Tumor cancer stem cell genetic profile as predictor of relapse in stage II and III radically resected colon cancer patients.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 429-429
Author(s):  
Riccardo Giampieri ◽  
Mario Scartozzi ◽  
Cristian Loretelli ◽  
Alessandra Mandolesi ◽  
Alessandro Bittoni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Patients ◽  
Stage Ii ◽  
Genetic Profile ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Group A ◽  
Colorectal Cancer Patients ◽  
Risk Of Relapse

429 Background: Although disease stage is the most relevant factor influencing treatment choice in locally advanced radically resected colon cancer, it is not uncommon to observe disease relapse in patients with apparent low risk stage that are usually excluded from an adjuvant therapy. On the contrary we also know that some patients with high risk stage are not likely to relapse, independently from medical treatment received. Preclinical data suggested that cancer stem cells may influence the biological behaviour of many solid tumours including colorectal cancer, we then tested a panel of genetic markers of stemness in resected Dukes stage B and C colorectal cancer patients in order to define a prognostic profile. Methods: We performed k-means unsupervised clustering (K=2) using the mRNA expression data of 66 genes. The algorithm divided the patients into two groups (A and B). Most patients clustered in a manner consistent with relapse free survival, defined as the time between primary surgery and first radiological sign of metastatic involvement or patients death, whichever came first. Results: A total of 62 patients were analysed (36, 58% stage II and 26, 41% stage III), 36 (58%) patients relapsed during the follow-up period (range 1.63-86.5 months). Respectively 12 (19%) and 50 (81%) patients were allocated into group A and B. A significantly different median relapse-free survival was observed between the 2 groups (22.18 vs 42.85 months, p=0.0296). Interestingly, even if group A had a worse outcome in terms of risk of relapse, an higher proportion of stage II patients could be found in this group (83%) when compared with the group B (52%). Among tested genes, those with the highest capability in determining allocation into one of the two groups were CD44, ALCAM, DTX2, HSPA9, CCNA2, PDX1, MYST1, COL1A1 and ABCG2. Conclusions: This analysis supports the idea that, other than (or maybe more than) stage, biological variables, such as expression levels of colon cancer stem cell genes, may be relevant in determining an increased risk of relapse in resected colorectal cancer patients. Our findings may also be relevant for new treatment strategies targeting tumour stem cells genetic profile.

scholarly journals P-0197 Common VEGF Gene Polymorphisms are Not Associated With Relapse-Free Survival in Colorectal Cancer Patients

2012 ◽  
Vol 23 ◽  
pp. iv86-iv87
Author(s):  
Guenter Hofmann ◽  
Tanja Langsenlehner ◽  
Florentine Moazedi-Fuerst ◽  
Armin Gerger ◽  
Sonja Kielhauser ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Gene Polymorphisms ◽  
Vegf Gene ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Colorectal Cancer Patients

Adjuvant treatment in extreme elderly patients with colorectal cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 784-784
Author(s):  
Marta Llopis Cuquerella ◽  
Maria del Carmen Ors Castaño ◽  
María Ballester Espinosa ◽  
Alejandra Magdaleno Cremades ◽  
Vicente Boix Aracil ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Elderly Patients ◽  
Cancer Patients ◽  
Adjuvant Treatment ◽  
Stage Ii ◽  
Stage Iii ◽  
Complementary Treatment ◽  
Colorectal Cancer Patients

