scholarly journals Absence of Autophagy-Related Proteins Expression Is Associated with Poor Prognosis in Patients with Colorectal Adenocarcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Ji Hye Choi ◽  
Young-Seok Cho ◽  
Yoon Ho Ko ◽  
Soon Uk Hong ◽  
Jin Hee Park ◽  
...  

Background/Aim.Autophagy, a cellular degradation process, has paradoxical roles in tumorigenesis and the progression of human cancers. The aim of this study was to investigate the expression levels of autophagy-related proteins in colorectal cancer (CRC) and to evaluate their prognostic significance.Methods.This study is a retrospective review of immunohistochemical and clinicopathological data. All specimens evaluated were obtained from 263 patients with colorectal cancer who had undergone surgery between November 1996 and August 2007. The primary outcomes measured were the expression levels of three autophagy-related proteins (ATG5, BECN1/Beclin 1, and Microtubule-associated protein 1 light chain 3B (LC3B)) by immunohistochemistry and its association in clinicopathological parameters and patient survival.Results.The autophagy-related protein expression frequencies were 65.1% (151/232) for ATG5, 71.3% (174/244) for BECN1, and 74.7% (186/249) for LC3B for the 263 patients. Correlation between the expression of autophagy-related proteins was significant for all protein pairs. Multivariate analysis showed that negative LC3B expression and absence of autophagy-related proteins expression were independently associated with poor prognosis.Conclusion.Absence of autophagy-related proteins expression is associated with poor clinical outcome in CRC, suggesting that these proteins have potential uses as novel prognostic markers.

Chemotherapy ◽  
2022 ◽  
pp. 1-10
Author(s):  
Cheng Yang ◽  
Na Xie ◽  
Zhifei Luo ◽  
Xiling Ruan ◽  
Yixin Zhang ◽  
...  

<b><i>Introduction:</i></b> We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC). <b><i>Methods:</i></b> CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry. <b><i>Results:</i></b> Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time. <b><i>Conclusion:</i></b> CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15086-e15086
Author(s):  
A. E. Kottorou ◽  
A. G. Antonacopoulou ◽  
L. Skarlas ◽  
P. D. Grivas ◽  
C. D. Scopa ◽  
...  

e15086 Background: Nuclear factor Y- C (NFY-C) gene encodes one of the three subunits of nuclear factor Y, a highly conserved transcription factor which binds to the promoters of a variety of genes, which are implicated in cell cycle progression, drug metabolism and antigen presentation. The purpose of the current study was to investigate the role of NFY-C in colorectal cancer by evaluating its mRNA expression in both malignant and normal colonic tissue from patients with colorectal carcinomas with and without disease relapse. Methods: Publicly available expression microarray data were analyzed to reveal elevated levels of NFY-C in patients with colorectal carcinoma who relapsed compared to patients who remained disease free. The mRNA levels of NFY-C were evaluated by quantitative RT-PCR in 81 neoplastic colorectal tissue specimens and 23 normal tissue specimens from patients with colorectal cancer who had undergone curative resections at the University Hospital of Patras, Greece, between 1995 and 2005. The mRNA levels were analysed in relation to clinicopathological parameters. Results: No significant difference was found in the expression levels of NFY-C between normal and malignant tissues. The expression levels of NFY-C were not related to age, gender, grade, stage or primary site of the disease. However, a statistically significant difference (p=0.02) was observed in NFY-C levels between patients with and without disease recurrence. More specifically, patients with low NFY-C levels relapsed more often than patients who overexpressed NFY-C. Nevertheless, the expression was not related to time to disease progression. Finally, patients with higher NFY-C expression levels seem to have improved survival, compared to patients with low NFY-C expression levels although the difference was not statistically significant. Conclusions: Expression levels of NFY-C seem to be associated with disease recurrence. The role of NFY-C in colorectal cancer warrants further investigation. No significant financial relationships to disclose.


2021 ◽  
Vol 8 ◽  
Author(s):  
Zongxia Wang ◽  
Lizhou Jia ◽  
Yushu sun ◽  
Chunli Li ◽  
Lingli Zhang ◽  
...  

