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

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

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

Authors:

Walter RF, Vollbrecht C, Werner R, Mairinger T, Schmeller J, Flom E, Wohlschlaeger J, Barbetakis N, Paliouras D, Chatzinikolaou F, Adamidis V, Tsakiridis K, Zarogoulidis P, Trakada G, Christoph DC, Schmid KW, Mairinger FD

Abstract

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:

CDC25A and PARP1 gene expression were correlated with lymph node spread, BRCA1 and TP73 expression levels with higher IMIG stage. NTHL1 and XRCC3 expression was associated with TNM stage. CHECK1 as well as XRCC2 expression levels were correlated with tumour progression in the overall cohort of patients. CDKN2A and MLH1 gene expression influenced overall survival in this collective. In the adjuvant treated cohort only, CDKN2ACHEK1 as well as ERCC1 were significantly associated with overall survival. Furthermore, TP73expression was associated with progression in this subgroup.

CONCLUSION:

DNA-damage response plays a crucial role in response to platin-based chemotherapeutic regimes. In particular, CHEK1XRCC2 and TP73 are strongly associated with tumour progression. ERCC1, MLH1CDKN2A and most promising CHEK1 are prognostic markers for OS in MPM. TP73CDKN2ACHEK1 and ERCC1 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.

KEYWORDS:

DNA-damage repair; NanoString nCounter; digital gene expression analysis; platin-based chemotherapy.; pleural mesothelioma

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2018-07-05T11:24:59+00:00 4 Νοεμβρίου 2016|Για Ιατρούς|