784 Background: Surgical and adjuvant treatment in extreme elderly ( > 80 years) patients with localized colorectal cancer is an unresolved issue. Owing to the lack of available neither clinical practice nor investigational data in this field we present our experience in this scenario. Methods: We retrospectively reviewed data regarding surgical and complementary treatment for colorectal cancer patients aged more than 80 consecutively attended by General Surgery Department in Vega Baja Hospital between 2008 and 2013. Results: A total number of 115 colorectal cancer patients were registered. 95 patients diagnosed of localized disease were selected for analysis. Colon vs rectal cancer ratio was 4:1. Median age was 83.6 years (80-94). Male sex was predominant (60 patients, 63.2%). Emergency surgery was performed in 15 patients (15.8%). Complementary treatment to surgery was advised, according to international guidelines, in 53 patients (55.8%). 10 patients (18.9%) with an advise of adjuvant treatment finally received it. More patients with rectal cancer received recommended treatment (41.7% rectal vs 12.2% colon cancer). Patients with stage III disease were more frequently finally treated according to guidelines (22.2 % stage III vs 11.8% stage II). More patients with stage II rectal cancer were advised and received treatment (recommendation: 66.7% rectal vs 36.1% colon cancer; administration: 25% rectal vs 7.7% colon cancer). Treatment was also more frequently administered to stage III rectal cancer (50% rectal vs 14.3% rectal cancer) (Table). Conclusions: Our experience in localized colorectal cancer in extreme elderly patients ( > 80 years) showed that, although advised according to guidelines, most of them did not receive adjuvant treatment to surgery. Complementary treatment administration was more common in rectal cancer patients and with more advanced disease. [Table: see text]

scholarly journals A SMAD4-modulated gene profile predicts disease-free survival in stage II and III colorectal cancer

2020 ◽  
Author(s):  
Bryan C. Szeglin ◽  
Chao Wu ◽  
Michael R. Marco ◽  
Hyun Sung Park ◽  
Zeda Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Training Dataset ◽  
Validation Dataset ◽  
Gene Profile ◽  
Free Survival ◽  
Colorectal Cancer Patients ◽  
Disease Free

AbstractObjectiveLoss of SMAD4 is associated with worse outcomes for colorectal cancer patients. We used gene ontology and bioinformatics to identify an RNA-based SMAD4-modulated profile and test its association with patient outcome.DesignUsing a discovery dataset of 250 colorectal cancer patients, we analyzed expression of BMP/Wnt target genes for association with SMAD4 expression. Promoters of the BMP/Wnt genes were interrogated for SMAD-binding elements. 15 genes were implicated and three tested for modulation by SMAD4 in patient-derived colorectal cancer tumoroids. Expression of the 15 genes was used for unsupervised hierarchical clustering of a training dataset and two resulting clusters modeled in a centroid model. This model was applied to an independent validation dataset of stage II and III patients. Disease-free survival was analyzed by the Kaplan-Meier method.ResultsIn vitro analysis of three genes identified in the SMAD4-modulated profile (JAG1, TCF7, MYC) revealed modulation by SMAD4 consistent with the trend observed in the profile. In the training dataset (n = 553), the profile was not associated with outcome. However, among stage II and III patients (n = 461), distinct clusters were identified by unsupervised hierarchical clustering that were associated with disease-free survival (p = 0.02). The main model was applied to a validation dataset (n = 257) which confirmed the association of clustering with disease-free survival (p = 0.02).ConclusionsA SMAD4-modulated RNA-based gene profile identified high-risk stage II and III colorectal cancer patients, can predict disease-free survival, and has prognostic potential for stage II and III colorectal cancer patients.

Prognostic effects of circulating markers of epithelial mesenchymal transition (EMT) in metastatic colorectal cancer patients.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 456-456
Author(s):  
Neeraj Nailesh Shah ◽  
Christopher Hanyoung Lieu ◽  
Cristina Ivan ◽  
Michael J. Overman ◽  
Masayoshi Shimizu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Overall Survival ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Plasma Samples ◽  
Free Survival ◽  
Circulating Markers ◽  
Colorectal Cancer Patients ◽  
Circulating Levels

