scholarly journals CILP2 overexpression correlates with tumor progression and poor prognosis in patients with colorectal cancer in the study of The Cancer Genome Atlas (TCGA) and our cohort analysis

2020 ◽  
Author(s):  
Feng Huang ◽  
Yuanfei Peng ◽  
Qing Ye ◽  
Jinhu Chen ◽  
Yangming Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Poor Prognosis ◽  
Clinical Stage ◽  
Cohort Analysis ◽  
Genetic Alterations ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Log Rank Test ◽  
Bioinformatical Analysis

Abstract Background: Genetic alterations play an important role in the progression of colorectal cancer. Identifying new biomarkers to assess the prognosis of patients with colorectal cancer is critical. Cartilage Intermediate Layer Protein 2 (CILP2) gene, screened from the TCGA database by bioinformatics, may be closely related to the progression of colorectal cancer. 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 colorectal cancer and matched adjacent normal tissues. The expression at the protein level was detected in 64 pairs of colorectal cancer 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 colorectal cancer 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 colorectal cancer.

scholarly journals CILP2 overexpression correlates with tumor progression and poor prognosis in patients with colorectal cancer in The Cancer Genome Atlas (TCGA) study

2020 ◽  
Author(s):  
Feng Huang ◽  
Yuanfei Peng ◽  
Qing Ye ◽  
Jinhu Chen ◽  
Yangming Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Clinical Stage ◽  
Genetic Alterations ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Log Rank Test ◽  
Bioinformatical Analysis

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.

scholarly journals CILP2 overexpression correlates with tumor progression and poor prognosis in patients with colorectal cancer in The Cancer Genome Atlas (TCGA) study

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Feng Huang ◽  
Yuanfei Peng ◽  
Qing Ye ◽  
Jinhu Chen ◽  
Yangming Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Clinical Stage ◽  
Genetic Alterations ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Log Rank Test ◽  
Bioinformatical Analysis

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.

scholarly journals CILP2 overexpression predicts poor prognosis in colorectal cancer

2020 ◽  
Author(s):  
Feng Huang ◽  
Yuanfei Peng ◽  
Qing Ye ◽  
Jinhu Chen ◽  
Yangming Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Clinical Stage ◽  
Mrna Level ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Log Rank Test ◽  
Bioinformatical Analysis

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.

scholarly journals CILP2 overexpression correlates with tumor progression and predicts poor outcome in patients with colorectal cancer

2020 ◽  
Author(s):  
Feng Huang ◽  
Yuanfei Peng ◽  
Qing Ye ◽  
Jinhu Chen ◽  
Yangming Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Clinical Stage ◽  
Mrna Level ◽  
Genetic Alterations ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Log Rank Test ◽  
Bioinformatical Analysis

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 colorectal cancer is critical. Cartilage Intermediate Layer Protein 2 (CILP2) gene, screened from the TCGA database by bioinformatics, may be closely related to the progression of colorectal cancer. 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 significant higher expressed in the colorectal cancer 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 colorectal cancer.

scholarly journals CILP2 overexpression predicts poor prognosis in colorectal cancer

2020 ◽  
Author(s):  
Feng Huang ◽  
Yuanfei Peng ◽  
Qing Ye ◽  
Jinhu Chen ◽  
Yangming Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Clinical Stage ◽  
Rank Test ◽  
P Value ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Log Rank Test ◽  
Bioinformatical Analysis

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

scholarly journals Upregulation of GNPNAT1 Predicts Poor Prognosis and Correlates With Immune Infiltration in Lung Adenocarcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Wenting Liu ◽  
Kaiting Jiang ◽  
Jingya Wang ◽  
Ting Mei ◽  
Min Zhao ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathways ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Clinical Stage ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Clinical Value ◽  
Cox Regression Analysis ◽  
Normal Tissues

