TFAP2E methylation status and prognosis of patients with radically resected colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3628-3628
Author(s):  
Seong Joon Park ◽  
Seung-mi Kim ◽  
Yong Sang Hong ◽  
Jae-Lyun Lee ◽  
Jeong-Eun Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Methylation Status ◽  
Stage I ◽  
Gene Encoding ◽  
Free Survival ◽  
Factors Affecting ◽  
Distal Location ◽  
Resected Stage ◽  
Significant Factors

3628 Background: Transcription factor AP-2ε, a member of the AP-2 family has extensively studied in many cancers. Recently, it has been suggested that the gene encoding AP-2ε (TFAP2E) is involved in the development of colorectal cancer (CRC) and is also associated with clinical outcomes of the patients with CRCs. Therefore, we have investigated the clinical significance of TFAP2E in CRC patients who underwent curative resections. Methods: A single-institution cohort of 248 patients with curatively resected, stage I/II/III CRCs between March and December, 2004 were included, and the analyses were performed in 193 patients whose tumors were available for TFAP2E methylation status Results: One hundred twelve patients (58%) showed TFAP2E hypermethylation, which was significantly more common in CRCs with distal location, low pathologic T stage (T1/T2) and stage I. After a median follow-up duration of 86.3 months, the patients with TFAP2E hypermethylation had a trend for better survival outcome in terms of relapse-free survival (RFS) and overall survival (OS) (TFAP2E hypermethylation vs. hypomethylation; 5-year RFS rate 90% vs. 80%, p=0.063; 6-year OS rate 88% vs. 80%, p=0.083). Multivariate analysis showed pathologic nodal stage and TFAP2E methylation status were independent prognostic factors affecting both RFS and OS, which also remained significant factors in the subgroup analysis including 154 patients with stage II/III CRCs who had received adjuvant chemotherapy. Conclusions: TFAP2E hypermethylation was associated with better clinical outcome and may be considered as an independent prognostic factor in the patients with curatively resected CRC.

Surveillance with Serial Serum Carcinoembryonic Levels Detect Colorectal Cancer Recurrences in Patients who are Initial Nonsecretors

2010 ◽  
Vol 76 (10) ◽  
pp. 1100-1103 ◽  
Author(s):  
Alicia Holt ◽  
Rebecca A. Nelson ◽  
Lily Lai
Keyword(s):  
Colorectal Cancer ◽  
Carcinoembryonic Antigen ◽  
Retrospective Review ◽  
Stage I ◽  
Recurrent Colorectal Cancer ◽  
Serum Carcinoembryonic Antigen ◽  
Serial Serum ◽  
Resected Stage ◽  
Initial Resection

Serum carcinoembryonic antigen (CEA) levels, elevated in a subgroup of patients with colorectal cancer (CRC) at presentation, are serially followed as part of recommended surveillance after initial resection. The value of following serial CEA levels in patients who initially present with less than or normal levels of CEA (nonsecretors) is controversial. This study sought to determine the use of follow-up CEA levels in nonsecretors. A retrospective review was performed of patients with resected Stage I, II, and III CRC. We excluded patients who did not have a pretreatment CEA level, at least two follow-up CEA levels, or in whom CEA levels did not normalize after resection. The patients were grouped by initial CEA values: CEA 5 ng/mL or less (nonsecretors) and CEA 5 + ng/mL: (secretors). We identified 186 patients with CRC; 146 were initial nonsecretors. We identified 22 patients with recurrent colorectal cancer; 6 were secretors and 16 patients were nonsecretors. In the secretors group, CEA was elevated with recurrence in four (66%) of the patients. In the nonsecretors, CEA was elevated with recurrence in eight (50%) of the patients. In summary, many recurrences of CRC are marked by an elevation of CEA regardless of whether the patients initially presented as secretors or nonsecretors.

scholarly journals A Novel Prognostic DNA Methylation Panel for Colorectal Cancer

2019 ◽  
Vol 20 (19) ◽  
pp. 4672 ◽  
Author(s):  
Hsin-Hua Chung ◽  
Chih-Chi Kuo ◽  
Cheng-Wen Hsiao ◽  
Chao-Yang Chen ◽  
Je-Ming Hu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Zinc Finger Protein ◽  
Methylation Status ◽  
Disease Free Survival ◽  
Stage I ◽  
Molecular Heterogeneity ◽  
Gene Methylation ◽  
Free Survival ◽  
Disease Free