Trophoblast cell surface protein 2 (Trop2) is one of the cancer-related proteins that plays a vital role in biological aggressiveness and poor prognosis of colorectal cancer (CRC). The study of the Trop2 related network is helpful for us to understand the mechanism of tumorigenesis. However, the effects of the related proteins interacting with Trop2 in CRC remain unclear. Here, we found that coronin-like actin-binding protein 1C (CORO1C) could interact with Trop2 and the expression of CORO1C in CRC tissues was higher than that in paracarcinoma tissues. The expression of CORO1C was associated with histological type, lymph node metastasis, distant metastasis, AJCC stage, venous invasion, and perineural invasion. The correlation between CORO1C expression and clinical characteristics was analyzed demonstrating that high CORO1C expression in CRC patients were associated with poor prognosis. Furthermore, CORO1C knockdown could decrease the cell proliferation, colony formation, migration and invasion in vitro and tumor growth in vivo. The underlying mechanisms were predicted by bioinformatics analysis and verified by Western blotting. We found that PI3K/AKT signaling pathway was significantly inhibited by CORO1C knockdown and the tuomr-promoting role of CORO1C was leastwise partly mediated by PI3K/AKT signaling pathway. Thus, CORO1C may be a valuable prognostic biomarker and drug target in CRC patients.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yoon Ho Ko ◽  
Young-Seok Cho ◽  
Hye Sung Won ◽  
Ho Jung An ◽  
Der Sheng Sun ◽  
...  

Background/Aim.Bax-interacting factor-1 (Bif-1) plays a crucial role in apoptosis and autophagy. The aim of this study was to evaluate Bif-1 protein expression and its prognostic significance in colorectal cancer (CRC).Methods.We analyzed Bif-1 protein expression in 251 resected specimens from patients with CRC by immunohistochemistry using tissue microarray.Results.Low Bif-1 expression was observed in 131 patients (52.2%) and high Bif-1 expression in 120 patients (47.8%). No significant differences were observed in clinicopathological parameters between patients with high and low Bif-1 expression. Kaplan-Meier survival analysis showed no difference in survival between patients with high and low Bif-1 expression. Stratified analysis of Bif-1 according to TNM stage demonstrated that low Bif-1 expression was significantly associated with a poor outcome in patients with stages I and II (P=0.034). Stratified multivariate analysis demonstrated that low Bif-1 expression was an independent indicator of poor prognosis (hazard ratio, 0.459; 95% confidence interval, 0.285–0.739;P=0.001).Conclusion.Patients with low levels of Bif-1 expression have shortened survival rates in CRC of stages I and II. This suggests that Bif-1 protein expression may be a useful prognostic marker in early-stage CRC.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ying Huang ◽  
Guihua Wang ◽  
Chunmei Zhao ◽  
Rong Geng ◽  
Shu Zhang ◽  
...  

Colorectal cancer (CRC) is a complex and heterogeneous disease with four consensus molecular subtypes (CMS1-4). LTBP2 is a member of the fibrillin/LTBP super family and plays a critical role in tumorigenesis by activating TGF-β in the CMS4 CRC subtype. So far, the expression and prognostic significance of LTBP2 in CRC remains obscure. In this study, we aimed to analyze the mRNA and protein expression levels of LTBP2 in CRC tissues and then estimate their values as a potential prognostic biomarker. We detected the mRNA expression of LTBP2 in 28 cases of fresh CRC tissues and 4 CRC cell lines and the protein expression of LTBP2 in 483 samples of CRC tissues, matched tumor-adjacent tissues, and benign colorectal diseases. LTBP2 protein expression was then correlated to patients’ clinical features and overall survival. Both LTBP2 mRNA and protein expression levels in CRC tissues were remarkably superior to those in adjacent normal colorectal tissues (P=0.0071 and P<0.001, respectively), according to TCGA dataset of CRC. High LTBP2 protein expression was correlated with TNM stage (P<0.001), T stage (P<0.001), N stage (P<0.001), and M stage (P<0.001). High LTBP2 protein expression was related to poor overall survival in CRC patients and was an independent prognostic factor for CRC. LTBP2 mRNA expression was especially higher in the CMS4 subtype (P<0.001), which was confirmed in CRC cell lines. Our data suggested that LTBP2 may act as an oncogene in the development of colorectal cancer and have important significance in predicting CRC prognosis. LTBP2 could be a novel biomarker and potential therapeutic target for mesenchymal colorectal cancer and can improve the outcome of high-risk CRC.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Lui Ng ◽  
Timothy Wan ◽  
Ariel Chow ◽  
Deepak Iyer ◽  
Johnny Man ◽  
...  

