectal cancer TMB.

Colorectal carcinoma (CRC) is one of the most leading cause of cancer death all over the world. The tumor immune microenvironment is illustrated to be necessary for the progress of CRC. And the accumulating evidence indicated that tumor mutation burden (TMB) is effective in differentiating responding population of immune checkpoint inhibitor (ICI) therapies in various cancers. In this study, we aimed to evaluated the potential relationship between TMB and the recurrence risk of CRC. The transcriptomic and clinical data of CRC patients were collected from The Cancer Genome Atlas (TCGA) database (n= 382). Then the genomic analysis of tumor mutation burden and tumor purity were conducted by a computational method based on transcriptomic data. Firstly, we accessed the distribution of TMB and preferences at the gene and mutation level using somatic mutation data from TCGA data about CRC. We identified that high TMB predicted better prognosis of CRC patients. Secondly, the differentially expressed genes (DEGs) between the low TMB and high TMB group was clarified. Then the protein-protein interaction (PPI) analysis was performed, and the results confirmed ten hub genes among the DEGs. Utilizing the GEPIA web-tool, we discovered that GNG4 was up-regulated in tumor tissues, and GNG4 was related to the overall survival (OS) and tumor free survival (TFS) of CRC patients. Therefore, we considered GNG4 was essential for the tumor immune microenvironment of CRC. Furthermore, we also accessed the protein level of GNG4 in CRC and liver metastases from CRC. In this study, GNG4 was demonstrated to be the key element of the CRC TMB, which will be essential for the ICI therapy of CRC. Besides, GNG4 was up-regulated in CRC and liver metastases from CRC tissues. Thus, we thought that GNG4 might play an important role in colorectal cancer TMB and induce its metastasis in liver.

PPIP5K2 promotes colorectal carcinoma pathogenesis through facilitating DNA homologous recombination repair.

Colorectal carcinoma (CRC) is the second most deadly cancer worldwide. Therapies that take advantage of DNA repair defects have been explored in various tumors but not yet systematically in CRC. Here, we found that Diphosphoinositol Pentakisphosphate Kinase 2 (PPIP5K2), an inositol pyrophosphate kinase, was highly expressed in CRC and associated with a poor prognosis of CRC patients. In vitro and in vivo functional studies demonstrated that PPIP5K2 could promote the proliferation and migration ability of CRC cells independent of its inositol pyrophosphate kinase activity. Mechanically, S1006 dephosphorylation of PPIP5K2 could accelerate its dissociation with 14-3-3 in the cytoplasm, resulting in more nuclear distribution. Moreover, DNA damage treatments such as doxorubicin (DOX) or irradiation (IR) could induce nuclear translocation of PPIP5K2, which subsequently promoted homologous recombination (HR) repair by binding and recruiting RPA70 to the DNA damage site as a novel scaffold protein. Importantly, we verified that S1006 dephosphorylation of PPIP5K2 could significantly enhance the DNA repair ability of CRC cells through a series of DNA repair phenotype assays. In conclusion, PPIP5K2 is critical for enhancing the survival of CRC cells via facilitating DNA HR repair. Our findings revealed an unrecognized biological function and mechanism model of PPIP5K2 dependent on S1006 phosphorylation and provided a potential therapeutic target for CRC patients.

The Prognostic Significance of Hsp70 in Patients with Colorectal Cancer Patients: A PRISMA-Compliant Meta-Analysis.

Background Hsp70 (heat shock protein 70) plays a key role in carcinogenesis and cancer progression. However, the relationship between the Hsp70 expression level and the colorectal cancer patient survival is unknown. This study is aimed at investigating the relationship between Hsp70 and the prognosis of colorectal carcinoma patients. Methods PubMed, Web of Science, and Embase were used for systematic computer literature retrieval. Stata SE14.0 software was used for quantitative meta-analysis. Besides, data was extracted from selected articles. Relationships between Hsp70 expression level and prognosis were further studied. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were also computed. Results A total of 11 potentially eligible studies with 2269 patients were identified in 10 tumors from PubMed, Web of Science, and Embase. Hsp70 overexpression was associated with poor overall survival (OS) and disease-free survival (DFS) in colorectal carcinoma patients (HRs, 0.65 (95% CI: 0.52-0.78) and 0.77 (95% CI: 0.23-1.32), respectively). Conclusions Hsp70 overexpression can predict poor survival in colorectal cancer patients.

