scholarly journals Methylation Status of Corticotropin-Releasing Factor (CRF) Receptor Genes in Colorectal Cancer

2021 ◽  
Vol 10 (12) ◽  
pp. 2680
Author(s):  
Maria Panagopoulou ◽  
Antonia Cheretaki ◽  
Makrina Karaglani ◽  
Ioanna Balgkouranidou ◽  
Eirini Biziota ◽  
...  

The corticotropin-releasing factor (CRF) system has been strongly associated with gastrointestinal pathophysiology, including colorectal cancer (CRC). We previously showed that altered expression of CRF receptors (CRFRs) in the colon critically affects CRC progression and aggressiveness through regulation of colonic inflammation. Here, we aimed to assess the potential of CRFR methylation levels as putative biomarkers in CRC. In silico methylation analysis of CRF receptor 1 (CRFR1) and CRF receptor 2 (CRFR2) was performed using methylome data derived by CRC and Crohn’s disease (CD) tissues and CRC-derived circulating cell-free DNAs (ccfDNAs). In total, 32 and 33 differentially methylated sites of CpGs (DMCs) emerged in CRFR1 and CRFR2, respectively, between healthy and diseased tissues. The methylation patterns were verified in patient-derived ccfDNA samples by qMSP and associated with clinicopathological characteristics. An automated machine learning (AutoML) technology was applied to ccfDNA samples for classification analysis. In silico analysis revealed increased methylation of both CRFRs in CRC tissue and ccfDNA-derived datasets. CRFR1 hypermethylation was also noticed in gene body DMCs of CD patients. CRFR1 hypermethylation was further validated in CRC adjuvant-derived ccfDNA samples, whereas CRFR1 hypomethylation, observed in metastasis-derived ccfDNAs, was correlated to disease aggressiveness and adverse prognostic characteristics. AutoML analysis based on CRFRs methylation status revealed a three-feature high-performing biosignature for CRC diagnosis with an estimated AUC of 0.929. Monitoring of CRFRs methylation-based signature in CRC tissues and ccfDNAs may be of high diagnostic and prognostic significance in CRC.

2017 ◽  
Vol 152 (5) ◽  
pp. S1018
Author(s):  
Hiroyuki Takamaru ◽  
Yutaka Saito ◽  
Taku Sakamoto ◽  
Seiichiro Abe ◽  
Masayoshi Yamada ◽  
...  

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Athanasios Tampakis ◽  
Ekaterini-Christina Tampaki ◽  
Afrodite Nonni ◽  
Ioannis D. Kostakis ◽  
Alberto Posabella ◽  
...  

Abstract Background Fascin is the main actin cross-linker protein that regulates adhesion dynamics and stabilizes cell protrusion, such as filopodia. In human cancer, fascin expression correlates with aggressive clinical features. This study aimed to determine the expression patterns of fascin-1 and assessed its prognostic significance in colorectal cancer. Methods One hundred eleven specimens of patients with primary resectable colorectal cancer were examined via immunohistochemistry for the expression of fascin-1, and the results were correlated with clinicopathological characteristics and survival data. Results Fascin-1 staining displayed strong intensity in the cytoplasm of the colorectal cancer cells and endothelial cells of tumor blood vessels. Moderate to high fascin-1 expression was associated with progressive anatomic disease extent (p < 0.001), higher T classification (p = 0.007), the presence of lymph node (p < 0.001) and distant metastasis (p = 0.002), high grade tumors (p = 0.002) and vascular invasion (p < 0.001). Patients displaying moderate and high fascin-1 expression demonstrated a significantly worse 5-year overall survival [HR; 3.906, (95%CI) = 1.250–12.195] and significantly worse 3-year progression-free survival [HR; 3.448, (95%CI) = 1.401–8.475] independent of other clinicopathological characteristics. Besides, high fascin-1 expression in early-stage cancer only was associated with a dismal prognosis. Conclusions High fascin-1 expression in colorectal cancer is an independent negative prognostic factor for survival, increasing the risk for disease recurrence or death almost by sevenfold. Fascin-1 expression could be potentially utilized to identify high-risk patients prone to metastasis already in early-stage disease.


2020 ◽  
Vol 89 ◽  
pp. 107370
Author(s):  
Tayyebeh Ghasemi ◽  
Mohammad Khalaj-Kondori ◽  
Mohammad Ali Hosseinpour feizi ◽  
Parviz Asadi

2021 ◽  
Vol 22 (24) ◽  
pp. 13283
Author(s):  
Maria Radanova ◽  
Galya Mihaylova ◽  
Oskan Tasinov ◽  
Desislava P. Ivanova ◽  
George St. Stoyanov ◽  
...  

Circular RNAs (circRNAs) are a group of special endogenous long non-coding RNAs which are highly stable in the circulation, and, thus, more suitable as new biomarkers of colorectal cancer (CRC). The aim of our study was to explore the plasma expression levels of four circRNAs: has_circ_0001445, hsa_circ_0003028, hsa_circ_0007915 and hsa_circ_0008717 in patients with CRC and to evaluate their associations with clinicopathological characteristics and the clinical outcome of the patients. CircRNAs were extracted from patients’ plasma obtained prior to chemotherapy. Their expression levels were measured by qPCR and calculated applying the 2−ΔΔCt method. The levels of all four circRNAs were significantly increased in the plasma of CRC patients. At the optimal cut-off values hsa_circ_0001445 and hsa_circ_0007915 in plasma could significantly distinguish between patients with or without metastatic CRC with 92.56% sensitivity and 42.86% specificity, and with 86.07% sensitivity and 57.14% specificity, respectively. The mean overall survival (OS) of patients with high/intermediate expression of hsa_circ_0001445 was 30 months, significantly higher in comparison with the mean OS of the patients with low expression—20 months (log-rank test, p = 0.034). In multivariate Cox regression analysis, the low levels of hsa_circ_0001445 were also associated with shorter survival (HR = 1.59, 95% CI: 1.02–2.47, p = 0.040). A prognostic significance of hsa_circ_0001445 for patients with metastatic CRC was established.


