Development of a clinically feasible molecular assay to predict recurrence of Dukes’ B colon cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20110-20110
Author(s):  
Y. Jiang ◽  
Y. Zhang ◽  
T. Briggs ◽  
D. Talantov ◽  
A. Mazumder ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Multivariate Analysis ◽  
Cancer Patients ◽  
Therapeutic Option ◽  
Univariate Analysis ◽  
Clinical Importance ◽  
Gene Signature ◽  
Rt Pcr ◽  
Pcr Assay ◽  
Tissue Samples

20110 Background: The 5-year survival rate of Dukes’ B colon cancer patients is approximately 75%. In our earlier genome-wide measurements of gene expression we have identified a 23-gene signature that sub-classifies Dukes’ B tumors and may provide better means of risk assessment on an individual basis for these colon cancer patients. The aim of this study is to validate this gene signature in an independent and more diverse group of patients, and further develop this prognostic signature into a clinical feasible test using formalin-fixed paraffin-embedded (FFPE) tissue samples. Methods: Using Affymetrix U133a GeneChip we analyzed the expression of the 23 genes in total RNA of frozen tumor samples from 123 Dukes’ B patients who did not receive adjuvant systemic treatment. Furthermore, we developed a quantitative RT-PCR assay for this gene signature in order to perform the test with standard clinical FFPE samples. Results: In the independent validation set of 123 patients, the gene signature proved to be informative in identifying patients who would develop distant metastasis (hazard ratio, HR 2.56; 95% confidence interval CI, 1.01–6.48), even when corrected for the traditional prognostic factors in multivariate analysis (HR, 2.73; 95% CI, 0.97–7.73). The RT-PCR assay developed for this gene signature was also validated in an independent set of 114 patients as a strong prognostic factor for the development of distant recurrence (HR, 6.38; 95% CI, 2.88–14.2) in univariate analysis and in multivariate analysis (HR, 13.3; 95% CI, 5.13–34.4). Conclusions: Our data provide not only a validation of the pre-defined prognostic gene signature for Dukes’ B colon cancer patients but also a clear feasibility of testing the gene signature using RT-PCR with standard FFPE specimens. The ability of such a test to identify patients that have an unfavorable outcome demonstrates potential clinical importance that could lead clinicians to choose a more aggressive therapeutic option for the high-risk patients. [Table: see text]

CHFR methylation as an epigenetic marker for recurrence of colon cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4043-4043
Author(s):  
M. Tanaka ◽  
S. Sethi ◽  
D. Li ◽  
G. Bland ◽  
S. R. Hamilton ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Cancer Patients ◽  
Univariate Analysis ◽  
Stage Ii ◽  
Rank Test ◽  
Tissue Samples ◽  
Epigenetic Marker

4043 Background: Currently, no definitive epigenetic markers exist to predict recurrence and overall survival (OS) of colorectal cancer patients after surgical resection. Promoter hypermethylation of the ID4 (inhibitor of DNA binding), RECK (reversion-inducing cysteine rich protein with Kazal motifs), and CHFR (checkpoint with forkhead-associated and RING finger domains) genes have been associated with reduced mRNA and protein expression in colorectal cancer. The purpose of this study was to determine the association of methylation of these genes and also MINT1 (methylated in tumor loci) with recurrence-free survival (RFS) and OS in colon cancer patients. Methods: DNA methylation was quantitatively evaluated using pyrosequencing in tissue samples from 64 patients with AJCC stage II and III colon cancer without HNPCC seen at M.D. Anderson during 1999–2007. Survival outcomes were determined by retrospective chart review and evaluated by Kaplan-Meier plot and log-rank test for univariate analysis and Cox's proportional hazard model for multivariate analysis. Mean methylation rate of multiple CpG sites in the promoter region was used. For this analysis, we defined <15%, 15%-30%, and >30% as methylation-negative, -low, and -high, respectively. Results: There were 19 stage II (30%) and 45 stage III (70%) patients. The median age was 62.1 years (range: 31–86). Adjuvant chemotherapy was completed in 49 patients (77%). After a median follow-up of 54.9 months, 12 (19%) patients developed recurrence and 7 (11%) have died. Methylation of MINT1, ID4, and RECK did not correlate with RFS and OS. The CHFR methylation-high (42%) group had low RFS (P=.04) and OS (P=.03) when compared with the CHFR methylation- negative (38%) and -low (20%) group. CHFR methylation-high was associated with N2 disease (P=.04) and right-sided tumors (P=.002). Multivariate analysis indicated T4 disease [P=.004, HR=8.42 (95% CI: 1.98–35.8)] and CHFR methylation-high [P=.04, HR = 3.79 (95% CI: 1.04–13.8)], were poor prognostic factors for recurrence. Conclusions: The presence of high CHFR promoter methylation correlates with advanced lymph node metastasis and shortened RFS and OS. Methylation of the CHFR promoter is a potential epigenetic marker for colon cancer recurrence and overall survival. No significant financial relationships to disclose.

