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Reduced expression of a gene proliferation signature is associated with enhanced malignancy in colon cancer.

Anjomshoaa A, Lin YH, Black MA, McCall JL, Humar B, Song S, Fukuzawa R, Yoon HS, Holzmann B, Friederichs J, van Rij A, Thompson-Fawcett M, Reeve AE - Br. J. Cancer (2008)

Bottom Line: Notably, we observed a significant association between reduced GPS expression and an increased likelihood of recurrence (P < 0.05), leading to shorter disease-free survival in both cohorts.This contrasts with many other carcinomas such as breast cancer.Investigating the reasons underlying this unusual observation may provide important insight into the biology of colon cancer progression and putative novel therapy options.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Cancer Genetics Laboratory, University of Otago, Dunedin, New Zealand.

ABSTRACT
The association between cell proliferation and the malignant potential of colon cancer is not well understood. Here, we evaluated this association using a colon-specific gene proliferation signature (GPS). The GPS was derived by combining gene expression data obtained from the analysis of a cancer cell line model and a published colon crypt profile. The GPS was overexpressed in both actively cycling cells in vitro and the proliferate compartment of colon crypts. K-means clustering was used to independantly stratify two cohorts of colon tumours into two groups with high and low GPS expression. Notably, we observed a significant association between reduced GPS expression and an increased likelihood of recurrence (P < 0.05), leading to shorter disease-free survival in both cohorts. This finding was not a result of methodological bias as we verified the well-established association between breast cancer malignancy and increased proliferation, by applying our GPS to public breast cancer data. In this study, we show that reduced proliferation is a biological feature characterizing the majority of aggressive colon cancers. This contrasts with many other carcinomas such as breast cancer. Investigating the reasons underlying this unusual observation may provide important insight into the biology of colon cancer progression and putative novel therapy options.

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Disease-free survival analysis of colon cancer patients stratified into high and low groups according to the GPS expression or 15 cell cycle-regulated genes included in the GPS. In both cohorts, the low GPS groups had significantly shorter DFS compared with the high GPS groups (A and C). This difference was more significant when only cell cycle-regulated genes were used to stratify patients (D and F). The same association was found when the analysis was limited to those cohort A patients who received no adjuvant therapy (B and E).
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fig2: Disease-free survival analysis of colon cancer patients stratified into high and low groups according to the GPS expression or 15 cell cycle-regulated genes included in the GPS. In both cohorts, the low GPS groups had significantly shorter DFS compared with the high GPS groups (A and C). This difference was more significant when only cell cycle-regulated genes were used to stratify patients (D and F). The same association was found when the analysis was limited to those cohort A patients who received no adjuvant therapy (B and E).

Mentions: To examine whether a difference in cell proliferation determined by the GPS may be associated with time to recurrence, DFS was plotted for low GPS and high GPS tumours (Figure 2). DFS was significantly shorter in patients with reduced GPS expression (P=0.033 and 0.011 for cohort A and B patients, respectively; Figure 2A and C). This association remained significant in cohort A, when patients with adjuvant therapy were excluded (P=0.029; Figure 2B).


Reduced expression of a gene proliferation signature is associated with enhanced malignancy in colon cancer.

Anjomshoaa A, Lin YH, Black MA, McCall JL, Humar B, Song S, Fukuzawa R, Yoon HS, Holzmann B, Friederichs J, van Rij A, Thompson-Fawcett M, Reeve AE - Br. J. Cancer (2008)

Disease-free survival analysis of colon cancer patients stratified into high and low groups according to the GPS expression or 15 cell cycle-regulated genes included in the GPS. In both cohorts, the low GPS groups had significantly shorter DFS compared with the high GPS groups (A and C). This difference was more significant when only cell cycle-regulated genes were used to stratify patients (D and F). The same association was found when the analysis was limited to those cohort A patients who received no adjuvant therapy (B and E).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2538751&req=5

fig2: Disease-free survival analysis of colon cancer patients stratified into high and low groups according to the GPS expression or 15 cell cycle-regulated genes included in the GPS. In both cohorts, the low GPS groups had significantly shorter DFS compared with the high GPS groups (A and C). This difference was more significant when only cell cycle-regulated genes were used to stratify patients (D and F). The same association was found when the analysis was limited to those cohort A patients who received no adjuvant therapy (B and E).
Mentions: To examine whether a difference in cell proliferation determined by the GPS may be associated with time to recurrence, DFS was plotted for low GPS and high GPS tumours (Figure 2). DFS was significantly shorter in patients with reduced GPS expression (P=0.033 and 0.011 for cohort A and B patients, respectively; Figure 2A and C). This association remained significant in cohort A, when patients with adjuvant therapy were excluded (P=0.029; Figure 2B).

Bottom Line: Notably, we observed a significant association between reduced GPS expression and an increased likelihood of recurrence (P < 0.05), leading to shorter disease-free survival in both cohorts.This contrasts with many other carcinomas such as breast cancer.Investigating the reasons underlying this unusual observation may provide important insight into the biology of colon cancer progression and putative novel therapy options.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Cancer Genetics Laboratory, University of Otago, Dunedin, New Zealand.

ABSTRACT
The association between cell proliferation and the malignant potential of colon cancer is not well understood. Here, we evaluated this association using a colon-specific gene proliferation signature (GPS). The GPS was derived by combining gene expression data obtained from the analysis of a cancer cell line model and a published colon crypt profile. The GPS was overexpressed in both actively cycling cells in vitro and the proliferate compartment of colon crypts. K-means clustering was used to independantly stratify two cohorts of colon tumours into two groups with high and low GPS expression. Notably, we observed a significant association between reduced GPS expression and an increased likelihood of recurrence (P < 0.05), leading to shorter disease-free survival in both cohorts. This finding was not a result of methodological bias as we verified the well-established association between breast cancer malignancy and increased proliferation, by applying our GPS to public breast cancer data. In this study, we show that reduced proliferation is a biological feature characterizing the majority of aggressive colon cancers. This contrasts with many other carcinomas such as breast cancer. Investigating the reasons underlying this unusual observation may provide important insight into the biology of colon cancer progression and putative novel therapy options.

Show MeSH
Related in: MedlinePlus