The top five networking up- and downregulated DEGs (NDUFA2, SDHD, LSM5, DCAF4, COX10, RBM8A, TIMP1, QKI, TGOLN2, and PTGS2) were differently expressed in the majority of the irinotecan-resistant variants of the CRC cell lines and often presented a reversed tendency from that observed in vivo. The gene discussed is PTGS2; the disease is colorectal carcinoma.