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. 2012 Sep 7:12:395.
doi: 10.1186/1471-2407-12-395.

RON is not a prognostic marker for resectable pancreatic cancer

Carole M Tactacan  1 , David K Chang, Mark J Cowley, Emily S Humphrey, Jianmin Wu, Anthony J Gill, Angela Chou, Katia Nones, Sean M Grimmond, Robert L Sutherland, Andrew V Biankin, Roger J Daly; Australian Pancreratic Genome Initiative
Collaborators, Affiliations

RON is not a prognostic marker for resectable pancreatic cancer

Carole M Tactacan et al. BMC Cancer. .

Abstract

Background: The receptor tyrosine kinase RON exhibits increased expression during pancreatic cancer progression and promotes migration, invasion and gemcitabine resistance of pancreatic cancer cells in experimental models. However, the prognostic significance of RON expression in pancreatic cancer is unknown.

Methods: RON expression was characterized in several large cohorts, including a prospective study, totaling 492 pancreatic cancer patients and relationships with patient outcome and clinico-pathologic variables were assessed.

Results: RON expression was associated with outcome in a training set, but this was not recapitulated in the validation set, nor was there any association with therapeutic responsiveness in the validation set or the prospective study.

Conclusions: Although RON is implicated in pancreatic cancer progression in experimental models, and may constitute a therapeutic target, RON expression is not associated with prognosis or therapeutic responsiveness in resected pancreatic cancer.

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Figures

Figure 1
Figure 1
Western blot of pro-RON and RON β-chain expression across a panel of pancreatic cancer cell lines. MIA PaCa-2 and Panc 10.05 are low-expressing and high-expressing controls, respectively.
Figure 2
Figure 2
Optimization of RON immunohistochemical staining. Immunohistochemical staining of RON in MIA PaCa-2 and Panc 10.05 cell lines (A and B), using IgG rabbit and anti-RON primary antibodies in pancreatic cancer tissues (C and D), and in benign ductal cells of the pancreas and in breast cancer with high RON expression (E and F), at low and high magnification. Examples of absent, low, moderate to high RON staining in pancreatic cancer tissue are also shown (G-J).
Figure 3
Figure 3
Kaplan-Meier survival curves for patients stratified based upon RON expression in the training (n = 64, with n = 51 low and n = 13 high) (A) and validation (n = 281, with n = 265 low and n = 16 high) (B) cohorts. The p-value from fitting a Cox proportional hazards model to the survival curves is indicated in the plots.
Figure 4
Figure 4
Kaplan-Meier survival curves for patients stratified according to adjuvant chemotherapy status with high RON expression (n = 16) (A) and low or absent RON expression (n = 265) (B) in the validation cohort (n = 281). The p-value from fitting a Cox proportional hazards model to the survival curves is indicated in the plots.
Figure 5
Figure 5
Kaplan-Meier survival curves for patients stratified based upon RON mRNA expression in the prospectively accrued ICGC cohort of PC (n = 88). Patients were split into two groups using a 50% low : 50% high cutoff (n = 44 in both groups) (A), or an 80% low : 20% high cutoff (n = 70 and n = 18, respectively) which matches the cutoff found using protein expression in the training cohort (B). The p-value from fitting a Cox proportional hazards model to the survival curves is indicated in the plots.
Figure 6
Figure 6
Kaplan-Meier survival curves for patients stratified based upon mRNA expression levels of MSP (A), MT-SP1 (B), a two-gene signature combination of RON + MSP expression (C), and a three-gene signature combination of RON + MSP + MT-SP1 expression (D) from the prospectively accrued ICGC cohort (n = 88). All genes use a 50%:50% low:high cutoff. The p-value from fitting a Cox proportional hazards model to the survival curves is indicated in the plots.
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References

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