Colorectal cancer (CRC) is one of the most common cancers and the second leading cause of cancer-related deaths. Discrepancies in clinical outcomes are observed even among patients with same-stage CRC due to molecular heterogeneity. Thus, biomarkers for predicting prognosis in CRC patients are urgently needed. We previously demonstrated that stage II CRC patients with NKX6.1 methylation had poor 5-year overall survival. However, the methylation frequency of NKX6.1 was only 23% in 151 pairs of CRC tissues. Thus, we aimed to develop a more robust prognostic panel for CRC using NKX6.1 in combination with three genes: LIM homeobox transcription factor 1α (LMX1A), sex-determining region Y-box 1 (SOX1), and zinc finger protein 177 (ZNF177). Through quantitative methylation analysis, we found that LMX1A, SOX1, and ZNF177 were hypermethylated in CRC tissues. LMX1A methylation was significantly associated with poor 5-year overall, and disease-free survivals in stage I and II CRC patients. Sensitivity and specificity analyses of the four-gene combination revealed the best sensitivity and optimal specificity. Moreover, patients with the four-gene methylation profile exhibited poorer disease-free survival than those without methylation. A significant effect of the four-gene methylation status on overall survival and disease-free survival was observed in early stage I and II CRC patients (p = 0.0016 and p = 0.0230, respectively). Taken together, these results demonstrate that the combination of the methylation statuses of NKX6.1, LMX1A, SOX1, and ZNF177 creates a novel prognostic panel that could be considered a molecular marker for outcomes in CRC patients.

scholarly journals Factors Affecting the Control of Chronic Rhinosinusitis With Nasal Polyps: A Comparison in Patients With or Without NERD

2021 ◽  
Vol 12 ◽  
pp. 215265672110038
Author(s):  
Markus Jukka Lilja ◽  
Anni Koskinen ◽  
Paula Virkkula ◽  
Seija Inkeri Vento ◽  
Jyri Myller ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Female Gender ◽  
Sinus Surgery ◽  
Logrank Test ◽  
Free Survival ◽  
Factors Affecting ◽  
Advanced Therapy ◽  
And Gender

Objectives The aim was to compare the control of chronic rhinosinusitis with nasal polyps (CRSwNP) after endoscopic sinus surgery (ESS), in patients with/without nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NERD). Study Desing: A retrospective hospital-based sample of CRSwNP patients with/without NERD with follow-up. Setting Tertiary rhinology centers. Methods Electronic patient record data from 116 CRSwNP patients (46 with NERD and 70 without NERD) undergoing ESS during 2001–17 were studied. Mean follow-up time was 9.9 years (range 1.1–15.3). Endpoints reflecting uncontrolled CRSwNP were revision ESS, and need for rescue/advanced therapy (e.g. antibiotics, oral corticosteroids and/or biological therapy) during follow-up. NERD was variable of interest and gender, age, asthma, allergic rhinitis (AR), smoking, Lund-Mackay (LM) score of sinus computed tomography scans previous ESS and baseline total ethmoidectomy were used as covariates. Results Twenty-one (49.7%) NERD patients and 18 (25.7%) non-NERD patients underwent revision ESS within a mean ± SD of 4.3 ± 2.8 and 3.7 ± 2.6 years, respectively (p = .013, by Logrank test). In Cox´s regression models, NERD, female gender, young age, asthma, AR, previous ESS, and lack of total ethmoidectomy were associated with revision-ESS. In adjusted model, only the total ethmoidectomy predicted revision-free survival. In adjusted logistic regression model, there was an insignificant trend that NERD and LM score were associated with the need for rescue/advanced therapy in the follow-up. Conclusions Patients with NERD had higher risk of uncontrolled CRSwNP than patient group without NERD, as measured by revision ESS and/or need for rescue/advanced therapy in the follow-up. In addition, baseline total ethmoidectomy was associated with revision-free survival.

scholarly journals TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Sha Zhou ◽  
Jianhong Peng ◽  
Liuniu Xiao ◽  
Caixia Zhou ◽  
Yujing Fang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Free Survival ◽  
Epigenetic Regulator ◽  
Crc Management ◽  
Disease Free ◽  
Resistance To Chemotherapy

AbstractResistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice.

