Long Noncoding RNAZEB1-AS1 Expression Predicts Progression and Poor Prognosis of Colorectal Cancer

2017 ◽  
Vol 32 (4) ◽  
pp. 428-433 ◽  
Author(s):  
Jining Fu ◽  
Yongyuan Cui

Background ZEB1-AS1 acts as an oncogene in hepatocellular carcinoma, accelerating tumor growth and promoting metastasis. However, its roles in colorectal cancer (CRC) remain unclear. Methods In this study, we determined the expression of ZEB1-AS1 in CRC tissues by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, we investigated the relationship between various clinicopathological features of CRC patients and ZEB1-AS1 expression, and evaluated the diagnostic and prognostic value of ZEB1-AS1 in CRC. Results We found that ZEB1-AS1 expression was significantly higher in CRC tissues than in adjacent normal colorectal tissues. Moreover, its expression was significantly correlated with tumor size, differentiation degree, TNM grade, metastasis, depth of invasion and Dukes' classification, but not with sex, age, location and organization. In addition, at the optimal cutoff value of 2.340, the values of diagnostic sensitivity and specificity amounted to 63.0% and 90.7%, respectively, with an area under the curve (AUC) of 0.846 (95% CI, 0.797-0.895). Finally, CRC patients of the high ZEB1-AS1 expression group had a poorer prognosis and a significantly lower survival rate than those of the low expression group, and Cox regression analysis indicated that ZEB1-AS1 expression and metastasis were independent predictors of poor prognosis. Conclusions Our data suggest that ZEB1-AS1 has no obvious early diagnostic value, but it may be utilized as a new prognostic biomarker for CRC.

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Qi Zhang ◽  
Jun Di ◽  
Zhiyu Ji ◽  
Aoning Mi ◽  
Quanying Li ◽  
...  

Kinesin family member 20A (KIF20A) has been recently reported to be upregulated and associated with increased invasiveness and metastasis in several malignancies. However, the role of KIF20A in colorectal cancer (CRC) is still unclear. This study is aimed at investigating the potential roles of KIF20A in the development of CRC. The results of bioinformatics analysis, immunohistochemical staining, and Western blot analysis showed that KIF20A was overexpressed in CRC tissues compared with adjacent normal tissues. High expression of KIF20A in CRC tissues was associated with depth of invasion, lymphatic node metastasis, distant metastasis, and TNM stage. Moreover, the Kaplan-Meier survival analysis showed that CRC patients with high KIF20A expression had poor prognoses. Cox regression analysis revealed that KIF20A was an independent prognostic factor in patients with CRC. Further studies suggested that knockdown of KIF20A was able to reduce cell proliferation and migration by inhibiting the JAK/STAT3 pathway. Taken together, we propose that KIF20A plays a critical role in the tumorigenesis and tumor progression of colorectal cancer and could represent a potential therapeutic target for CRC.


2019 ◽  
Vol 17 ◽  
pp. 205873921984554
Author(s):  
Yanjuan Cai ◽  
Shutong Zhuang ◽  
Hongpeng Liu ◽  
Jianfu Qiu ◽  
Li Zeng

Emerging studies have showed that long-chain non-coding RNA DMTF1v4 might participate in the process of multidrug resistance phenotype of gastric cancer. However, its expression and function in colorectal cancer (CRC) is still unknown. In this study, we discovered that DMTF1v4 was generally 5.15 ± 1.67 times upregulated in CRC tissues compared to the adjacent normal tissues. Moreover, the expression level of DMTF1v4 was closely related to the distant metastasis of tumor, but it was not related to age, sex, tumor location, tumor staging, depth of invasion, lymph node metastasis, and differentiation level. Survival analysis showed that the overall survival rate of patients with high expression of DMTF1v4 was 45.0% in cancer tissues, which was significantly lower than 82.5% of DMTF1v4 low expression patients (χ2 = 11.562, P < 0.01). The results of univariate COX regression analysis showed that DMTF1v4, TNM (tumor, node, metastasis) staging, distant metastasis, and tumor differentiation were closely related to the prognosis of patients ( P < 0.05). Multivariate COX regression analysis showed that DMTF1v4 and distant metastasis could be independent prognostic factors for CRC patients. In conclusion, this study revealed that DMTF1v4 might promote the development of CRC, which can be used as an independent factor to judge the prognosis of CRC.