BackgroundGlucosamine 6-phosphate N-acetyltransferase (GNPNAT1) is a key enzyme in the hexosamine biosynthetic pathway (HBP), which functions as promoting proliferation in some tumors, yet its potential biological function and mechanism in lung adenocarcinoma (LUAD) have not been explored.MethodsThe mRNA differential expression of GNPNAT1 in LUAD and normal tissues was analyzed using the Cancer Genome Atlas (TCGA) database and validated by real-time PCR. The clinical value of GNPNAT1 in LUAD was investigated based on the data from the TCGA database. Then, immunohistochemistry (IHC) of GNPNAT1 was applied to verify the expression and clinical significance in LUAD from the protein level. The relationship between GNPNAT1 and epigenetics was explored using the cBioPortal database, and the miRNAs regulating GNPNAT1 were found using the miRNA database. The association between GNPNAT1 expression and tumor-infiltrating immune cells in LUAD was observed through the Tumor IMmune Estimation Resource (TIMER). Finally, Gene set enrichment analysis (GSEA) was used to explore the biological signaling pathways involved in GNPNAT1 in LUAD.ResultsGNPNAT1 was upregulated in LUAD compared with normal tissues, which was verified through qRT-PCR in different cell lines (P &lt; 0.05), and associated with patients’ clinical stage, tumor size, and lymphatic metastasis status (all P &lt; 0.01). Kaplan–Meier (KM) analysis suggested that patients with upregulated GNPNAT1 had a relatively poor prognosis (P &lt; 0.0001). Furthermore, multivariate Cox regression analysis indicated that GNPNAT1 was an independent prognostic factor for LUAD (OS, TCGA dataset: HR = 1.028, 95% CI: 1.013–1.044, P &lt; 0.001; OS, validation set: HR = 1.313, 95% CI: 1.130–1.526, P &lt; 0.001). GNPNAT1 overexpression was correlated with DNA copy amplification (P &lt; 0.0001), low DNA methylation (R = −0.52, P &lt; 0.0001), and downregulation of hsa-miR-30d-3p (R = −0.17, P &lt; 0.001). GNPNAT1 expression was linked to B cells (R = −0.304, P &lt; 0.0001), CD4+T cells (R = −0.218, P &lt; 0.0001), and dendritic cells (R = −0.137, P = 0.002). Eventually, GSEA showed that the signaling pathways of the cell cycle, ubiquitin-mediated proteolysis, mismatch repair and p53 were enriched in the GNPNAT1 overexpression group.ConclusionGNPNAT1 may be a potential prognostic biomarker and novel target for intervention in LUAD.

scholarly journals EYA4 could be an indicator signifying colorectal cancer sufferers' prognoses

2020 ◽  
Author(s):  
Yang Yan ◽  
Xiaohui Du ◽  
Shaoyou Xia ◽  
Songyan Li ◽  
Da Teng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Survival Curve ◽  
Mrna Level ◽  
Clinicopathological Characteristics ◽  
Rank Test ◽  
Normal Tissues ◽  
Log Rank Test ◽  
Low Expression

Abstract Background Eyes absent 4 (EYA4) is involved in various biological processes. The aim of this study was to investigate the expression of EYA4 and its prognostic value in colorectal cancer (CRC). Methods The mRNA level of EYA4 in diseased tissues and adjacent normal tissues of CRC patients were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The association between EYA4 expression and clinicopathological characteristics was analyzed by χ2 test. Kaplan-Meier analysis with log rank test was performed to evaluate the effects of EYA4 expression on overall survival of CRC patients. Cox regression model was applied for prognosis analysis in CRC. Results The mRNA level of EYA4 was significantly decreased in CRC tissues compared with that in the adjacent normal tissue (P < 0.01). And its expression was affected by DUKE stage (P = 0.034), differentiation (P = 0.027) and vascular invasion (P = 0.037). Survival curve showed that patients with low expression of EYA4 had a significantly shorter overall survival than those with high expression (log rank test, P = 0.008). Low expression of EYA4 (HR = 1.989, 95%CI = 1.090-3.62902, P = 0.025) was an independent biomarker for poor prognosis in CRC patients. Conclusion EYA4 expression is decreased in CRC patients and negatively correlated with aggressive tumor progression. EYA4 may be a potential prognostic biomarker for CRC.

scholarly journals Cytoplasmic Expression of DCLK1-S, a Novel DCLK1 Isoform, Is Associated with Tumor Aggressiveness and Worse Disease-Specific Survival in Colorectal Cancer

2021 ◽  
Author(s):  
Elham Kalantari ◽  
Roya Ghods ◽  
Leili Saeednejad Zanjani ◽  
Mandana Rahimi ◽  
Leila Eini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rank Test ◽  
Disease Specific Survival ◽  
Tumor Aggressiveness ◽  
Cytoplasmic Expression ◽  
Normal Tissues ◽  
Log Rank Test ◽  
Disease Specific

