Primary tumour immune response and lymph node yields in colon cancer

Nikhil Lal,Louis Vermeulen,Minn E Ng,Simon James Alexander Buczacki,Dedrick Kok Hong Chan

doi:10.1038/s41416-022-01700-1

Abstract

BackgroundThe mechanism underlying improved survival in non-metastatic colon cancer with higher lymph node (LN) yield is unknown. This study aimed to identify whether molecular features in the primary tumour were predictive of LN yield.MethodsClinical, genomic, transcriptomic, proteomic and methylation data of non-metastatic, colon cancers studied in The Cancer Genome Atlas were interrogated for associations with LN yield. Based on maximal survival effects, patients were segregated into high (>15) and low (≤15) LN yield. Gene set enrichment analysis was performed on transcriptomic changes to identify biological processes associated with LN yield. Correlations were validated in an independent set of Stage II colon cancers.ResultsHigh LN yield was found predictive of overall and disease-free survival. There was no association of higher LN yield and increasing nodal positivity. High LN yield was strongly linked with gene expression changes associated with the adaptive and dendritic cell immune response. This association was most prominent in node-negative cancers. Analogous findings were reproduced in the validation dataset.ConclusionThe study shows a strong association of an activated immune response in tumours with a high LN yield. Immunogenic tumours have a better prognosis, likely explaining the survival benefit with higher LN yields.

Highlights

Lymph node (LN) yield in colon cancer resections is considered crucial for adequate staging and guiding adjuvant treatment [1]
High lymph node (LN) yield in colon cancer surgery is positively associated with survival (TCGA) Colorectal (COAD) data were filtered to include all nonmetastatic, chemotherapy naive, node-negative and node-positive colon cancer resections (n = 377) [20]
KM estimates were generated using a 15 LN cut-off for both groups and an overall survival benefit of high LN yield was found in both (Fig. 3a, b)

Summary

Introduction

Lymph node (LN) yield in colon cancer resections is considered crucial for adequate staging and guiding adjuvant treatment [1]. Traditional Halstedian views propose that removal of involved LNs prevents further spread of the disease from these deposits [8] This view, cannot directly explain the clear survival benefit of high LN counts seen in the node-negative disease. Known as the Will Rogers phenomenon, may explain the survival benefit seen in node-negative disease with high LN yields [10]. The mechanism underlying improved survival in non-metastatic colon cancer with higher lymph node (LN) yield is unknown. High LN yield was strongly linked with gene expression changes associated with the adaptive and dendritic cell immune response. This association was most prominent in node-negative cancers.

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Conclusion