scholarly journals Identification of Distinct Molecular Patterns and a Four-Gene Signature in Colon Cancer Based on Invasion-Related Genes

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunfei Dong ◽  
Tao Shang ◽  
HaiXin Ji ◽  
Xiukou Zhou ◽  
Zhi Chen
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Cancer Patients ◽  
Risk Group ◽  
Univariate Analysis ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Training Dataset ◽  
Lasso Regression ◽  
Independent Predictive Factor

BackgroundThe pathological stage of colon cancer cannot accurately predict recurrence, and to date, no gene expression characteristics have been demonstrated to be reliable for prognostic stratification in clinical practice, perhaps because colon cancer is a heterogeneous disease. The purpose was to establish a comprehensive molecular classification and prognostic marker for colon cancer based on invasion-related expression profiling.MethodsFrom the Gene Expression Omnibus (GEO) database, we collected two microarray datasets of colon cancer samples, and another dataset was obtained from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) further underwent univariate analysis, least absolute shrinkage, selection operator (LASSO) regression analysis, and multivariate Cox survival analysis to screen prognosis-associated feature genes, which were further verified with test datasets.ResultsTwo molecular subtypes (C1 and C2) were identified based on invasion-related genes in the colon cancer samples in TCGA training dataset, and C2 had a good prognosis. Moreover, C1 was more sensitive to immunotherapy. A total of 1,514 invasion-related genes, specifically 124 downregulated genes and 1,390 upregulated genes in C1 and C2, were identified as DEGs. A four-gene prognostic signature was identified and validated, and colon cancer patients were stratified into a high-risk group and a low-risk group. Multivariate regression analyses and a nomogram indicated that the four-gene signature developed in this study was an independent predictive factor and had a relatively good predictive capability when adjusting for other clinical factors.ConclusionThis research provided novel insights into the mechanisms underlying invasion and offered a novel biomarker of a poor prognosis in colon cancer patients.

CLINICAL SIGNIFICANCE OF SERUM CAVEOLIN-1 LEVELS IN GASTRIC CANCER PATIENTS

2018 ◽  
Vol 40 (4) ◽  
pp. 323-327 ◽  
Author(s):  
F Tas ◽  
S Karabulut ◽  
K Erturk ◽  
D Duranyildiz
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Histological Grade ◽  
Clinical Importance ◽  
Disease Stage ◽  
Control Group ◽  
Tissue Samples ◽  
Caveolin 1 ◽  
Study Results ◽  
Gastric Cancer Patients

Aim: Caveolin-1 plays a significant role in the pathogenesis of various carcinomas and its expression affects the survival of cancer patients. However, the molecular function of caveolin-1 and its possible clinical importance has remained uncertain in gastric cancer. No clinical trial has examined serum caveolin-1 levels in gastric cancer patients so far, instead all available results were provided from studies conducted on tissue samples. In the current study, we analyzed the soluble serum caveolin-1 levels in gastric cancer patients, and specified its associations with the clinical factors and prognosis. Material and Methods: Sixty-three patients with pathologically confirmed gastric cancer were enrolled into the trial. Serum caveolin-1 concentrations were detected by ELISA method. Thirty healthy subjects were also included in the study. Results: The median age of patients was 62 years, ranging from 28 to 82 years. The serum caveolin-1 levels in gastric cancer patients were significantly higher than those in control group (p < 0.001). The common clinical parameters including patient age, sex, lesion localization, histopathology, histological grade, disease stage, and various serum tumor markers (e.g. LDH, CEA, and CA 19.9) were not found to be associated with serum caveolin-1 levels (p > 0.05). Similarly, no correlation existed between serum caveolin-1 concentration and chemotherapy responsiveness (p = 0.93). Furthermore, serum caveolin-1 level was not found to have a prognostic role (p = 0.16). Conclusion: Even though it is neither predictive nor prognostic, serum caveolin-1 level may be a valuable diagnostic indicator in patients with gastric cancer. Key

scholarly journals Predictive factors of posttreatment fracture by definitive radiotherapy for uterine cervical cancer

