You can run interpolation ("Analysis: Math: Interpolate/Extrapolate" menu) for both Y datasets with same X range and number of points so that the two results have the identical X datasets. Then you can calculate the difference between one interpolated Y and the other interpolated Y. (If you want to plot the difference, you can show the X datasets by choosing "Column: Show X Column" menu, and turning ON the "Clear Sampling Interval" checkbox on the 1st interpolated Y dataset.)
I'm not sure the significance part because you have only 2 observations at each X, though possible to test.