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.

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.

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 ◽  
Polyclonal Antibody ◽  
Prognostic Significance ◽  
Rank Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Disease Specific Survival ◽  
Cytoplasmic Expression ◽  
Advanced Tumor ◽  
Disease Specific

Abstract Background: Oncogenic role of doublecortin-like kinase 1 (DCLK1) as a putative cancer stem cell (CSC) marker has been clarified in colorectal cancer (CRC). Isoform-specific function of DCLK1 has highlighted key role of the DCLK1-S (short isoform) in tumor maintenance, progression, and invasion. Considering the lack of commercial anti-DCLK1-S antibody suitable for immunohistochemical (IHC) application, this study was conducted to produce and validate an anti-DCLK1-S polyclonal antibody in order to specifically evaluate expression pattern and clinical significance of short isoform of DCLK1 in colorectal cancer tissues.Methods: Rabbit immunization was performed against a synthetic peptide corresponding to the published six specific amino acid sequences of DCLK1-S, and production of antibody was evaluated by enzyme-linked immunosorbent assay (ELISA). After IHC assessment of the purified anti-DCLK1-S polyclonal antibody, it was used to undertake a definitive study for determining prognostic significance of DCLK1-S expression in a well-defined tissue microarray (TMA) series including 348 CRC and 51 adjacent normal tissues with a follow-up period of 108 months. Results: Positive immunoreactivity of DCLK1-S was found in 84.2% of CRC samples. Cytoplasmic expression was the main localization of DCLK1-S compared to nuclear and membranous area of tumor cells. Expression of DCLK1-S in CRC samples was significantly higher compared to adjacent normal samples (P <0.001). A positive significant association was found between high cytoplasmic expression of DCLK1-S and advanced tumor, nodes, and metastases (TNM) stage (P<0.001) as well as the increased tumor differentiation (P= 0.02). Moreover, 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 rate (P= 0.01). Additionally, the improved prognostic value was seen in the patients with CRC with high DCLK1-S expression versus moderate expression (HR: 2.70, 95% CI: 0.98-7.38; p =0.04) by multivariate analysis.Conclusions: Our findings strongly supported that DCLK1-S isoform may play a crucial role in invasion, tumor aggressive behavior, and worsened DSS of the patients with CRC. Importantly, high cytoplasmic expression of DCLK1-S compared to moderate expression could be considered as an independent prognostic factor influencing DSS. Taken together, DCLK1-S can be a candidate as a promising prognostic and targeted-therapeutic indicator for effective treatment of CRC.

Triple-negative breast cancer survival in women age 75 and older.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1060-1060
Author(s):  
Judith April Malmgren ◽  
Henry G. Kaplan ◽  
Mary K. Atwood
Keyword(s):  
Breast Cancer ◽  
Older Women ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Rank Test ◽  
Disease Specific Survival ◽  
Younger Women ◽  
Log Rank Test ◽  
Disease Specific

1060 Background: Triple-negative breast cancer (TNBC) is associated with a high recurrence rate and poor prognosis, despite high initial response to chemotherapy. It is not known if TNBC patients 75 years older, an age group less likely to be treated with adjuvant chemotherapy, have the same mortality risk as younger women. Methods: We conducted a prospective cohort study of all women presenting with primary TNBC, age 21-89, stage I-III from 1998-2009 identified and tracked by our registry (n=529). Clinical characteristics were chart abstracted at diagnosis and follow up. The Kaplan-Meier method and log rank test were used for disease specific survival (DSS) and overall survival (OS) by age. Results: Mean follow up was 6.6 years, range 1.98-13.41 years. Distribution by age was 92% <75 years (n = 485) and 8% 75+ years (n = 44). The two age groups did not differ by histologic or nuclear grade, stage, or radiation therapy receipt (age 75+ by stage: I = 46%, II = 34%, III 21%, age <75: I = 37%, II = 46%, III = 17% [not significant]). Patients 75 and older were less likely to be treated with adjuvant chemotherapy (32% vs. 91%, Pearson chi square test = 119.32, p <.001). 5 year DSS was not significantly different for patients age <75 years compared to patients age 75+ years (85% vs. 84%). However, 5 year OS was significantly worse for 75 year and older patients (65%) compared to <75 year old patients (83%) (log rank test = 13.97, p < .001). Conclusions: In our institutional cohort, triple-negative breast cancer in older women had similar prognostic indicators (stage and histologic grade) compared to younger women and older women had equivalent disease specific survival in spite of substantially less chemotherapy treatment. At 5 years post diagnosis, women 75 years and older were 18% more likely to die of causes other than breast cancer.