2020 ◽  
Author(s):  
Feng Huang ◽  
Yuanfei Peng ◽  
Qing Ye ◽  
Jinhu Chen ◽  
Yangming Li ◽  
...  

Abstract Background: Genetic alterations play an important role in the progression of colorectal cancer (CRC). Identifying new biomarkers to assess the prognosis of patients with CRC is critical. Cartilage Intermediate Layer Protein 2 (CILP2) gene, screened from the TCGA database by bioinformatics, may be closely related to the progression of CRC. CILP2 was barely reported with clinical features of tumors.Materials and methods: Clinical information and RNA-seq data were derived from the TCGA colorectal carcinoma cohort. CILP2 expression at mRNA level was estimated by bioinformatical analysis of TCGA cases. Tissue microarray (TMA) was constructed containing paraffin-embedded 64 pairs of CRC and matched adjacent normal tissues. The expression at the protein level was detected in 64 pairs of CRC and matched adjacent normal tissues by immunohistochemical analysis. CILP2 expression level and its clinical value were estimated by bioinformatical analysis with linear and logistic regression. Survival analysis was performed between high and low groups of CILP2 expression by Cox regression analysis, and the P-value was calculated by the log-rank test. Kaplan-Meier curves were tested by the log-rank test.Results: CILP2 was statistically significantly higher expressed in the CRC tissues when compared with paired adjacent normal tissues in the TCGA cohort (P<0.001) and in the TMA cohort (P=0.001). Also, CILP2 high-expression was strongly correlated with T3/4 stage (P=0.001), N1/2/3 stage (P=0.005), M1 stage (P=0.048), and higher clinical stage (UICC 2010 stage) (P<0.001) in TCGA cohort, and also positively associated with T3/4 stage (P=0.022) and higher clinical stage (UICC 2010 stage) (P=0.03) in TMA cohort. Furthermore, CILP2 overexpression predicted poor prognosis and could be as an independent prognostic factor (P=0.003).Conclusion: We revealed that CILP2 is associated with advanced stages and could play a role as an independent predictor of poor survival in CRC.


2020 ◽  
Author(s):  
HJ Li ◽  
YL Wang ◽  
L Ming ◽  
XQ Guo ◽  
YL Li ◽  
...  

Screening and therapeutic programs for colorectal cancer (CRC) are invasive or not effective and unable to meet patient needs. Major advances in immunogenomics may change this status but need more exploration. Differentially expressed genes and immune-related genes (IRGs) were identified by computational methods. A prognostic model was established and validated based on survival-related IRGs via stepwise multivariate Cox regression analysis. Nine IRGs were selected and identified as survival-related genes. A 7-gene prognostic model could offer a preliminary and valid determination of risk in CRC patients. The area under the curve of the receiver operating characteristic was 0.672. The 7-gene prognostic model might be used as a novel prognostic tool in CRC patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Jingsun Wei ◽  
Xiaoxu Ge ◽  
Yang Tang ◽  
Yucheng Qian ◽  
Wei Lu ◽  
...  

Purpose. Colorectal cancer is one of the most common malignant primary tumors, prone to metastasis, and associated with a poor prognosis. As autophagy is closely related to the development and treatment of colorectal cancer, we investigated the potential prognostic value of long noncoding RNA (lncRNA) associated with autophagy in colorectal cancer. Methods. In this study, we acquired information on the expression of lncRNAs in colorectal cancer from the Cancer Genome Atlas (TCGA) database and found that 860 lncRNAs were associated with autophagy-related genes. Subsequently, univariate Cox regression analysis was used to investigate 32 autophagy-related lncRNAs linked to colon cancer prognosis. Subsequently, eight of the 32 autophagy-related lncRNAs (i.e., long intergenic nonprotein coding RNA 1503 [LINC01503], ZEB1 antisense RNA 1 [ZEB1-AS1], AC087481.3, AC008760.1, AC073896.3, AL138756.1, AL022323.1, and TNFRSF10A-AS1) were selected through multivariate Cox regression analysis. Based on these autophagy-related lncRNAs, a risk signature was constructed, and the patients were divided into high- and low-risk groups. Results. The high-risk group’s overall survival time was significantly shorter than that of the low-risk group p < 0.0001 . Receiver operating characteristic curve analysis was performed to further confirm the validity of the model (area under the curve: 0.689). Moreover, multivariate regression suggested that the risk score was a significant prognostic risk factor in colorectal cancer. Gene set enrichment analysis showed that these gene sets are significantly enriched in cancer-related pathways, such as Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling. Conclusion. The risk signature of eight autophagy-related lncRNAs has prognostic potential for colorectal cancer. These autophagy-related lncRNAs may play a vital role in the biology of colorectal cancer.


