mRNA expression profiles of colorectal liver metastases as a novel biomarker for early recurrence after partial hepatectomy

Abstract

SurgeryBiomarker mRNA Prognostic value A B S T R A C TBackground: Identification of specific risk groups for recurrence after surgery for isolated colorectal liver metastases (CRLM) remains challenging due to the heterogeneity of the disease. Classical clinicopathologic parameters have limited prognostic value. The aim of this study was to identify a gene expression signature measured in CRLM discriminating early from late recurrence after partial hepatectomy. Methods: CRLM from two patient groups were collected: I) with recurrent disease 12 months after surgery (N ¼ 33), and II) without recurrences and disease free for !36 months (N ¼ 30). The patients were clinically homogeneous; all had a low clinical risk score (0e2) and did not receive (neo-) adjuvant chemotherapy. Total RNA was hybridised to Illumina arrays, and processed for analysis. A leave-one-out cross validation (LOOCV) analysis was performed to identify a prognostic gene expression signature. Results: LOOCV yielded an 11-gene profile with prognostic value in relation to recurrent disease 12 months after partial hepatectomy. This signature had a sensitivity of 81.8%, with a specificity of 66.7% for predicting recurrences ( 12 months) versus no recurrences for at least 36 months after surgery (X 2 P < 0.0001). Conclusion:The current study yielded an 11-gene signature at mRNA level in CRLM discriminating early from late or no relapse after partial hepatectomy.

Recurrence‐associated gene signature optimizes recurrence‐free survival prediction of colorectal cancer

“…A test approved by the US Food and Drug Administration (MammaPrint; Agendia, Amsterdam, the Netherlands) has been successfully developed for prognostic prediction in breast cancer (Glas et al, 2006;van 't Veer et al, 2002). Several gene signatures have also been established to distinguish the prognosis of patients beyond the CRC clinicopathological features; however, most of them are not used clinically (Agesen et al, 2012;Jensen et al, 2015;O'Connell et al, 2010;Oh et al, 2012;Schell et al, 2016;van der Stok et al, 2016). Thus, identifying a more powerful and practical gene signature for prognosis prediction is of great clinical significance.…”

B Cells as Prognostic Biomarker After Surgery for Colorectal Liver Metastases

“…The inclusion criteria for patients were also very different between studies. Our study and that of van der Stok et al (11) did not administer neoadjuvant or adjuvant chemotherapy to included patients, while the three other studies did (9,10,12). Neoadjuvant chemotherapy influences tumour biology and might thereby alter gene expression levels (38).…”

“…The top differentially expressed genes in the tumour samples in this study did not overlap with those of the four previously published expression signatures (9-12). However, no individual gene was shared between these earlier studies either (9)(10)(11)(12). This may partly be explained by the different experimental methods used by the studies.…”

“…This may partly be explained by the different experimental methods used by the studies. We used mRNA sequencing, while the earlier studies used different expression microarrays (9)(10)(11)(12)37). The inclusion criteria for patients were also very different between studies.…”

“…Recent advances in technology have led to the notion that molecular characteristics might outperform clinicopathological scoring systems in predicting patient treatment and survival (8). Four individual centres have published prognostic gene signatures for colorectal liver metastases based on expression microarrays, but no single gene was shared between the four signatures (9)(10)(11)(12).…”