Screening of Pleural Mesotheliomas for DNA-damage Repair Players by Digital Gene Expression Analysis Can Enhance Clinical Management of Patients Receiving Platin-Based Chemotherapy.

BACKGROUND

Malignant pleural mesothelioma (MPM) is a rare, predominantly asbestos-related and biologically highly aggressive tumour leading to a dismal prognosis. Multimodality therapy consisting of platinum-based chemotherapy is the treatment of choice. The reasons for the rather poor efficacy of platinum compounds remain largely unknown.

MATERIAL AND METHODS

For this exploratory mRNA study, 24 FFPE tumour specimens were screened by digital gene expression analysis. Based on data from preliminary experiments and recent literature, a total of 366 mRNAs were investigated using a Custom CodeSet from NanoString. All statistical analyses were calculated with the R i386 statistical programming environment.

RESULTS

and gene expression were correlated with lymph node spread, and expression levels with higher IMIG stage. and expression was associated with TNM stage. as well as expression levels were correlated with tumour progression in the overall cohort of patients. and gene expression influenced overall survival in this collective. In the adjuvant treated cohort only, , as well as were significantly associated with overall survival. Furthermore, expression was associated with progression in this subgroup.

CONCLUSION

DNA-damage response plays a crucial role in response to platin-based chemotherapeutic regimes. In particular, , and are strongly associated with tumour progression. , and most promising are prognostic markers for OS in MPM. , , and seem to be also predictive markers in adjuvant treated MPMs. After a prospective validation, these markers may improve clinical and pathological practice, finally leading to a patients' benefit by an enhanced clinical management.