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 Overhydration and low serum prealbumin predict peritoneal dialysis-related peritonitis in continuous ambulatory peritoneal dialysis patients

2020 ◽  
Author(s):  
Quyen Dao Bui Quy ◽  
Tuan Pham Ngoc Huy ◽  
Loc Nguyen Duc ◽  
My Pham Van ◽  
Dung Nguyen Huu ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Rank Test ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Low Education ◽  
Curve Model ◽  
Independent Risk Factors ◽  
Low Serum

Abstract Background: In this study, we focused on the role of overhydration (OH) and low serum prealbumin concentration in predicting 3-year peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients.Methods: We measured serum prealbumin concentration and OH by body composition monitor on 278 CAPD patients (159 males and 119 females) with mean age of 46 years and the median peritoneal dialysis (PD) duration of 21 months. PD-related peritonitis was collected for 3 years. Results: After the 3-year follow-up, 44 patients diagnosed PD-related peritonitis (15.8%). Low education, serum albumin, prealbumin, high CRP-hs and OH were independent risk factors for predicting peritonitis during 36 months in CAPD patients. Based on the ROC curve model and Kaplan–Meier analysis, we realized that patients with low prealbumin and high OH were the independent predictors of 3-year peritonitis in CAPD patients (Prealbumin: AUC = 0.838, cut-off value = 32.5 mg/dL, Se= 90.9%, Sp = 32.9%; OH: AUC = 0.851, cut-off value = 1.33 L, Se = 79.5%, Sp = 85.5%; and Log-rank test p < 0.001, respectively). Conclusion: Overhydration and low serum prealbumin level were the independent predictors of PD-related peritonitis in CAPD patients.

RADT-27. EFFECTIVENESS ANALYSIS OF RADIOTHERAPY FOR INTRACRANIAL RECURRENT EPENDYMOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi47-vi47
Author(s):  
Qingjun Hu ◽  
Mingyao Lai ◽  
Juan Li ◽  
Linbo Cai
Keyword(s):  
Survival Time ◽  
Rank Test ◽  
Who Grade ◽  
Radiotherapy Group ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Recurrent Ependymoma ◽  
Grade Ii

Abstract OBJECTIVE There is no standard treatment for recurrent ependymoma. This study aimed to investigated the role of radiotherapy in recurrent ependymoma. METHODS Retrospective analysis was performed on 49 cases of recurrent ependymoma diagnosed in Guangdong Sanjiu Brain Hospital from January 2008 to July 2020. Overall survival (OS) was calculated by Kaplan-Meier method and tested by Log-rank test. P &lt; 0.05 was considered statistically significant. RESULTS The median age was 7 years (range:1-57 yrs). Nineteen patients were with ependymoma WHO grade II while 30 were with grade III, respectively. Recurrence treatment: 14 cases received re-surgery, 23 cases received radiotherapy, among them 16 cases received re-radiotherapy. To May, 2021, the median follow-up time was 35 months (range 3-153). Median PFS time was 17 months after initial diagnosis, median PFS time was 8 months after treatment to recurrence disease, Median OS time is 39 months, and median OS time is 20 months after recurrence. The median survival time for recurrence was 48 months vs. 11 months (P =0.001) in the radiotherapy group vs. non-radiotherapy group,res; Re-radiotherapy combined with chemotherapy vs reradiotherapy alone (0.194); RRT combined with anti-angiogenesis therapy vs. RRT alone (0.688). CONCLUSION Radiotherapy can prolong the survival time of recurrent ependymoma, and concurrent therapy as chemotherapy or anti-angiogenesis therapy with RT does not seem to improve the prognosis. Therefore, radiotherapy can be used as the main treatment for recurrent ependymoma.

