Dataset Information

ITGB4 as a novel serum diagnosis biomarker and potential therapeutic target for colorectal cancer.

ABSTRACT:

Purpose

To develop new and effective biomarkers for the diagnosis of colorectal cancer (CRC).

Experimental design

The serum expression of ITGB4 (49 CRC and 367 HC) was detected by enzyme-linked immunosorbent assay (ELISA), and its diagnostic value was analyzed using the receiver operating characteristic (ROC) curve. The sensitivity and specificity of ITGB4 in CRC diagnosis were calculated through statistical analysis. The optimal clinical cutoff value was calculated using the Youden index, and diagnostic efficacy was analyzed in a larger serum sample (98 CRC and 1631 non-CRC). The expression of ITGB4 was measured by CyTOF (cell experimental technology) at the single-cell level, and characteristics were analyzed using viSNE and SPADE TREE.

Results

Serum ITGB4 and CEA levels were significantly higher in CRC patients than in HC and non-CRC patients. The use of serum ITGB4 levels for the diagnosis of CRC has a high sensitivity (79%) but not high specificity when the clinical cutoff value was 0.70 ng/mL. However, the optimal cutoff value was 1.6 ng/mL with 86.2% specificity and 52.0% sensitivity, and the diagnostic efficacy was greatly improved with high specificity (82.0%) and sensitivity (71.4%) when combined with CEA. ITGB4 expression characteristics were measured and related to the expression of EpCAM, Ck8/18, and perforin at the single-cell level. Single-cell analysis showed that cell clusters with low expression of CK8/18 and ITGB4 were more sensitive to 5FU and radiotherapy (RT).

Conclusions

ITGB4 is an effective diagnostic serum biomarker and a potential therapeutic target for CRC.

SUBMITTER: Jiang X

PROVIDER: S-EPMC8495272 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe incidence of colorectal cancer in humans is high, and it is in the top five for cancer-related morbidity and mortality. It is one of the main threats to human health. The function of long noncoding RNAs in tumor occurrence and development has gradually gained attention in recent years. In increasing numbers of studies, researchers have demonstrated that it plays an important role in the pathogenesis of colorectal cancer.AimTo find out if long noncoding RNA RP5-881L22.5 played a role in the pathogenesis of colorectal cancer in relation to the tumor microenvironment.MethodsWe analyzed the transcriptome data and clinical data in The Cancer Genome Atlas-colon adenocarcinoma. The CIRBERSORT algorithm was applied to evaluate these tumor-infiltrating immune cells in The Cancer Genome Atlas-colon adenocarcinoma cancer tissue samples. Using the "estimate" package in R, we assessed the tumor immune microenvironment. The expression level of RP5-881L22.5 in tumor tissue and adjacent normal tissue samples from 4 pairs of colorectal cancer patients was determined by quantitative reverse transcription PCR. Colorectal cancer cells were tested for invasiveness using a transwell invasion assay after RP5-881L22.5 expression was knocked down.ResultsThe expression of lncRNA RP5-881L22.5 was related to the clinical characteristics of the tumors, and it was negatively related to the infiltration level of immune cells in the tumor microenvironment and the expression of T cell inhibitory receptors. A major function of its coexpressed mRNA was to regulate tumor immunity, such as the immune response. When quantitative reverse transcription PCR was performed on tumor tissues from 4 pairs of colorectal cancer patients, the results showed that RP5-881L22.5 was highly expressed. Subsequently, knocking down the expression of RP5-881L22.5, the invasiveness of colorectal cancer cell lines was reduced, and the apoptosis rate was increased.ConclusionRP5-881L22.5 plays a crucial role in the microenvironment of tumors as well as in the pathogenesis of colorectal cancer. The relationship between RP5-881L22.5 and the tumor immune microenvironment deserves further study.