Author(s):  
Chul Seung Lee ◽  
In Hye Song ◽  
Ahwon Lee ◽  
Jun Kang ◽  
Yoon Suk Lee ◽  
...  

Targeted next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. We included 145 CRC patients who underwent surgery. We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS. Approximately 97.9% (142) of patients showed somatic mutations. Frequent mutations were observed in TP53 (70%), KRAS (49%), and APC (47%). TP53 mutations were significantly linked to higher overall stage (p=0.038) and lower disease-free survival (DFS) (p=0.039). ATM mutation was significantly associated with higher tumor stage (p=0.012) and shorter overall survival (OS) (p=0.041). Stage 3 and 4 patients with ATM mutations (p=0.023) had shorter OS, and FBXW7 mutation was significantly associated with shorter DFS (p=0.002). In multivariate Cox regression analysis, ATM mutation was an independent biomarker for poor prognosis of OS (p=0.022). TP53 and FBXW7 mutations are independent biomarkers for poor prognosis of DFS (p=0.042 and 0.030, respectively). A comprehensive analysis of the molecular markers for CRC can provide insights into the mechanisms underlying disease progression and help optimize a personalized therapy.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Feng Huang ◽  
Yuanfei Peng ◽  
Qing Ye ◽  
Jinhu Chen ◽  
Yangming Li ◽  
...  

Abstract Background Genetic alterations play an important role in the progression of colorectal cancer (CRC). Identifying new biomarkers to assess the prognosis of patients with CRC is critical. Cartilage intermediate layer protein 2 (CILP2) gene, screened from TCGA database by bioinformatics, may be closely related to the progression of CRC. CILP2 was barely reported with clinical features of tumors. Materials and methods Clinical information and RNA-seq data were derived from TCGA colorectal carcinoma cohort. CILP2 expression at mRNA level was estimated by bioinformatical analysis of TCGA cases. Tissue microarray (TMA) was constructed containing paraffin-embedded 64 pairs of CRC and matched adjacent normal tissues. The expression at the protein level was detected in 64 pairs of CRC and matched adjacent normal tissues by immunohistochemical analysis. CILP2 expression level and its clinical value were estimated by bioinformatical analysis with linear and logistic regression. Survival analysis was performed between high and low groups of CILP2 expression by Cox regression analysis, and the P value was calculated by the log-rank test. The Kaplan-Meier curves were tested by the log-rank test. Results CILP2 was statistically significantly higher expressed in the CRC tissues when compared with paired adjacent normal tissues in TCGA cohort (P < 0.001) and in the TMA cohort (P = 0.001). Also, CILP2 high expression was strongly correlated with T3/4 stage (P = 0.001), N1/2/3 stage (P = 0.005), M1 stage (P = 0.048), and higher clinical stage (UICC 2010 stage) (P < 0.001) in TCGA cohort, and also positively associated with T3/4 stage (P = 0.022) and higher clinical stage (UICC 2010 stage) (P = 0.03) in TMA cohort. Furthermore, CILP2 overexpression predicted poor prognosis and could be an independent prognostic factor (P = 0.003). Conclusion We revealed that CILP2 is associated with advanced stages and could play a role as an independent predictor of poor survival in CRC.


2020 ◽  
Author(s):  
Feng Huang ◽  
Yuanfei Peng ◽  
Qing Ye ◽  
Jinhu Chen ◽  
Yangming Li ◽  
...  