2020 ◽  
Author(s):  
Kazuki Ishikawa ◽  
Tsuneo Yamashiro ◽  
Takuro Ariga ◽  
Takafumi Toita ◽  
Wataru Kudaka ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Risk Factors ◽  
Cervical Cancer ◽  
Multivariate Analysis ◽  
Radiation Therapy ◽  
Cancer Patients ◽  
Clinical Characteristics ◽  
Univariate Analysis ◽  
Uterine Cervical Cancer

Abstract Purpose Fractures are known to shorten life expectancy and worsen the quality of life. The risk of fractures after radiation therapy in cervical cancer patients is known to be multifactorial. In this study, we examined risk factors for fractures in cervical cancer patients, especially by evaluating bone densities and DVH parameters for fractured bones. Materials and Methods For 42 patients, clinical characteristics, pretreatment CT bone densities, and radiation dose were compared between patients with and without fractures. Results Posttreatment fractures occurred in 25 bones among ten patients. Pretreatment CT bone densities were significantly lower in patients with fractures (P < 0.05–0.01 across sites, except for the ilium and the ischium). Although DVH parameters were also significantly associated with fractures in univariate analysis, only CT densities were significantly associated with fractures in multivariate analysis. Conclusion Pretreatment CT densities of spinal and pelvic bones, which may reflect osteoporosis, have a significant impact on the risk for posttreatment fractures.

The potential of cytokeratin 20 and mucin 2 mRNA as metastasis markers in regional lymph nodes of colon cancer patients investigated by quantitative RT-PCR

2009 ◽  
Vol 24 (3) ◽  
pp. 261-268 ◽  
Author(s):  
Oddmund Nordgård ◽  
Satu Oltedal ◽  
Hartwig Kørner ◽  
Ole Gunnar Aasprong ◽  
Kjersti Tjensvoll ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Cytokeratin 20 ◽  
Rt Pcr ◽  
Regional Lymph Nodes ◽  
Mucin 2

Diagnostic and Prognostic Utility of Serum Receptor-Binding Cancer Antigen Expressed on SiSo Cells (RCAS1) Levels in Colon Cancer Patients

2009 ◽  
Vol 24 (2) ◽  
pp. 70-76 ◽  
Author(s):  
Costas Giaginis ◽  
Alexandra Margeli ◽  
Gregory Kouraklis ◽  
Athina Zira ◽  
Gerasimos Tsourouflis ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Receptor Binding ◽  
Univariate Analysis ◽  
Disease Stage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Individuals ◽  
Cancer Antigen ◽  
Cox Regression Analysis ◽  
Prognostic Utility

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a human tumor-associated antigen that induces cell-cycle arrest and/or apoptosis in cells bearing the RCAS1 receptor. The aim of the present study was to elucidate the diagnostic and prognostic utility of RCAS1 levels in colon cancer patients. Serum RCAS1 levels were determined using a sandwich enzyme-linked immunosorbent assay in 97 colon cancer patients and 20 healthy individuals. The levels were significantly increased in colon cancer patients compared to healthy individuals (p<0.0001). Increased RCAS1 levels were significantly associated with advanced Dukes’ stage (p=0.0079) and high histopathological tumor grade (p=0.0028). Univariate analysis revealed that colon cancer patients with elevated RCAS1 levels had significantly shorter overall survival times (log-rank test, p=0.027). By multivariate analysis, serum RCAS1 was identified as an independent prognostic factor (Cox regression analysis, p=0.033). In conclusion, colon cancer patients with advanced disease stage and grade and poor prognosis showed elevated serum RCAS1 levels. Assessment of serum RCAS1 levels could therefore be considered as a diagnostic and prognostic marker in colon neoplasia.

