New Study: Genes associated with hypoxia ... and .. liver cancer prognosis

[Guest guest]

Good morning,

In this new study, the researchers hypothesized that in primary liver

cancer (hepatocellular carcinoma) certain microenvironmental regions exist with

a characteristic gene expression related to chronic hypoxia (low oxygen)

which will induce aggressive behavior.

Indeed, a 7-gene set was found in liver cancer that was associated with

chronic hypoxia.

This 7-gene set associated with hypoxia correlates with a bad prognosis -

early recurrence and poor survival.

THOUGHTS: Once again, the importance of oxygen!

Sally

_Clin Cancer Res._ (javascript:AL_get(this, 'jour', 'Clin Cancer Res.')

2010 Jun 30. [Epub ahead of print]

A 7 Gene Set Associated with Chronic Hypoxia of Prognostic Importance in

Hepatocellular Carcinoma.

_van Malenstein H_

(http://preview.ncbi.nlm.nih.gov/pubmed?term= " van%20Malenstein%20H " [Author]) ,

_Gevaert O_

(http://preview.ncbi.nlm.nih.gov/pubmed?term= " Gevaert%20O " [Author]) , _Libbrecht

L_

(http://preview.ncbi.nlm.nih.gov/pubmed?term= " Libbrecht%20L " [Author]) , _Daemen

A_

(http://preview.ncbi.nlm.nih.gov/pubmed?term= " Daemen%20A " [Author]) ,

_Allemeersch J_

(http://preview.ncbi.nlm.nih.gov/pubmed?term= " Allemeersch%20J " [Author]) ,

_Nevens F_

(http://preview.ncbi.nlm.nih.gov/pubmed?term= " Nevens%20F " [Author]) , _Van Cutsem

E_

(http://preview.ncbi.nlm.nih.gov/pubmed?term= " Van%20Cutsem%20E " [Author]) ,

_Cassiman D_

(http://preview.ncbi.nlm.nih.gov/pubmed?term= " Cassiman%20D " [Author]) , _De Moor

B_

(http://preview.ncbi.nlm.nih.gov/pubmed?term= " De%20Moor%20B " [Author]) ,

_Verslype C_

(http://preview.ncbi.nlm.nih.gov/pubmed?term= " Verslype%20C " [Author]) , _van Pelt

J_

(http://preview.ncbi.nlm.nih.gov/pubmed?term= " van%20Pelt%20J " [Author]) .

Hepatology, University Hospital Gasthuisberg.

Abstract

PURPOSE: Hepatocellular carcinomas (HCC) have an unpredictable clinical

course and molecular classification can provide better insight in prognosis

and patient directed therapy. We hypothesized that in HCC certain

microenvironmental regions exist with a characteristic gene expression related

to

chronic hypoxia which will induce aggressive behavior.EXPERIMENTAL DESIGN: We

determined the gene expression pattern for human HepG2 liver cells under

chronic hypoxia by microarray. Differentially expressed genes were selected

and their clinical value was assessed. In our hypothesis-driven analysis we

included available independent microarray studies of patients with HCC in

one single analysis. Three microarray studies encompassing 272 patients were

used as training sets to determine a minimal prognostic gene set and one

recent study of 91 patients was used for validation. RESULTS: Using

computational methods we identified 7 genes, out of 3592 differentially

expressed

under chronic hypoxia, that showed correlation with poor prognostic

indicators in all training sets (65/139/73 patients) and this was validated in

a 4th

dataset (91 patients). Retrospectively the 7-gene set is associated with

poor survival (HR 1.39, p=0.007) and early recurrence (HR 2.92, p=0.007) in

135 patients. Moreover, using a hypoxia score based on this 7-gene set we

found that patients with a score >0.35 (n=42) had a median survival of 307

days, whereas patients with a score </=0.35 (n=93) had a median survival of

1602 days (p=0.005).CONCLUSIONS: We identified a unique, liver specific

7-gene signature associated with chronic hypoxia that correlates with poor

prognosis in HCCs.