Abstract Isoform-specific function of doublecortin-like kinase 1(DCLK1) has highlighted key role of the DCLK1-S (short isoform) in maintenance, progression, and invasion of tumor. Therefore, this study was designed to produce an anti-DCLK1-S polyclonal antibody in order to specifically evaluate expression pattern and clinical significance of DCLK1-S in a well-defined tissue microarray (TMA) series of colorectal tissues including 348 colorectal cancer (CRC) and 51 adjacent normal tissues during a follow-up period of 108 months. Expression of DCLK1-S was significantly higher in CRC samples compared to adjacent normal samples (P < 0.001). Cytoplasmic expression of DCLK1-S was significantly higher in the tumors at advanced stage of the cancer and with poorer differentiation (P<0.001, P= 0.02). The patients with CRC whose tumors showed higher cytoplasmic expression of DCLK1-S had worse disease-specific survival (DSS) (log-rank test, P = 0.03) and 5-year DSS rates (P= 0.01). Additionally, an improved prognostic value was observed in the patients with CRC with high DCLK1-S expression vs. its moderate expression (HR: 2.70, 95% CI: 0.98-7.38; p =0.04) by multivariate analysis. Our findings strongly supported that high cytoplasmic expression of DCLK1-S compared to its moderate expression could be considered as an independent prognostic factor influencing DSS. Taken together, DCLK1-S can be a promising prognostic candidate and targeted-therapeutic indicator for effective treatment of CRC.

Prediction of lymph node metastasis and prognosis in colorectal cancer patients using slug and vimentin expression.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14029-e14029
Author(s):  
Yuji Toiyama ◽  
Hiromi Yasuda ◽  
Susumu Saigusa ◽  
Yoshinaga Okugawa ◽  
Koji Tanaka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Poor Prognosis ◽  
Rank Test ◽  
Vimentin Expression ◽  
Invasion And Migration ◽  
Node Metastasis ◽  
Log Rank Test ◽  
And Migration

e14029 Background: Slug plays a critical role in regulating the epithelial-mesenchymal transition (EMT) by down-regulation of epithelial markers and up-regulation of mesenchymal markers. The purpose of the present study was to evaluate the clinical significance of Slug and Vimentin expression in colorectal cancer (CRC) and to perform in vitro characterization of Slug’s function. Methods: At first, the biological role of Slug in CRC was assessed by RNA interference in CRC cell lines to assess tumor progression, invasion and migration. We next analyzed Slug and Vimentin expression in surgical tissue specimens from 181 CRC patients by quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. Results: Knockdown of Slug in siRNA knockdown studies resulted in induction of EMT markers, inhibited cancer cell proliferation, invasion and migration abilities. Slug and Vimentin expression in cancer tissues was significantly higher in patients with high T stage, lymph node involvement, liver metastasis and advanced TNM stage. We also observed a significant correlation between Slug and Vimentin expression in CRC (rho = 0.467). Increased Slug and Vimentin expression were significantly associated with poor prognosis in Stage I-IV (p<0.0001, p=0.0005, log-rank test) and Stage II (p= 0.04, p=0.012, log-rank test) Furthermore, increased Slug expression was an independent predictive marker of lymph node metastasis (p=0.012) and prognostic factor (p= 0.025). Conclusions: Our data demonstrate that evaluation of Slug and Vimentin could be valuable in the identification of patients with lymph node metastasis or poor prognosis in CRC.

Cytoplasmic expression of DCLK1-S, a novel DCLK1 isoform, is associated with tumor aggressiveness and worse disease-specific survival in colorectal cancer

2021 ◽  
pp. 1-13
Author(s):  
Elham Kalantari ◽  
Roya Ghods ◽  
Leili Saeednejad Zanjani ◽  
Mandana Rahimi ◽  
Leila Eini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rank Test ◽  
Disease Specific Survival ◽  
Tumor Aggressiveness ◽  
Cytoplasmic Expression ◽  
Normal Tissues ◽  
Log Rank Test ◽  
Disease Specific

BACKGROUND: Isoform-specific function of doublecortin-like kinase 1 (DCLK1) has highlighted the key role of the DCLK1-S (short isoform) in the maintenance, progression, and invasion of the tumor. OBJECTIVE: This study was designed to produce an anti-DCLK1-S polyclonal antibody to evaluate DCLK1-S in human colorectal cancer (CRC) specifically. METHODS: The expression pattern and clinical significance of DCLK1-S were assessed in a well-defined tissue microarray (TMA) series of 348 CRC and 51 adjacent normal tissues during a follow-up period of 108 months. RESULTS: Expression of DCLK1-S was significantly higher in CRC samples compared to adjacent normal samples (P< 0.001). Cytoplasmic expression of DCLK1-S was significantly higher in the tumors at the advanced stage of cancer and with poorer differentiation (P< 0.001, P= 0.02). The patients with CRC whose tumors showed higher cytoplasmic expression of DCLK1-S had worse disease-specific survival (DSS) (log-rank test, P= 0.03) and 5-year DSS rates (P= 0.01). Additionally, an improved prognostic value was observed in the patients with CRC with high DCLK1-S expression vs. its moderate expression (HR: 2.70, 95% CI: 0.98–7.38; p= 0.04) by multivariate analysis. CONCLUSIONS: Our findings strongly supported that high cytoplasmic expression of DCLK1-S compared to its moderate expression could be considered an independent prognostic factor influencing DSS.

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