Abstract Background Cartilage Intermediate Layer Protein 2 (CILP2), a glycoprotein with mutations associated with abnormal blood lipid concentrations in normal and cardiovascular diseases patients, was barely reported with clinical features of tumors. We evaluated the role of CILP2 among all stages and histology in colorectal cancer (CRC) in the Cancer Genome Altas (TCGA), and furtherly verified using immunohistochemistry assay within human CRC tissues. Materials and methods Clinical information and RNA-seq data were derived from TCGA colorectal carcinoma cohort. CILP2 expression at mRNA level was estimated by bioinformatical analysis of TCGA cases. Tissue microarray (TMA) was constructed containing paraffin-embedded 64 pairs of CRC and matched adjacent normal tissues. The expression at protein level was detected in 64 pairs of CRC and matched adjacent normal tissues by immunohistochemical analysis. CILP2 expression level and its clinical value were estimated by bioinformatical analysis with linear and logistic regression. Survival analysis was performed between high and low groups of CILP2 expression by Cox regression analysis, and P value was calculated by log-rank test. Kaplan-Meier curves were tested by log-rank test. Results CILP2 was significantly higher expressed in the colorectal cancer tissues when compared with paired adjacent normal tissues in TCGA cohort (P < 0.001) and in TMA cohort (P = 0.001). In addition, CILP2 high-expression was strongly correlated with T3/4 stage (P = 0.001), N1/2/3 stage (P = 0.005), M1 stage (P = 0.048), and higher clinical stage (UICC 2010 stage) (P < 0.001) in TCGA cohort, and also positively associated with T3/4 stage (P = 0.022) and higher clinical stage (UICC 2010 stage) (P = 0.03) in TMA cohort. Furthermore, CILP2 overexpression predicted poor prognosis and could be as an independent prognostic factor (P = 0.003). Conclusion We revealed that CILP2 is associated with advanced stages and could play a role as an independent predictor of poor survival in colorectal cancer.


2020 ◽  
Author(s):  
Feng Huang ◽  
Yuanfei Peng ◽  
Qing Ye ◽  
Jinhu Chen ◽  
Yangming Li ◽  
...  

Abstract Background: Cartilage Intermediate Layer Protein 2 (CILP2), a glycoprotein with mutations associated with abnormal blood lipid concentrations in normal and cardiovascular diseases patients, was barely reported with clinical features of tumors. We evaluated the role of CILP2 among all stages and histology in colorectal cancer (CRC) in the Cancer Genome Altas (TCGA), and furtherly verified using immunohistochemistry assay within human CRC tissues. Materials and methods : Clinical information and RNA-seq data were derived from TCGA colorectal carcinoma cohort. CILP2 expression at mRNA level was estimated by bioinformatical analysis of TCGA cases. Tissue microarray (TMA) was constructed containing paraffin-embedded 64 pairs of CRC and matched adjacent normal tissues. The expression at protein level was detected in 64 pairs of CRC and matched adjacent normal tissues by immunohistochemical analysis. CILP2 expression level and its clinical value were estimated by bioinformatical analysis with linear and logistic regression. Survival analysis was performed between high and low groups of CILP2 expression by Cox regression analysis, and P value was calculated by log-rank test. Kaplan-Meier curves were tested by log-rank test. Results : CILP2 was significantly higher expressed in the colorectal cancer tissues when compared with paired adjacent normal tissues in TCGA cohort ( P <0.001) and in TMA cohort ( P =0.001). In addition, CILP2 high-expression was strongly correlated with T3/4 stage ( P =0.001), N1/2/3 stage ( P =0.005), M1 stage ( P =0.048), and higher clinical stage (UICC 2010 stage) ( P <0.001) in TCGA cohort, and also positively associated with T3/4 stage ( P =0.022) and higher clinical stage (UICC 2010 stage) ( P =0.03) in TMA cohort. Furthermore, CILP2 overexpression predicted poor prognosis and could be as an independent prognostic factor ( P =0.003). Conclusion : We revealed that CILP2 is associated with advanced stages and could play a role as an independent predictor of poor survival in colorectal cancer. Key words: CILP2; Colorectal cancer; TCGA; Immunohistochemistry; Prognosis


2020 ◽  
Vol 14 (12) ◽  
pp. 1127-1137
Author(s):  
Tong-Tong Zhang ◽  
Yi-Qing Zhu ◽  
Hong-Qing Cai ◽  
Jun-Wen Zheng ◽  
Jia-Jie Hao ◽  
...  

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.


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