Colorectal cancer (CRC) is one of the most common and fatal malignancies worldwide. The poor prognosis of colorectal cancer patients is due to development of chemoresistance and cancer metastasis. Recently osteopontin (OPN) has been associated with stem-like properties in colorectal cancer. This study further examined the clinicopathological significance of OPN in CRC and its effect on chemoresistance and transcription of stem cell markers. We examined the transcription level of OPN in 84 CRC patients and correlated the expression with their clinicopathological parameters. The associations of OPN overexpression with transcription of stem cell markers and response to chemotherapy in DLD1-OPN overexpressing clones and CRC patients were also investigated. Our results showed that OPN was significantly overexpressed in CRC, and its overexpression correlated with tumor stage and poor prognosis. Overexpression of CRC induced OCT4 and SOX2 expressionin vitroand correlated with SOX2 overexpression in CRC patients. In addition, DLD1-OPN overexpressing cells showed enhanced ability to survive upon oxaliplatin treatment, and OPN expression was higher in CRC patients who were resistant to oxaliplatin-involved chemotherapy treatment. Thus, CRC cells overexpressing OPN demonstrated stem-like properties and OPN inhibition is a potential therapeutic approach to combat CRC progression and chemoresistance.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Sepideh Kadkhoda ◽  
Reza Taslimi ◽  
Farshid Noorbakhsh ◽  
Farzaneh Darbeheshti ◽  
Javad Tavakkoly Bazzaz ◽  
...  

Abstract Introduction Colorectal cancer (CRC) is one of the most frequent neoplasms in the world. Based on the emerging role of noncoding RNAs, particularly circular RNAs in pathogenesis of cancers, we designed this study to inspect the expression levels of a circ0009910-mediated regulatory pathway in colorectal cancer. Methods After bioinformatics analyses and construction of putative circ0009910/ miR-145-5p/PEAK1 pathway, the expression levels of these components were evaluated in 50 CRC tissues and adjacent specimens by quantitative real-time PCR. Moreover, we appraised the correlation coefficients between these transcripts and calculated the correlation between circ0009910 expression levels with clinicopathological features of patients. Results Circ0009910 and PEAK1 were significantly upregulated, while miR-145-5p was decreased in CRC samples compared with adjacent tissues (p < 0.05). Moreover, statistically significant correlations were observed between expression levels of circ0009910, miR-145-5p, and PEAK1. We also reported considerable correlations between circ0009910 expression and clinicopathological parameters including sex and perineural invasion. Finally, ROC curve analysis showed circ0009910 level as a discriminative biomarker for CRC. Conclusion For the first time, we could introduce circ0009910 as an important biomarker in CRC. Collectively, this investigation helped us to identify a newly diagnosed pathway in CRC that can be a potential axis for designing effective drugs for treatment of CRC patients.


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.


2021 ◽  
Vol 25 (2) ◽  
pp. 544-550
Author(s):  
Jalal Jalal ◽  
Zheen Othman ◽  
Payman Anwar

Background and objective: Colorectal cancer is a heterogeneous malignancy characterized by a wide range of genetic and epigenetic alterations. Clusterin is a heterodimeric glycoprotein widely expressed in a variety of tissues and secreted in many body fluids. Increased clusterin expression has been reported in the normal colonic mucosa, benign polyps, and colorectal carcinoma. This study aimed to detect the frequency of the clusterin immunoexpression in colorectal carcinoma and determine its association with some clinicopathological parameters. Methods: Sixty formalin-fixed paraffin-embedded sections of colorectal adenocarcinoma were obtained and randomly selected from the histopathology laboratory at Rizgary Teaching Hospital and some private histopathology laboratories in Erbil city over two years between December 2016 and December 2018. All patients had been diagnosed to have primary colorectal adenocarcinoma and had undergone surgery. The clinicopathological characteristics of the tumors were revised, and the specimens were analyzed immunohistochemically using anticlusterin mouse monoclonal antibody. Results: Twenty eight cases (46.6%) were labeled as clusterin positive, while 32 cases (53.4%) were negative for clusterin expression. Clusterin expression was significantly associated with the tumor type (Non-mucinous) (P = 0.01) and tumor grade (well to moderately differentiated) (P = 0.03). At the same time, no significant association was found between clusterin immunoexpression and other clinicopathological characteristics like age, gender, tumor site, and tumor stage. Conclusion: Our study indicated that clusterin is overexpressed in some colorectal carcinomas and is significantly associated with histological type and grade. These results suggest that clusterin may play a role in colorectal carcinogenesis. Further studies are required to understand the possible mechanism of clusterin association with carcinogenesis and cancer progression. Keywords: Colorectal cancer; Clusterin; Immunohistochemistry.


Sign in / Sign up

Export Citation Format

Share Document