Alterations in the transcriptional factor c-MYC could be involved in the anti-EGFR resistance in metastatic colorectal cancer (mCRC). The c-MYC expression was evaluated in 121 RAS and BRAF wild-type mCRC before treatment with anti-EGFR+Folfiri therapy and in 33 subsequent metastases collected during target therapy (TT) or in TT resistance phase. We analyzed the expression and the functional role of some c-MYC linked miRNAs (miR-31-3p, miR-143 and miR-145) in our patient group and in two CRC cell lines, also performing a c-MYC target PCR array. Patients with higher c-MYC expression (HME) showed a significant lower PFS and OS when compared to those with low c-MYC expression (LME). HME pattern was significantly more frequent in the metastases after TT and significantly associated to anti-EGFR molecular resistance alterations. We also found a significant correlation between the expression of the above-mentioned c-MYC linked miRNAs, c-MYC level and anti-EGFR resistance. Moreover, expression gene profiling pointed out the pivotal role of c-MYC in CRC-related cell-cycle, apoptosis, signal transduction and cell-growth pathways. c-MYC expression might distinguish patients with a lower PFS and OS in anti-EGFR treated mCRC. The individuation of some miRNAs involved in the c-MYC pathway regulation and the downstream c-MYC effector genes could provide a new possible target to overcome the anti-EGFR resistance in mCRC.

Strippoli, A., Cocomazzi, A., Basso, M., Cenci, T., Ricci, R., Pierconti, F., Cassano, A., Fiorentino, V., Barone, C. A., Bria, E., Ricci-Vitiani, L., Tortora, G., Larocca, L. M., Martini, M., C-myc expression is a possible keystone in the colorectal cancer resistance to egfr inhibitors, <<CANCERS>>, 2020; 12 (3): 638-656. [doi:10.3390/cancers12030638] [http://hdl.handle.net/10807/153450]

C-myc expression is a possible keystone in the colorectal cancer resistance to egfr inhibitors

Strippoli, Antonia
Primo
;
Cocomazzi, Alessandra;Basso, Michele;Cenci, Tonia;Ricci, Riccardo;Pierconti, Francesco;Cassano, Alessandra;Fiorentino, Vincenzo;Barone, Carlo Antonio;Bria, Emilio;Tortora, Giampaolo;Larocca, Luigi Maria;Martini, Maurizio
Ultimo
2020

Abstract

Alterations in the transcriptional factor c-MYC could be involved in the anti-EGFR resistance in metastatic colorectal cancer (mCRC). The c-MYC expression was evaluated in 121 RAS and BRAF wild-type mCRC before treatment with anti-EGFR+Folfiri therapy and in 33 subsequent metastases collected during target therapy (TT) or in TT resistance phase. We analyzed the expression and the functional role of some c-MYC linked miRNAs (miR-31-3p, miR-143 and miR-145) in our patient group and in two CRC cell lines, also performing a c-MYC target PCR array. Patients with higher c-MYC expression (HME) showed a significant lower PFS and OS when compared to those with low c-MYC expression (LME). HME pattern was significantly more frequent in the metastases after TT and significantly associated to anti-EGFR molecular resistance alterations. We also found a significant correlation between the expression of the above-mentioned c-MYC linked miRNAs, c-MYC level and anti-EGFR resistance. Moreover, expression gene profiling pointed out the pivotal role of c-MYC in CRC-related cell-cycle, apoptosis, signal transduction and cell-growth pathways. c-MYC expression might distinguish patients with a lower PFS and OS in anti-EGFR treated mCRC. The individuation of some miRNAs involved in the c-MYC pathway regulation and the downstream c-MYC effector genes could provide a new possible target to overcome the anti-EGFR resistance in mCRC.
2020
Inglese
Strippoli, A., Cocomazzi, A., Basso, M., Cenci, T., Ricci, R., Pierconti, F., Cassano, A., Fiorentino, V., Barone, C. A., Bria, E., Ricci-Vitiani, L., Tortora, G., Larocca, L. M., Martini, M., C-myc expression is a possible keystone in the colorectal cancer resistance to egfr inhibitors, <<CANCERS>>, 2020; 12 (3): 638-656. [doi:10.3390/cancers12030638] [http://hdl.handle.net/10807/153450]
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