TY - JOUR
T1 - C-myc expression is a possible keystone in the colorectal cancer resistance to egfr inhibitors
AU - Strippoli, A.
AU - Cocomazzi, A.
AU - Basso, M.
AU - Cenci, T.
AU - Ricci, Riccardo
AU - Pierconti, Francesco
AU - Cassano, Alessandra
AU - Fiorentino, V.
AU - Barone, C.
AU - Bria, Emilio
AU - Ricci-Vitiani, L.
AU - Tortora, Giampaolo
AU - Larocca, L. M.
AU - Martini, M.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - C-MYC
KW - Colorectal cancer
KW - EGFR inhibitor resistance
KW - Targeted therapy
KW - C-MYC
KW - Colorectal cancer
KW - EGFR inhibitor resistance
KW - Targeted therapy
UR - https://publicatt.unicatt.it/handle/10807/153450
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85082194454&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85082194454&origin=inward
U2 - 10.3390/cancers12030638
DO - 10.3390/cancers12030638
M3 - Article
SN - 2072-6694
VL - 12
SP - 638
EP - 656
JO - Cancers
JF - Cancers
IS - 3
ER -