2020 ◽  
Author(s):  
Athanasios Tampakis ◽  
Ekaterini Christina Tampaki ◽  
Afrodite Nonni ◽  
Ioannis D. Kostakis ◽  
Alberto Posabella ◽  
...  

Abstract Background; Fascin is the main actin cross-linker protein that regulates adhesion dynamics and stabilizes cell protrusion, such as filopodia. In human cancer, fascin expression correlates with aggressive clinical features. This study aimed to determine the expression patterns of fascin-1 and assess its prognostic significance in colorectal cancer. Methods; One hundred eleven specimens of patients with primary resectable colorectal cancer were examined via immunohistochemistry for the expression of fascin-1, and the results were correlated with clinicopathological characteristics and survival data. Results; Fascin-1 staining displayed strong intensity in the cytoplasm of the colorectal cancer cells and endothelial cells of tumor blood vessels. Moderate and high fascin-1 expression was associated with progressive anatomic disease extent (p < 0.001), higher T classification (p = 0.007), the presence of lymph node (p < 0.001) and distant metastasis (p = 0.002), high grade tumors (p = 0.002) and vascular invasion (p < 0.001). Patients displaying moderate and high fascin-1 expression demonstrated a significantly worse 5-year overall survival [HR; 3.906, (95%CI) = 1.250-12.195] and significantly worse 3-year progression-free survival [HR; 3.448, (95%CI) = 1.401–8.475] independent of other clinicopathological characteristics. Besides, high fascin-1 expression in early-stage cancer only was associated with a dismal prognosis. Conclusions; High fascin-1 expression in colorectal cancer is an independent negative prognostic factor for survival, increasing the risk for disease recurrence or death almost by sevenfold. Fascin-1 expression could be potentially utilized to identify high-risk patients prone to metastasis already in early-stage disease.


2020 ◽  
Vol 72 (1) ◽  
pp. 31-36
Author(s):  
Lidija Todorovic ◽  
Vesna Mandusic ◽  
Biljana Vucetic-Tadic ◽  
Vladan Zivaljevic ◽  
Ivan Paunovic ◽  
...  

A growing number of studies suggest a tumor suppressive role and potential prognostic significance of miR- 30a-3p in different types of cancer. However, relatively few studies have focused on this microRNA in neoplastic thyroid lesions, including papillary thyroid cancer (PTC). The aim of our study was to shed more light on the potential involvement and clinical relevance of miR-30a-3p in this type of cancer. We examined the expression levels of this microRNA in 42 pairs of PTCs and matched non-tumor thyroid tissues using quantitative RT-PCR. We analyzed their association with clinical and histopathological parameters. The results revealed that miR-30a-3p was significantly downregulated in the majority of PTC tissues compared to corresponding non-tumor tissues. Moreover, decreased expression of miR-30a-3p was associated with advanced clinical stage, presence of multiple tumor foci and capsular invasion, suggesting a role in aggressive disease. Although the role of this microRNA and its prognostic utility remain to be elucidated, the presented data suggest that downregulated expression of miR-30a-3p indicates poorer prognosis in PTC patients, warranting further investigations.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ryuk Jun Kwon ◽  
Eun-Ju Park ◽  
Sang Yeoup Lee ◽  
Youngin Lee ◽  
Chungsu Hwang ◽  
...  

Abstract Background Colorectal cancer (CRC) is a malignancy of the large intestine, whose development and prognosis have been demonstrated to be associated with altered lipid metabolism. High cholesterol intake is associated with an increased risk of CRC, and elevated serum cholesterol levels are known to be correlated with risk of developing CRC. Niemann-Pick C1-Like 1 (NPC1L1), a target of ezetimibe, plays an essential role in the absorption of intestinal cholesterol. However, whether the altered expression of NPC1L1 affects CRC development and prognosis is currently unknown. Methods Data corresponding to patients with CRC were obtained from The Cancer Genome Atlas (TCAG). Datasets from the Genome Data Analysis Center (GDAC) platform were analyzed to compare the expression of NPC1L1 in normal and CRC tissues using the Mann–Whitney U test and chi-square test. Further, the datasets from the Gene Expression Omnibus (GEO) database were analyzed. The log-rank test and multivariate Cox proportional hazard regression analysis were performed to determine whether NPC1L1 significantly affects the prognosis of CRC. Results The expression of NPC1L1 was found to be upregulated in CRC and was significantly associated with the N and pathological stages but not with the histological type, age, and sex. Increased NPC1L1 expression in CRC was related to poor patient survival, as evidenced by the Kaplan–Meier and multivariate regression analyses. Conclusions As high expression of NPC1L1 was associated with CRC development, pathological stage, and prognosis, NPC1L1 can serve as an independent prognostic marker for CRC.


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