Assessment of Hematologic and Non-Hematologic Toxicity in Older Cancer Patients Receiving Systemic Chemotherapy: Results from a Prospective Nationwide Registry.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3131-3131
Author(s):  
Naeem Tahir ◽  
Jerome H. Goldschmidt ◽  
Eva Culakova ◽  
Marek S. Poniewierski ◽  
Debra A. Wolff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Cancer Patients ◽  
Performance Status ◽  
Univariate Analysis ◽  
Hematologic Toxicity ◽  
Breast Cancer Patients ◽  
Nationwide Registry ◽  
Older Cancer Patients ◽  
Grade Iii

Abstract Introduction: Although 60% of all malignancies occur in patients ≥65, this population is poorly represented in cancer clinical trials. While fit elderly patients appear to tolerate chemotherapy as well as younger individuals, less is known about chemotherapy tolerance in older cancer patients with poor performance status or co-morbidities. The purpose of this study was to examine the impact of patient and disease characteristics on the reported toxicities of cancer chemotherapy. Methods: This study represents part of a prospective, nationwide registry based at 137 randomly selected practice sites throughout the US. The major malignancies considered were cancers of the breast (33%), colon (10%), lung (19%) and ovary (7%) along with malignant lymphoma (8%). To date, 3422 patients have been registered of which 2719 are available for analysis including 1083 patients age ≥65 (40%). Primary outcome measures were: relative dose intensity (RDI) compared to standard doses, anemia (Hgb &lt;10), neutropenia (neutrophils &lt;1000) and non-hematologic toxicities pertinent to older adults including stomatitis, diarrhea, anorexia, dehydration and weight loss. Univariate and multivariate logistic regression analysis was performed to compare the difference between the 65–74 and ≥75 age groups. Results: Complete data were available on 927 patients ≥65 years of age. Among breast cancer patients, increasing age (&lt;65, 65–74, ≥75) was associated with progressively less Grade III/IV neutropenia (62%, 51% and 41%), respectively (p=0.006). This corresponds to patients receiving progressively less RDI (93.4%, 91.3%, 89.8%; P=.025) with 17%, 19% and 25% receiving RDI &lt;85%, respectively. Most of the reduced RDI was planned in patients ≥75 years compared with less than half in younger patients (P=.035). Non-breast cancer patients experienced no significant difference in rates of Grade III/IV neutropenia by age. Increasing age was associated with progressively more anemia (27%, 34%, and 44%) respectively (p&lt;0.0001) among non-breast cancer patients but not among those with breast cancer. Despite a trend, no significant increase in non-hematologic toxicities was observed with increasing age in breast cancer or non-breast cancer patients. Factors significantly associated with Grade III/IV neutropenia in univariate analysis included baseline ANC &lt;3000, BSA&lt;2.0, female gender and anthracycline containing regimens. In multivariate analysis, after adjusting for tumor type and performance status the following were significant predictors of Grade III/IV neutropenia: BSA&lt;2.0 (OR=1.5 p=0.04), Baseline ANC&lt;3000 (OR=2.0 p=0.001) and anthracycline containing regimen (OR=3.5 p&lt;0.0001). Factors associated with non-hematologic toxicity in univariate analysis included colon cancer (p&lt;0.0001), Charlson Co-morbidity Index (CCI) ≥ 3 (p=0.068), ECOG performance status ≥2 (p=0.05), and 5-Fluorouracil containing regimens (p&lt;0.0001) while in multivariate analysis, only the CCI maintained a trend towards increased non-hematologic toxicity (p=0.069). Conclusions: While anemia increases with age in non-breast cancer patients, neutropenia decreases with increasing age in breast cancer patients, most likely as a result of age-related reductions in RDI.

Development and validation of a robust prognostic and predictive signature for colorectal cancer (CRC) patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4036-4036
Author(s):  
A. M. Glas ◽  
P. Roepman ◽  
R. Salazar ◽  
G. Capella ◽  
V. Moreno ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Gene Signature ◽  
Low Risk ◽  
Stage Ii ◽  
Significant Difference ◽  
Independent Cohort