Loss of expression of Syndecan-1 is associated with Tumor Recurrence, Metastatic Potential, and Poor Survival in patients with Colorectal carcinoma.

Objective:The loss of expression of syndecansyndecan-1 is associated with poor prognosis in many types of human cancer. The objective of this study was to evaluate the relation between syndecan-1 immunoexpression and several clinicopathological parameters in a subset of colorectal carcinoma (CRC) patients.Methods:Pathology tissue blocks of 202 primary tumors, 41 adenomas, and 37 normal colonic mucosae were used in this study. The cases diagnosed in the period 1995–2015 was included in the study. Immunohistochemistry analysis was performed using anti-CD138/syndecan-1 (B-A38) mouse monoclonal antibody. A semiquantitative method was used to score the syndecan-1 expression based on an evaluation of the percentage and intensity of the membranous and cytoplasmic expression. The data collected from Pathology Department at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. This is a retrospective cohort study that was conducted from July 2018 until August 2019.Results:Loss of syndecan-1 immunoexpression was observed in 72 (42.6%), 5 (12.2%), and 3 (8.1%) cases of CRC, adenomas, and normal mucosae, respectively. Low expression of syndecan-1 showed an association with nodal (p=0.003) and distant (p=0.001) metastasis, lymphovascular invasion (p=0.001), and tumor recurrence (p=0.006). Low syndecan-1 expression were associated with short overall survival (OS) (log rank 4.019, p=0.045) and disease-free survival (DFS) probabilities (log rank 4.748, p=0.029).Conclusion:Loss of syndecan-1 immunoexpression is associated with metastatic potential, tumor recurrence and shorter survival in CRC and is considered a potential biomarker of poor prognosis in CRC patients.

Clinical value and potential association of Rab1A and FoxM1 aberrant expression in colorectal cancer

Colorectal carcinoma (CRC) is one of the most common malignancies with a dismal 5-year survival rate. Our recent study indicated that Rab1A expression was closely related to GLI1 expression. A previous study shows that aberrant overexpression of GLI1 promotes colorectal cancer metastasis via FoxM1 overexpression. However, the potential correlation between Rab1A and FoxM1 in CRC remains elusive. Immunohistochemistry was performed to investigate the association of the expression of Rab1A and FoxM1 and to determine the prognosis in 135 CRC tissue and adjacent normal tissues. Using Oncomine datasets, we found that Rab1A and FoxM1 mRNA were obviously upregulated in CRC tissues compared to normal tissues. Additionally, the expression of Rab1A and FoxM1 was significantly higher in CRC tissues than that in normal tissues. Rab1A expression was positively correlated with FoxM1 expression in CRC, especially in TNM stage III. In addition, Rab1A and FoxM1 overexpression was found to be significantly correlated with poor prognosis in CRC patients. Besides, both high expression of Rab1A and FoxM1 led to a worse prognosis than anyone low group, and both low expression of Rab1A and FoxM1 had a better prognosis than the anyone low group. Therefore, Rab1A and FoxM1 play crucial roles and could be used as clinical biomarkers in CRC.

Silence of ATAD2 inhibits proliferation of colorectal carcinoma via the Rb-E2F1 signaling.