308 Indirect treatment comparison of nivolumab versus placebo as adjuvant treatment for melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A335-A335
Author(s):  
Jeffrey Weber ◽  
Paolo Ascierto ◽  
Mark Middleton ◽  
Delphine Hennicken ◽  
Roberto Zoffoli ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Lower Risk ◽  
Phase 3 ◽  
Free Survival ◽  
Intention To Treat ◽  
Risk Of Death ◽  
Link Type ◽  
Indirect Treatment ◽  
Resected Stage

BackgroundWe have previously performed indirect treatment comparisons (ITCs) to demonstrate improvements in recurrence-free survival (RFS) and distant metastasis-free survival with nivolumab versus placebo as adjuvant treatment for resected melanoma; however, overall survival (OS) data were not available at the time. Recently, results of the phase 3 CheckMate 238 trial in patients with resected stage IIIB–IIIC/IV melanoma (American Joint Committee on Cancer [AJCC], 7th edition) showed no statistically significant difference in OS between nivolumab and ipilimumab; however, OS events were fewer than expected. In the phase 3 EORTC 18071 trial in patients with resected stage IIIA–IIIC melanoma (AJCC, 6th edition), OS was improved with ipilimumab versus placebo. Here, we provide an update on RFS and an analysis of OS in ITCs of nivolumab and placebo using data from these 2 trials with a common comparator arm: ipilimumab 10 mg/kg.MethodsITCs of nivolumab versus placebo were conducted using 4-year minimum follow-up data from CheckMate 238 (NCT02388906) and 5.3-year median follow-up data from EORTC 18071 (NCT00636168). Bucher ITCs were performed to estimate RFS and OS in the intention-to-treat populations. A sensitivity analysis of OS adjusting for subsequent therapy options was conducted in 2 steps: (1) after controlling for possible confounders and assuming that the only difference was the effect of different subsequent therapies, postrecurrence survival was compared between the 2 ipilimumab arms in each study, and (2) after adjusting for differences in postrecurrence survival, ITCs of nivolumab versus adjusted placebo were performed.ResultsIn these ITC analyses, RFS and OS results with nivolumab suggested an improvement compared with placebo. In the intention-to-treat population, nivolumab was associated with a lower risk of recurrence or death (RFS HR, 0.55; 95% CI, 0.43–0.70) and a lower risk of death (OS HR, 0.62; 95% CI, 0.44–0.88) than placebo. In the sensitivity analysis, a 63% average increase in postrecurrence survival benefit was estimated with ipilimumab in CheckMate 238 compared with ipilimumab in EORTC 18071. After adjusting for this increase in both the ipilimumab and placebo arms in EORTC 18071, nivolumab was associated with a lower risk of death than placebo (OS HR, 0.65; 95% CI, 0.45–0.91), similar to the unadjusted analysis.ConclusionsDespite the changing treatment landscape and the increased number of therapeutic options for metastatic melanoma, these ITCs suggested clinically meaningful improvement in RFS and OS with adjuvant nivolumab compared with a wait-and-watch strategy in high-risk patients with resected melanoma.AcknowledgementsWriting and editorial assistance were provided by Kakoli Parai, PhD, and Andrea Lockett of Ashfield Healthcare Communications, funded by Bristol-Myers Squibb Company.Trial RegistrationNCT02388906 (CheckMate 238), NCT00636168 (EORTC 18071)

scholarly journals Low value of whole-body dual-modality [18f]fluorodeoxyglucose positron emission tomography/computed tomography in primary staging of stage I–II nasopharyngeal carcinoma: a nest case-control study

2021 ◽  
Author(s):  
Bei-Bei Xiao ◽  
Qiu-Yan Chen ◽  
Xue-Song Sun ◽  
Ji-Bin Li ◽  
Dong-hua Luo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Stage I ◽  
Relapse Free Survival ◽  
Retropharyngeal Lymph Node ◽  
Free Survival ◽  
Pet Ct ◽  
Pre Treatment

