Technically 35 are up, two special elections, and only 22 are Republican seats so we could afford to lose 2 of the 35 with the goal of removing Trump. Still doable.
We could, however, lose 9 of them and still undo citizens united, pass medicaid for all, maybe tax the rich, etc.
More realistically I think we will see Republicans getting ousted in different ways than electing the DNC whose platform are those reforms I mentioned, instead we will probably see their seats go to moderate independents.