Transcriptome biomarkers of colon cancer liver metastasis response to neoadjuvant triplet chemotherapy: a case series.

Abstract

Introduction: The triplet FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) may be considered an effective option in the neoadjuvant setting for metastatic colon cancer (mCRC). To investigate potential molecular criteria for treatment response, we evaluate the transcriptome of paired primary colon tumors and liver metastases.

Method: Two sets of quadruple-matched specimens (primary colon tumor, liver metastasis, normal colon and liver tissues) from five patients with resectable mCRC before and after neoadjuvant FOLFOXIRI were selected for RNA sequencing (RNA-seq).

Results: RNA-seq data showed that liver metastases exhibited a higher number of differentially expressed genes (DEGs) than colon tumors (FDR < 0.05, 301 vs. 62, respectively). Up-regulation of IL1RN, MTCO1P12, RN7SL1, ALDH1A1, DUSP1, COX1, and FOS may be associated with colon tumor sensitivity to FOLFOXIRI. HBB, GADD45B, DUSP1, FOSB, HBA2, TSC22D3, TAGLN, PER1, CSRP1, CCN2, NAMPT, ZBTB16, SERPINE1, ISG20, SRGN, ATF3, IL7R, IFITM2, and KLF2 may potentially be involved in the partial liver metastasis response. EPS8L2 was the only gene highly expressed in pre-treatment liver tissue of the complete responder patient compared to others (|Log2FC| = 3.84, FDR < 0.05).

Conclusion: Data obtained indicate transcriptional discordance between the primary tumors and liver metastases during neoadjuvant FOLFOXIRI, with the pattern of DEGs involved in their response being distinct. The EPS8L2 transcript could be regarded as a candidate biomarker of liver complete response; however, prognostic conclusions cannot be drawn from this cohort.