4036 Background: Between 25 and 35% of stage II CRC patients will experience a recurrence of their disease and may benefit from adjuvant chemotherapy. Official guidelines give suggestions but no clear recommendation for best risk stratification. Here we describe the development a robust signature that predicts disease relapse and can assist in treatment decisions. Methods: Fresh frozen tumor tissues from 180 patients with stage I, II and III colorectal cancer undergoing surgery were analyzed using high density Agilent 44K oligonucleotide arrays. Median FU was 70.2 months; 85% of patients did not receive adjuvant chemotherapy. Unsupervised hierarchical clustering based on full-genome gene expression measurement indicated the existence of 3 main colon molecular subclasses. Survival analysis of the 3 classes showed that subtype C (n= 27) had a poor outcome and subtype A (n= 48) good outcome. Only the intermediate group B (n=104) was used to develop a signature by using a cross validation procedure to score all genes for their association with 5-yr distant metastasis free survival (DMFS) and subsequently applied to all samples (n=180). The obtained gene signature was further validated on an independent cohort of 178 stage II + III colon samples. Results: A set of 38 prognosis related gene probes showed robust DMFS association in over 50% of all iterations in the Training Set of 180 samples. The gene signature was validated on an independent cohort of 178 samples from stage II + III colon cancer patients. The profile classified 61% of the validation samples as low-risk and 39% as high-risk. The low- and high-risk samples showed a significant difference in DMFS with a HR of 3.19 (P= 8.5e-4). Five-year DMFS rates were 89% (95%CI 83–95) for low-risk and 62% (95%CI 50–77) for high-risk samples. Moreover, the profile showed a significant performance within stage II (P=0.0058) and III (P=0.036) only samples. The performance of the profile was significant for both untreated (P=0.0082) and treated patients (P=0.016) suggesting that its power is independent of treatment benefits. Conclusions: ColoPrint is able to predict the prognosis of stage II and III colon cancer patients and facilitates the identification of patients who would benefit from adjuvant chemotherapy. [Table: see text]

Outcome of colon cancer patients with synchronous metastases

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4029-4029
Author(s):  
I. Sobhani ◽  
F. Roudot-Thoraval ◽  
F. Mesli ◽  
B. Landi ◽  
T. Aparicio ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Cox Model ◽  
Univariate Analysis ◽  
Colon Surgery ◽  
Teaching Hospitals ◽  
Rank Test ◽  
Metastatic Colon Cancer ◽  
Curative Surgery ◽  
Synchronous Metastases

4029 Background: Metastatic colon cancer patients may undergo chemotherapy without colon surgery. However, the outcome of patients has not been evaluated and antiagiogenic agents can not be given. The aim of the present cohort study was to analyse factors influencing patients’ survival. Methods: Consecutive patients [N=228, mean age (sd) 64 (12) yrs, median follow-up 20 mths;84 females] treated in 6 teaching hospitals received chemotherapy for metastatic colonic cancer, either as the first step, or after surgery. Progressive free survival (PFS) was estimated using Kaplan-Meïer method. Factors associated with PFS were tested by means of Log rank test and results are presented in terms of medians of survival (95% CI). Factors independently related to PFS were tested using a Cox model and results are presented as hazard ratio. Results: 105 patients with colon cancer and synchronous metastatsis underwent colon surgery prior to chemotherapy (68 males, mean age 64 yrs) when 123 patients were treated first by chemotherapy ± biotherapy (76 males, mean age 63 yrs). By univariate analysis, following factors were significantly associated with PFS: surgery first 25.5 (18.6 - 32.5) vs chemotherapy first 18.3 (14.7 - 21.9) mths p = 0.006; curative surgery: yes 35.7 (29.6 - 41.8) vs no 18.4 (15.6 - 21.2) mths p < 0.001; tumour histological differentiation : no : 13.4 (6.2 - 20.6) vs well : 24.7 (20.4 - 29.1) mths p<0.001; synchronous metastases: liver only 25.5 (20.5 - 30.6) vs peritonea&nodes : 18.4 (10.6 - 26.1) vs pulmonary & other sites : 16.5 (14.7 - 18.3) mths p < 0.0001; need for colonic stent: yes 16.4 (9.3 - 23.5) vs no 23.9 (21.1 - 26.7) months p < 0.0001; antiangiogenic drug: yes 36.6 (28.7 - 44.5) vs no : 20.7 (18.3 - 23.1) p = 0.033. After Cox multivariate analysis five independent factors were found to be associated with PFS. Conclusions: Colon surgery before chemotherapy plus bevacizumab appears to be the more appropriate choice, and associated with longer PFS, especially for those patients with well differentiated tumours and synchronous liver metastases. [Table: see text] No significant financial relationships to disclose.

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