High CLS is associated with more aggressive tumor characteristics and treatment resistance. TP53, CSMD1, and RB1 mutations are more frequent in high CLS samples, which also show more amplifications and deletions. High CLS patients are more sensitive to 5-fluorouracil, gemcitabine, and doxorubicin, while low CLS patients respond better to immunotherapy. Here, CSMD1 is linked to neoplasm.