Limits...
A 19-Gene expression signature as a predictor of survival in colorectal cancer

View Article: PubMed Central - PubMed

ABSTRACT

Background: Histopathological assessment has a low potential to predict clinical outcome in patients with the same stage of colorectal cancer. More specific and sensitive biomarkers to determine patients’ survival are needed. We aimed to determine gene expression signatures as reliable prognostic marker that could predict survival of colorectal cancer patients with Dukes’ B and C.

Methods: We examined microarray gene expression profiles of 78 archived tissues of patients with Dukes’ B and C using the Illumina DASL assay. The gene expression data were analyzed using the GeneSpring software and R programming.

Results: The outliers were detected and replaced with randomly chosen genes from the 90 % confidence interval of the robust mean for each group. We performed three statistical methods (SAM, LIMMA and t-test) to identify significant genes. There were 19 significant common genes identified from microarray data that have been permutated 100 times namely NOTCH2, ITPRIP, FRMD6, GFRA4, OSBPL9, CPXCR1, SORCS2, PDC, C12orf66, SLC38A9, OR10H5, TRIP13, MRPL52, DUSP21, BRCA1, ELTD1, SPG7, LASS6 and DUOX2. This 19-gene signature was able to significantly predict the survival of patients with colorectal cancer compared to the conventional Dukes’ classification in both training and test sets (p < 0.05). The performance of this signature was further validated as a significant independent predictor of survival using patient cohorts from Australia (n = 185), USA (n = 114), Denmark (n = 37) and Norway (n = 95) (p < 0.05). Validation using quantitative PCR confirmed similar expression pattern for the six selected genes.

Conclusion: Profiling of these 19 genes may provide a more accurate method to predict survival of patients with colorectal cancer and assist in identifying patients who require more intensive treatment.

Electronic supplementary material: The online version of this article (doi:10.1186/s12920-016-0218-1) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus

a Cancerous tissue section of patients Dukes' B well-differentiated adenocarcinoma. Hematoxylin (purple) stains chromatin in the nucleus and eosin (pink orangish) gives color to the protein that resides in the cytoplasm of muscle cells. Tumor cells appear to thicken and be seen spreading muscular propia but did not penetrate serous layer. b. Well differentiated adenocarcinoma Dukes’ C tissue section invaded into muscular propia and involved lymph nodes
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC5016995&req=5

Fig1: a Cancerous tissue section of patients Dukes' B well-differentiated adenocarcinoma. Hematoxylin (purple) stains chromatin in the nucleus and eosin (pink orangish) gives color to the protein that resides in the cytoplasm of muscle cells. Tumor cells appear to thicken and be seen spreading muscular propia but did not penetrate serous layer. b. Well differentiated adenocarcinoma Dukes’ C tissue section invaded into muscular propia and involved lymph nodes

Mentions: Clinical and pathological features of 78 patients were separated into poor and good survival groups of patients who survived less than five years and more than five years respectively. In this study, the 5 year survival rate among patients of Dukes’ B was 59.5 % while Dukes’ C was 36.5 %. It was in concordance to the United State data [4]. The differences in clinical parameters between Dukes’ B and C patients were not statistically significant (Fisher’s exact test p = 0.173) (Table 1). Kaplan Meier curves were constructed based on Dukes’ staging and the survival time showed no statistically significant difference (log rank p = 0.242, data not shown). Fig. 1 showed the H&E staining results of patient Dukes’ B and C.Table 1


A 19-Gene expression signature as a predictor of survival in colorectal cancer
a Cancerous tissue section of patients Dukes' B well-differentiated adenocarcinoma. Hematoxylin (purple) stains chromatin in the nucleus and eosin (pink orangish) gives color to the protein that resides in the cytoplasm of muscle cells. Tumor cells appear to thicken and be seen spreading muscular propia but did not penetrate serous layer. b. Well differentiated adenocarcinoma Dukes’ C tissue section invaded into muscular propia and involved lymph nodes
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5016995&req=5

Fig1: a Cancerous tissue section of patients Dukes' B well-differentiated adenocarcinoma. Hematoxylin (purple) stains chromatin in the nucleus and eosin (pink orangish) gives color to the protein that resides in the cytoplasm of muscle cells. Tumor cells appear to thicken and be seen spreading muscular propia but did not penetrate serous layer. b. Well differentiated adenocarcinoma Dukes’ C tissue section invaded into muscular propia and involved lymph nodes
Mentions: Clinical and pathological features of 78 patients were separated into poor and good survival groups of patients who survived less than five years and more than five years respectively. In this study, the 5 year survival rate among patients of Dukes’ B was 59.5 % while Dukes’ C was 36.5 %. It was in concordance to the United State data [4]. The differences in clinical parameters between Dukes’ B and C patients were not statistically significant (Fisher’s exact test p = 0.173) (Table 1). Kaplan Meier curves were constructed based on Dukes’ staging and the survival time showed no statistically significant difference (log rank p = 0.242, data not shown). Fig. 1 showed the H&E staining results of patient Dukes’ B and C.Table 1

View Article: PubMed Central - PubMed

ABSTRACT

Background: Histopathological assessment has a low potential to predict clinical outcome in patients with the same stage of colorectal cancer. More specific and sensitive biomarkers to determine patients’ survival are needed. We aimed to determine gene expression signatures as reliable prognostic marker that could predict survival of colorectal cancer patients with Dukes’ B and C.

Methods: We examined microarray gene expression profiles of 78 archived tissues of patients with Dukes’ B and C using the Illumina DASL assay. The gene expression data were analyzed using the GeneSpring software and R programming.

Results: The outliers were detected and replaced with randomly chosen genes from the 90 % confidence interval of the robust mean for each group. We performed three statistical methods (SAM, LIMMA and t-test) to identify significant genes. There were 19 significant common genes identified from microarray data that have been permutated 100 times namely NOTCH2, ITPRIP, FRMD6, GFRA4, OSBPL9, CPXCR1, SORCS2, PDC, C12orf66, SLC38A9, OR10H5, TRIP13, MRPL52, DUSP21, BRCA1, ELTD1, SPG7, LASS6 and DUOX2. This 19-gene signature was able to significantly predict the survival of patients with colorectal cancer compared to the conventional Dukes’ classification in both training and test sets (p < 0.05). The performance of this signature was further validated as a significant independent predictor of survival using patient cohorts from Australia (n = 185), USA (n = 114), Denmark (n = 37) and Norway (n = 95) (p < 0.05). Validation using quantitative PCR confirmed similar expression pattern for the six selected genes.

Conclusion: Profiling of these 19 genes may provide a more accurate method to predict survival of patients with colorectal cancer and assist in identifying patients who require more intensive treatment.

Electronic supplementary material: The online version of this article (doi:10.1186/s12920-016-0218-1) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus