Expression and clinical significance of negative costimulatory molecules B7-H1, B7-H3 and B7-H4 in the process of colorectal cancer’s evolution

Abstract

Background: We made investigations on the expression of negative costimulatory molecules B7-H1, B7-H3, B7-H4 in lesions at various stages of human colorectal cancer (CRC) evolution. We also analyzed the relevance between its expression in CRC and pathological factors in clinic and patient survival time.We finally made a result that we can ensure the clinical significance of B7-H3, B7-H4 expression and the relationship between the B7 family molecules expression.Methods: All stages of CRC were collected, including polyps, adenomas, high-grade neoplasms, and colorectal carcinomas. There were 98 cases of resected CRC tissue, 30 cases of polyps, 30 cases of adenomas, and 25 cases of high-grade neoplasia. Then analysis the expression of three negative costimulatory molecules in all stages of colorectal tissue expression patterns, flow cytometry CD3 + T lymphocytes B7 family molecules to explore the potential value of their expression.Results: The expression of B7 family molecules in 30 cases of polyps, 30 cases of adenomas, 25 cases of highgrade neoplasia, and 98 cases of CRC tissues revealed that the B7-H1 and B7-H3 expression quantity was found in polyps, adenomas, high-grade neoplasms, as well as they were highly expressed in cancerous tissues. B7-H4 was only expressed in cancerous tissues. In the TNM stage of tumor progression, three negative costimulatory molecules were mainly expressed in the cytoplasm of tumor cells. In CRC in lymphocytes B7-H4 expression was related to patient age, mucinous adenocarcinoma, and lymph node metastasis. Survival analysis showed in CRC it was statistically significant that that the expression of B7-H3 and the survival rate of patients. We found that 92.9% of CRC patients expressed B7 family negative costimulatory molecules in varying degrees, and the prognosis and co-expression of B7 family negative co-stimulatory molecules were negatively correlated.Conclusions: Costimulatory molecules B7-H1, B7-H3 were expressed on the early stage of CRC development. The amount of CD3 + T lymphocyte infiltration in CRC was positively correlated with the survival of patients. They are the earliest molecules to participate in the progress of CRC developing in B7 family negative molecules. This suggests that B7-H1 and B7-H3 are involved in rectal carcinoma at the junction, as well as it is essential throughout the entire evolutionary process. However, it is in CRC tissues that B7-H4 only get expressed, and different expression patterns may have different clinical significances.

Comparative Analysis and in vitro Experiments of Signatures and Prognostic Value of Immune Checkpoint Genes in Colorectal Cancer

“…This protein acts as a negative regulatory factor in the T cell-mediated immune response in the TME, 33 which has been detected in a variety of cancers and is associated with poor clinical prognosis. 34 In CRC, high expression of B7-H4 in the tumour stroma had higher survival rate than low B7-H4 patients, 35 but because there was no significant correlation observed in cancer foci and the sample size was small, this study did not receive much attention. In the present study, we combined mRNAs expression of ICGs and clinical data from two databases to show that B7-H4 can predict survival in CRC.…”

B7-H3 at the crossroads between tumor plasticity and colorectal cancer progression: a potential target for therapeutic intervention

“…Investigation into the expression of B7 family of proteins in colorectal tissue has revealed that B7-H3 is lowly expressed in normal colon tissue compared to CRC tissue. This feature makes B7-H3 a potential candidate biomarker for the early diagnosis of CRC [ 16 ]. Recent studies on CRC tissue samples showed a negative correlation between the tumor-infiltrating T-lymphocyte level and B7-H3 expression [ 17 ].…”

“…Studies comparing B7-H3 in the lesions of CRC at various stages, such as polyps (benign), adenomas (pre-cancerous), high-grade neoplasms (adenomas with higher risk of progressing into cancer), and cancerous tissues, reported high levels of B7H1 and B7-H3 in the early stage of CRC development. They continued to express in various stages of CRC, such as adenomas, high-grade neoplasms, and cancer [ 16 ]. However, the expression of B7-H4 was reported only in the advanced stage i.e., the CRC.…”

“…Interestingly, immunohistochemistry studies revealed differences in their subcellular localization of B7-H1 and B7-H3 depending on the stage of CRC development [ 16 ]. Peng Lu and co-workers conducted a bioinformatics study on the genes in CRC cells and normal colon cells that function together with B7-H3, and they found that the gene expression was altered according to the activity of B7-H3.…”

“…Closer analysis showed the presence of CD68 + macrophages in both tumor nest and stroma, and it positively correlated with B7-H3 expression on cancer cells. Concerning T-lymphocyte infiltration, flow cytometry analysis for the expression of B7-H3 on CD3 + T-lymphocytes showed significant differences with the adjacent normal tissue [ 16 ]. As the receptor for B7-H3 is not characterized yet, explaining the mechanism of its immunoregulatory role is challenging.…”