Abstract Objectives The value of using PET/CT for staging of stage I–II NPC remains unclear. Hence, we aimed to investigate the survival benefit of PET/CT for staging of early-stage NPC before radical therapy. Methods A total of 1003 patients with pathologically confirmed NPC of stages I–II were consecutively enrolled. Among them, 218 patients underwent both PET/CT and conventional workup ([CWU], head-and-neck MRI, chest radiograph, liver ultrasound, bone scintigraphy) before treatment. The remaining 785 patients only underwent CWU. The standard of truth (SOT) for lymph node metastasis was defined by the change of size according to follow-up MRI. The diagnostic efficacies were compared in 218 patients who underwent both PET/CT and CWU. After covariate adjustment using propensity scoring, a cohort of 872 patients (218 with and 654 without pre-treatment PET/CT) was included. The primary outcome was overall survival based on intention to treat. Results Retropharyngeal lymph nodes were metastatic based on follow-up MRI in 79 cases. PET/CT was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions (72.2% [62.3–82.1] vs. 91.1% [84.8–97.4], p = 0.004). Neck lymph nodes were metastatic in 89 cases and PET/CT was more sensitive than MRI (96.6% [92.8–100.0] vs. 76.4% [67.6–85.2], p < 0.001). In the survival analyses, there was no association between pre-treatment PET/CT use and improved overall survival, progression-free survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival. Conclusions This study showed PET/CT is of little value for staging of stage I–II NPC patients at initial imaging. Key Points • PET/CT was more sensitive than MRI in detecting neck lymph node lesions whereas it was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions. • No association existed between pre-treatment PET/CT use and improved survival in stage I–II NPC patients.

Radiofrequency Ablation of Hepatic Metastases from Colorectal Cancer: Are Newer Generation Probes Better?

2006 ◽  
Vol 72 (10) ◽  
pp. 875-879 ◽  
Author(s):  
Aziz Ahmad ◽  
Steven L. Chen ◽  
Maihgan A. Kavanagh ◽  
David P. Allegra ◽  
Anton J. Bilchik
Keyword(s):  
Colorectal Cancer ◽  
Radiofrequency Ablation ◽  
First Generation ◽  
Hepatic Metastases ◽  
Disease Free Survival ◽  
Cancer Center ◽  
Free Survival ◽  
Alive With Disease ◽  
Disease Free

Second-generation radiofrequency ablation (RFA) probes and their successors have more power, shorter ablation times, and an increased area of ablation compared with the first-generation probes used before 2000. We examined whether the use of the newer probes has improved the clinical outcome of RFA for hepatic metastases of colorectal cancer at our tertiary cancer center. Of 160 patients who underwent RFA between 1997 and 2003, 52 had metastases confined to the liver: 21 patients underwent 46 ablations with the first-generation probes and 31 patients underwent 58 ablations with the newer probes. The two groups had similar demographic characteristics. At a median follow-up of 26.2 months, patients treated with the newer probes had a longer median disease-free survival (16 months vs 8 months, P < 0.01) and a lower rate of margin recurrence (5.2% vs 17.4%); eight patients had no evidence of disease and one patient was alive with disease. By contrast, of the 46 patients treated with the first-generation probes, 2 patients had no evidence of disease and 1 patient was alive with disease. Newer-generation probes are associated with lower rates of margin recurrence and higher rates of disease-free survival after RFA of hepatic metastases from colorectal cancer.

scholarly journals Combination of CDX2 expression and T stage improves prognostic prediction of colorectal cancer

2019 ◽  
Vol 47 (5) ◽  
pp. 1829-1842 ◽  
Author(s):  
Weimin Xu ◽  
Yilian Zhu ◽  
Wei Shen ◽  
Wenjun Ding ◽  
Tingyu Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Hazard Ratio ◽  
Free Survival ◽  
T Stage ◽  
Cdx2 Expression ◽  
Prognostic Prediction ◽  
Disease Free

Objective Prognostic prediction of colorectal cancer (CRC) remains challenging because of its heterogeneity. Aberrant expression of caudal-type homeobox transcription factor 2 (CDX2) is strongly correlated with the prognosis of CRC. Methods Tissue samples of patients with CRC who underwent surgery in Xinhua Hospital (Shanghai, China) from January 2010 to January 2013 were collected. CDX2 expression was semiquantitatively evaluated via immunohistochemistry. Results In total, 138 patients were enrolled in this study from a prospectively maintained institutional cancer database. The median follow-up duration was 57.5 months (interquartile range, 17.0–71.0 months). In the Cox proportional hazards model, low CDX2 expression combined with stage T4 CRC was significantly the worst prognostic factor for disease-free survival (hazard ratio = 7.020, 95% confidence interval = 3.922–12.564) and overall survival (hazard ratio = 5.176, 95% CI = 3.237–10.091). In the Kaplan–Meier survival analysis, patients with low CDX2 expression and stage T4 CRC showed significantly worse disease-free survival and overall survival than those with low CDX2 expression alone. Conclusion CDX2 expression combined with the T stage was more accurate for predicting the prognosis of CRC. Determining the prognosis of CRC using more than one variable is valuable in developing appropriate treatment and follow-up strategies.

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