Integrative Omics Analysis Reveals the Potential Value of CEACAM6 in Pan‐Gastrointestinal Cancers

TL;DR

This study explores how CEACAM6, a cell adhesion molecule, is overexpressed in various gastrointestinal cancers and may influence tumor growth and immune response.

Contribution

The study is the first to investigate CEACAM6's role in pan-gastrointestinal cancers using multi-omics data and spatial transcriptomics.

Findings

CEACAM6 is overexpressed in pan-gastrointestinal cancers and is linked to poor survival and immune-excluded tumor subtypes.

CEACAM6 expression is negatively correlated with CD4+ Th1 cells and plasma cells in the tumor microenvironment.

Spatial transcriptomics shows CEACAM6 is highly expressed in malignant regions and correlates with tumor progression.

Abstract

Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) is known as a cell adhesion receptor which could regulate proliferation and other signaling in cancer. The role of CEACAM6 in pan‐gastrointestinal cancers remains largely uncharacterized. This study employed multi‐omics bioinformatics to investigate the expression distribution, prognostic value, and immune function of CEACAM6 in these malignancies.

Utilizing multi‐omics data from The Cancer Genome Atlas (TCGA), cBioPortal, GDSC2, TIMER2.0, and TISCH databases, we assessed the CEACAM6 expression and prognostic value across pan‐gastrointestinal cancers. Additionally, the potential role of CEACAM6 in the tumor immune microenvironment was explored using multi‐omics data, including spatial transcriptomics data.

Based on TCGA data, CEACAM6 was found to be overexpressed in pan‐gastrointestinal cancers. The CEACAM6 somatic copy number alterations, DNA methylation and mutation sites were identified as potential contributors to abnormal CEACAM6 expression. The CEACAM6 expression was significantly negatively associated with the abundance of CD4 + Th1 cells across pan‐gastrointestinal cancers. Furthermore, spatial transcriptomics data revealed that CEACAM6 expression was significant positively associated with malignant cells, while there was a negative correlation was observed with between CEACAM6 expression and plasma cells.

CEACAM6 exhibits high diagnostic accuracy and tumor‐specific overexpression in pan‐gastrointestinal cancers. CEACAM6 could promote angiogenesis/metastasis and suppress anti‐tumor immunity. Spatially localized in tumors with immune cell exclusion, CEACAM6 correlates with poor survival and immune‐excluded subtypes, positioning it as a therapeutic target in precision immunotherapy for pan‐gastrointestinal cancers.

Expression of CEACAM6 in spatial transcriptomic of colorectal cancer with liver metastases. (A) Predicted cell types mapping on colorectal cancer tissue slice; (B) Spatial distribution of CEACAM6; (C) Spatial distribution of malignant region, mixed region and normal region; (D) The difference expression of CEACAM6 in malignant region, mixed region and normal region; (E) The correlation heatmap between CEACAM6 expression and different cell types.

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