This study aims to clarify the potential function of ATAD2 (ATPase family, AAA domain containing 2) in regulating proliferative and apoptotic abilities of colorectal carcinoma (CRC). ATAD2 levels in CRC specimens and cell lines were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Overall survival in CRC patients with high or low level of ATAD2 was assessed by Kaplan-Meier method. The correlation between ATAD2 level and clinical characteristics of CRC patients was analyzed by χ2 test. Univariable and multivariable Cox regression models were generated to illustrate potential risk factors for the overall survival of CRC. After knockdown of ATAD2 in SW620 cells, relative levels of Cyclin D1, ppRb, pRb, E2F1, Cyclin E and cleaved Caspase 3 were detected by Western blot. Regulatory effects of ATAD2 on viability, clonality, cell cycle distribution, and apoptosis in SW620 and HCT15 cells were examined by a series of functional experiments. Upregulated ATAD2 in CRC was correlated to tumor size, tumor node metastasis (TNM) staging, and histological classification of CRC. High level of ATAD2 predicted poor prognosis in CRC patients. Cox regression test suggested that ATAD2 level, tumor size, TNM staging and histological classification were independent factors influencing overall survival in CRC. Knockdown of ATAD2 reduced viability and clonality in SW620 and HCT15 cells. In addition, cell cycle was arrested in G1 phase and apoptosis was stimulated in CRC cells with ATAD2 knockdown. In SW620 cells transfected with ATAD2 shRNA, protein levels of Cyclin D1, ppRb, E2F1 and Cyclin E were downregulated, and cleaved Caspase 3 was upregulated. ATAD2 is upregulated in CRC tissues and correlated to poor prognosis of CRC patients. It exerts an anti-proliferation role in CRC by arresting cell cycle in G1/S phase and triggering apoptosis via the Rb-E2F1 signaling.

Monoamine Oxidase B Expression Correlates with a Poor Prognosis in Colorectal Cancer Patients and Is Significantly Associated with Epithelial-to-Mesenchymal Transition-Related Gene Signatures.

Monoamine oxidases (MAOs) including MAOA and MAOB are enzymes located on the outer membranes of mitochondria, which are responsible for catalyzing monoamine oxidation. Recently, increased level of MAOs were shown in several cancer types. However, possible roles of MAOs have not yet been elucidated in the progression and prognosis of colorectal carcinoma (CRC). We therefore analyzed the importance of MAOs in CRC by an in silico analysis and tissue microarrays. Several independent cohorts indicated that high expression of MAOB, but not MAOA, was correlated with a worse disease stage and poorer survival. In total, 203 colorectal adenocarcinoma cases underwent immunohistochemical staining of MAOs, and associations with clinicopathological parameters and patient outcomes were evaluated. We found that MAOB is highly expressed in CRC tissues compared to normal colorectal tissues, and its expression was significantly correlated with a higher recurrence rate and a poor prognosis. Moreover, according to the univariate and multivariate analyses, we found that MAOB could be an independent prognostic factor for overall survival and disease-free survival, and its prognostic value was better than T and N stage. Furthermore, significant positive and negative correlations of MAOB with mesenchymal-type and epithelial-type gene expressions were observed in CRC tissues. According to the highlighted characteristics of MAOB in CRC, MAOB can be used as a novel indicator to predict the progression and prognosis of CRC patients.

MicroRNA-95-3p inhibits cell proliferation and metastasis in colorectal carcinoma by HDGF

BackgroundMicroRNAs (miRNAs) play an important regulatory role in carcinogenesis and cancer progression. MiR-95-3p has been reported to be an oncogene in hepatocellular carcinoma. However, the role of miR-95-3p in colorectal carcinoma (CRC) remains unclear. MethodsmiR-95-3p was validated in an independent validation sample cohort of 215 CRC tissues. Functional assays, Cell proliferation (MTT) assay colony formation, wound healing, transwell and animal xenograft assays were used to determine the oppressor role of miR-95-3p in human CRC progression. Furthermore, Bioinformatics analysis, western blotting and dual-luciferase reporter assay were used to determine the mechanism by which miR-95-3p suppresses progression of CRC cells. ResultsIn this study, we found that miR-95-3p was downregulated in CRC tissues. The low level of miR-95-3p in CRC tumors was correlated with aggressive clinicopathological characteristics, and it predicted poor prognosis in CRC patients. The overexpression of miR-95-3p significantly inhibited CRC cell proliferation, colony formation and metastasis in vitro and in vivo. Bioinformatic analysis further identified hepatoma-derived growth factor (HDGF) as a novel target of miR-95-3p in CRC cells. These findings suggest that miR-95-3p regulates CRC cell survival, partially through the downregulation of HDGF. ConclusionsTherefore, the miR-95-3p/HDGF axis might serve as a novel therapeutic target in patients with CRC.