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 Evidence-based follow-up in colorectal cancer—quo vadis?

2019 ◽  
Vol 13 (1) ◽  
pp. 64-68 ◽  
Author(s):  
Manuel Maglione ◽  
Alexander Perathoner
Keyword(s):  
Colorectal Cancer ◽  
Computed Tomography ◽  
Carcinoembryonic Antigen ◽  
Western World ◽  
Disease Specific Survival ◽  
The Third ◽  
Computed Tomography Scans ◽  
Disease Specific ◽  
Intensive Surveillance

SummaryColorectal cancer is the third most common and the third most lethal cancer disease in the western world. As most patients undergo treatment with curative intent at initial diagnosis, postoperative surveillance protocols have been established with the primary aim to detect possible disease recurrence in an early resectable stage. Various international guidelines recommend an intensive surveillance protocol over a 5-year time period. These guidelines are based on the reported significant benefit regarding overall patient survival, and on the observation that 90% of recurrences occur within the first 5 years following resection. Surveillance protocols include regular clinical examinations, measurement of the carcinoembryonic antigen, computed tomography scans and regular endoscopies. While there is plenty of evidence regarding the scheduling of endoscopies, the frequency of carcinoembryonic antigen measurements and computed tomography scans has been ever since under debate. The benefit of intensive compared to low frequency surveillance protocols regarding disease-specific survival has never been shown. Moreover, recent meta-analyses and randomized controlled trials challenge current guidelines. Intensive carcinoembryonic antigen assessment and computed tomography scan follow-up protocols seem to fail in generating better overall and disease-specific survival in colorectal cancer patients compared to less intensive surveillance strategies. This change over the last few decades parallels the treatment evolution of colorectal cancer from a primarily surgical to a multidisciplinary task. Instead of advocating a reduction of the follow-up intensity, these findings should stimulate the colorectal oncology field to move from a one-fits-all to a patient-centered surveillance.

scholarly journals The Effect of Cholecystectomy on the Risk of Colorectal Cancer in Patients with Gallbladder Stones

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 550 ◽  
Author(s):  
Chien-Hua Chen ◽  
Cheng-Li Lin ◽  
Chia-Hung Kao
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Cumulative Incidence ◽  
Positive Association ◽  
Rank Test ◽  
Study Cohort ◽  
Research Database ◽  
Gallbladder Stones ◽  
Log Rank Test

To evaluate the risk of colorectal cancer (CRC) after cholecystectomy for gallbladder stones (GBS). Methods: This nationwide population-based cohort study analyzed the inpatient data from the Taiwan National Health Insurance Research Database. The study cohort comprised of 83,963 patients aged ≥ 20 years undergoing cholecystectomy for GBS between 2000 and 2010. The control cohort comprised the GBS patients without cholecystectomy, who were propensity matched with the study cohort at a 1:1 ratio based on age, sex, comorbidities, and the index date for cholecystectomy. Results: The cumulative incidence of CRC within 6 months of follow-up was higher in the cholecystectomy cohort than that in the non-cholecystectomy cohort (aHR (adjusted hazard ratio) = 7.90, 95% confidence interval (CI) = 6.27–9.94; log-rank test, p < 0.001). The cumulative incidence of CRC after 6 months of follow-up was lower in the cholecystectomy cohort than that in the non-cholecystectomy cohort (aHR = 0.66, 95% CI = 0.60–0.73; log-rank test, p < 0.001), but the reduced risk of CRC for the cholecystectomy cohort was statistically significant only in rectal cancer after separately considering females (aHR = 0.64, 95% CI = 0.46–0.88) and males (aHR = 0.59, 95% CI = 0.44–0.79). Conclusions: The positive association between cholecystectomy and the CRC risk within the first 6 months after cholecystectomy might be due to a detection bias or pre-existing CRC. However, cholecystectomy is associated with a decreased risk of rectal cancer, rather than proximal or distal colon cancer, after more than 6 months of follow-up.

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.

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