The Comparable Microenvironment Shared by Colorectal Adenoma and Carcinoma: An Evidence of Stromal Proteomics

Tumor microenvironment (TME) is a key factor involved in cancer development and metastasis. In the TME of colorectal cancer (CRC), the gene expression status of stromal tissues could influence the CRC process from normal to adenoma then carcinoma; however, the expression status at the protein level has not yet been well evaluated. A total of 22 CRC patients were recruited for this study, and the tissue regions corresponding with adjacent, adenoma, and carcinoma were carefully excised by laser capture microdissection (LCM), including a patient with adenoma and carcinoma. The individual proteomes of this cohort were implemented by high-resolution mass spectrometer under data-independent acquisition (DIA) mode. A series of informatic analysis was employed to statistically seek the proteomic characteristics related with the stroma at different stages of CRC. The identified proteins in the colorectal stromal tissues were much less than and almost overlapped with that in the corresponding epithelial tissues; however, the patterns of protein abundance in the stroma were very distinct from those in the epithelium. Although qualitative and quantitative analysis delineated the epithelial proteins specifically typified in the adjacent, adenoma, and carcinoma, the informatics in the stroma led to another deduction that such proteomes were only divided into two patterns, adjacent- and adenoma/carcinoma-dependent. The comparable proteomes of colorectal adenoma and carcinoma were further confirmed by the bulk preparation- or individual LCM-proteomics. The biochemical features of the tumor stromal proteomes were characterized as enrichment of CD4+ and CD8+ T cells, upregulated pathways of antigen presentation, and enhancement of immune signal interactions. Finally, the features of lymphoid lineages in tumor stroma were verified by tissue microarray (TMA). Based on the proteomic evidence, a hypothesis was raised that in the colorectal tissue, the TME of adenoma and carcinoma were comparable, whereas the key elements driving an epithelium from benign to malignant were likely decided by the changes of genomic mutations or/and expression within it.

Automated summary

The tumor microenvironment plays a crucial role in cancer development and metastasis. In colorectal cancer, the protein expression status of the stromal tissues significantly impacts the progression from normal to adenoma and carcinoma. However, the evaluation of protein expression at the stromal level is still limited. This study recruited 22 CRC patients and used laser capture microdissection and mass spectrometry to analyze the proteomic characteristics at different stages of CRC. The results revealed distinctive protein abundance patterns between the stroma and epithelial tissues, indicating the importance of stromal proteins in CRC development. The biochemical features of the tumor stromal proteomes were characterized by the enrichment of T cells, upregulated antigen presentation pathways, and enhanced immune signal interactions. Tissue microarray analysis further confirmed the presence of lymphoid lineages in the tumor stroma. Based on these findings, a hypothesis was proposed that the TME of adenoma and carcinoma in colorectal tissue are comparable, while the transition from benign to malignant epithelium is likely driven by changes in genomic mutations or/and expression.