Thymosin β4 and β10 are highly expressed at the deep infiltrative margins of colorectal cancer - A mass spectrometry analysis

OBJECTIVE: Colorectal cancer (CRC) is a complicated tumor, involving several oncogenic signaling pathways, and with a molecular mechanism not fully understood yet. The implication of thymosin beta 4 (T beta 4) with tumor insurgence and in migration of CRC cells was evidenced in the past with different methodologies, while T beta 10 connection with CRC has been sporadically investigated. This study focused on the implication of both types of thymosin in CRC progression and invasion by analyzing the changes in their levels according to different zones of the tumor, and to Dukes stage and budding index.PATIENTS AND METHODS: T beta 4 and T beta 10 were analyzed in deep and superficial tumor samples, and normal mucosa from 18 patients. Concentrations of T beta 4 and T beta 10 have been measured by high-pressure liquid chromatography (HPLC) coupled to electrospray-ion trap mass spectrometry (ESI-IT-MS). MS data were compared by Meet and ANOVA statistical analysis. Identification of thymosin and their proteoforms has been performed by HPLC-high resolution-ESI-IT-MSMS.RESULTS: Both T beta 4 and T beta 10, exhibited intra-t umoral quantitative differences, being upregulated in the deep part of the CRC. They exhibited, moreover, strong association with the Dukes stage and the budding grade, being more concentrated in patients at Dukes stage B and with budding index "2".CONCLUSIONS: The results obtained in the present investigation encouraged the hypothesis that the two thymosin are involved in colorectal cancer progression, and in promoting cancer invasion. Thus, they are good candidates to be diagnostic/prognostic biomarkers and therapy targets.