B Cells as Prognostic Biomarker After Surgery for Colorectal Liver Metastases

Abstract

Background: The aim of this study was to identify more accurate variables to improve prognostication of individual patients with colorectal liver metastases (CRLM). Clinicopathological characteristics only partly explain the large range in survival rates. Methods: MessengerRNA expression profiles of resected CRLM of two patient groups were analysed by mRNA sequencing: poor survivors (death from recurrent disease <30 months after surgery) and good survivors (no recurrent disease >60 months after surgery). Tumour and adjacent liver parenchyma samples were analysed. Results: MessengerRNA expression profiling of the tumour samples identified 77 genes that were differentially expressed between the two survival groups at a False Discovery Rate (FDR) <0.1. In the adjacent liver parenchyma samples only one gene, MTRNR2L1, showed significantly higher expression in the good survivors. Pathway analysis showed higher expression of immune-related and stroma-related genes in tumour samples from good survivors. Expression data was then validated by immunohistochemistry in two cohorts comprising a total of 125 patients. Immunohistochemical markers that showed to be associated with good survival in the total cohort were: high K/L+ infiltration in tumour stroma [p = 0.029; OR 2.500 (95% CI 1.100-5.682)] and high CD79A+ infiltration in tumour stroma [p = 0.036; OR 2.428 (95%CI 1.062-5.552)]. Conclusions: A high stromal infiltration of CD79A+ B cells and K/L+ plasma cells might be favourable prognostic biomarkers after surgery for CRLM.

Keywords: B cells; RNA sequencing; cancer; colorectal liver metastases; genetics; immunohistochemistry.

Figure 1

Heatmap of tumour samples. Unsupervised clustering of the 77 genes with the lowest FDR values in DESeq2 analysis. Samples are shown on the x-axis and the 77 genes on the y-axis. A quantile colour scale is used with 10 different colours ranging from black (low expression) to yellow (high expression).

Figure 2

Detailed pictures of immunohistochemistry. (A) x10 magnification image of high Kappa/Lambda + staining in the tumour stroma. Kappa light chains are stained brown, Lambda light chains are stained pink. (B) x4 magnification image of high CD79A+ staining (brown) in the invasive margin. (C) x10 magnification image of a replacement growth pattern by H&E staining. (D) x10 magnification image of a desmoplastic growth pattern by Masson's trichrome staining. Tumour and liver cells are stained purple, connective tissue (desmoplastic rim) is stained blue. Tu, tumour; Li, liver; St, tumour stroma.