456 Background: EMT is a phenotypic description of cancer cells that include loss of cell adhesion, increased motility, invasion, and chemoresistance. EMT gene signature is a poor prognostic feature in colon cancer. Circulating markers to decipher the EMT signature in colorectal cancer patients (CRC pts) would therefore be of clinical relevance. Studies have shown that miR-21, IL-6 and IL-8 have been associated with EMT in cancer cells in vitro and their expression has been shown to be highly correlated in primary colon cancer tissue Methods: Plasma samples were obtained from two mCRC cohorts: 120 pts with unresectable metastases, and 91 pts who subsequently underwent partial hepatectomy with curative intent. Circulating levels of IL-6, IL-8 and miR-21 (normalized by miR-16) were measured, and dichotomized using previously published cutoffs. Pts with high levels of ≥2 of 3 EMT markers were categorized as having an EMT phenotype. Survival analysis was by log-rank and proportional hazard. Results: As previously seen in colon tissue, miR-21, IL-6 and IL-8 expression were correlated in plasma samples (P<0.001) and individually associated with shorter overall survival (P<0.05). The EMT phenotype, present in 44% of both cohorts, was a strong predictor of poor overall survival in the unresectable cohort (HR 2.6, 95% CI 1.6 to 4.1, median OS 15.5 mo v 27.1 mo, P<0.001) as well as in the validation resectable cohort(HR 3.8, 95% CI 1.9 to 7.7, median OS 41.5 mo vs 81.9 mo, P<0.001). This effect was sustained in a multivariate analysis after adjustment for tumor volume and clinical characteristics (HR 1.92, P=0.009 in unresectable cohort and HR 3.53, p=0.002 in hepatectomy cohort). The EMT phenotype was also predictive of shorter progression-free survival (HR 2.2, 15.8 mo vs 7.8 mo, P=0.02) and relapse-free survival (HR 2.1, 18.4 mo vs 31.4 mo, P=0.01) in the two respective cohorts, consistent with prior preclinical data correlating EMT with chemoresistance Conclusions: As surrogates of EMT, circulating levels of miR-21, IL-6 and IL-8 are co-expressed in plasma of mCRC pts and can be used to predict overall survival and benefit from chemotherapy. This finding highlights the clinical relevance of EMT in colon cancer biology

scholarly journals Non‐invasive metastasis prognosis from plasma metabolites in stage II colorectal cancer patients: The DACHS study

2019 ◽  
Vol 145 (1) ◽  
pp. 221-231 ◽  
Author(s):  
Inna Zaimenko ◽  
Carsten Jaeger ◽  
Hermann Brenner ◽  
Jenny Chang‐Claude ◽  
Michael Hoffmeister ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Stage Ii ◽  
Plasma Metabolites ◽  
Non Invasive ◽  
Stage Ii Colorectal Cancer ◽  
Colorectal Cancer Patients

Preoperative Vascular Endothelial Growth Factor Levels as a Prognostic Marker for Stage II or III Colorectal Cancer Patients

2011 ◽  
Vol 4 ◽  
pp. CGM.S7113 ◽  
Author(s):  
Ozgur Kemik ◽  
Ahu Sarbay Kemik ◽  
Aziz Sümer ◽  
Sevim Purisa ◽  
A. Cumhur Dulger ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cancer Patients ◽  
Elevated Serum ◽  
Stage Ii ◽  
Vascular Endothelial ◽  
Poor Survival ◽  
Colorectal Cancer Patients ◽  
Endothelial Growth Factor

Background The aim of the present study was to determine whether serum vascular endothelial growth factor (VEGF) can provide prognostic information independent of carcinoembryonic antigen levels in patients undergoing curative surgery. Methods Serum samples were collected from 158 patients with colorectal cancer and from 100 controls. Serum and tissue levels of VEGF were measured by enzyme-linked immunosorbent assay. Serum VEGF levels in colorectal cancer patients were compared with those in healthy controls, and we retrospectively assessed the association between serum VEGF levels and clinicopathologic findings and survival. Results VEGF expression was significantly higher in colorectal cancer tissue compared with nontumor tissue. Mean serum VEGF levels in patients were significantly higher than those in controls, and significantly higher in patients with large tumors, lymph node involvement, and distant metastases. Conclusion Elevated serum VEGF was significantly associated with poor survival, but was only an independent risk factor for poor survival in Stage II and/or III disease. Elevated serum VEGF is significantly associated with development of colorectal cancer, and lymph or distant invasive phenotypes and survival, especially in Stage II and III patients.

scholarly journals PIK3CAandTP53mutations predict overall survival of stage II/III colorectal cancer patients

2018 ◽  
Vol 24 (5) ◽  
pp. 631-640 ◽  
Author(s):  
A-Jian Li ◽  
Hua-Guang Li ◽  
Er-Jiang Tang ◽  
Wei Wu ◽  
Ying Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Stage Ii ◽  
Colorectal Cancer Patients
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