Basic—Alimentary TractBiomolecular Network Reconstruction Identifies T-Cell Homing Factors Associated With Survival in Colorectal Cancer
Section snippets
Patients and Database
The records of CRC patients who underwent a primary resection of their tumor at the Laennec George Pompidou European Hospital (HEGP) Hospitals between 1996 and 2004 were reviewed and described previously.18 Histopathologic and clinical findings were scored according to the International Union Against Cancer (UICC)-TNM staging system. For details, see the Supplementary Materials and Methods section and Supplementary Table 1. A secure web-based database Tumor Microenvironment Database (TME.db)
Immune-Related Genes Are Associated With the Absence of Tumor Recurrence
We first investigated gene expression in colorectal tumors. We determined the median cut-off values for each gene, and performed survival analysis for up to 10 years after primary tumor resection. Log-rank P values associated with disease-free survival then were calculated and hazard ratios were illustrated by the size of each node in a network (Figure 1). The expression of genes associated with tumor invasion (CEACAM1, CD97), metastasis spreading (ACE, EBAG9, MMP7), tumor anti-apoptotic
Discussion
The staggering complexity of multifactorial diseases such as cancer poses significant challenges for the development of stratified or personalized therapies. The integrated analysis of diverse datasets might circumvent these challenges and provide an enhanced understanding of complex systems, such as the tumor microenvironment. We applied such an integrated approach and performed global analyses of the phenome (large-scale flow cytometry experiments), transcriptome, tissue microarrays of
Acknowledgments
The authors are grateful to Dr Ion Gresser and Dr John Nelson for providing helpful comments and critical review of the manuscript.
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Conflicts of interest The authors disclose no conflicts.
Funding This work was supported by grants from the Association pour la Recherche sur le Cancer, the National Cancer Institute, the Canceropole Ile de France, Ville de Paris, INSERM, the Austrian Federal Ministry of Science and Research (Genome Programme Austria [GEN-AU] project Bioinformatics Integration Network), the Austrian Science Fund (SpezialForschungBereich [SFB] project Lipotoxicity), and the European Commission (Seventh Framework Programme [7FP], Geninca Consortium, grant number 202230).