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ORIGINAL RESEARCH

BICDL1 Predicts Poor Prognosis and is Correlated with Methylation and Immune Infiltration in Colorectal Cancer

ORCID Icon, , , &
Pages 1109-1126 | Received 25 Aug 2023, Accepted 11 Dec 2023, Published online: 21 Dec 2023
 

Abstract

Background

Bicaudal-D (BICD) Family Like Cargo Adaptor 1 (BICDL1) is an essential component of the molecular mechanism during neuronal development. However, BICDL1 has not been reported in cancer. Using bioinformatics analysis, we systematically evaluated the potential role of BICDL1 in CRC.

Methods

Colorectal cancer (CRC) and normal tissue samples were retrieved from the Gene Expression Omnibus (GEO), Genotype-Tissue Expression (GTEx), and Cancer Genome Atlas (TCGA) databases. Kaplan–Meier (K-M) analysis, nomogram, COX analysis, and receiver operating characteristic (ROC) curves were used to evaluate the prognostic power. Correlation analysis was also conducted to explore the correlation between mRNA expression and the methylation level of BICDL1 using cBioPortal, and the correlation between immune infiltration and BICDL1. RT-qPCR and Western blot assays were performed to analyze BICDL1 expression level between human colorectal cancer cell lines and normal colonic epithelial cells.

Results

BICDL1 had a higher expression in CRC tissues than in normal tissues (p < 0.001) in TCGA and GES 74602 datasets. Kaplan-Meier survival analysis revealed that patients with high BICDL1 expression had lower overall survival (OS) (1.53, 95% confidence interval: 1.07–2.17, p=0.019). The ROC curves demonstrated that BICDL1 has high specificity and efficiency in diagnosis (AUC=0.919, CI: 0.895–0.943). The expression level of BICDL1 was significantly correlated with the infiltrating levels of Treg (R=0.146, p <0.001), TFH (R=0.080, p=0.043), NK CD56bright cells (R=0.149, p <0.001), aDC (R=0.095, p=0.016), and T helper cell infiltration (R=−0.084, p=0.034). The correlation between BICDL1 expression and methylation levels was negative (R2=0.134, p <0.001), and CRC patients had lower methylation levels than normal people (p=0.036). BICDL1 mRNA and its protein expression levels in CRC cell lines (SW620) was markedly increased compared with that of normal colonic epithelial cells (NCM460) (p < 0.001).

Conclusion

BICDL1 may be a potential biomarker for evaluating immune infiltration levels and prognosis of CRC.

Data Sharing Statement

The datasets [GENERATED/ANALYZED] for this study could be found in The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO).

Ethical Approval

This study is based on open-source data, there are no ethical issues and other conflicts of interest. Thus, the study was exempted from the approval of local ethics committees (Ethics Committees of Chenzhou NO. 1 People’s Hospital).

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Funding

The study was supported by National Nature Science Foundation of China (China, grand no: 82004312; 81774287; 81774163;82374462), Hunan Nature Science Foundation (Hunan, China, grand no: 2021JJ30421; 2021JJ40312; 2023JJ50376), Hunan Provincial Health Commission (Hunan, China, grand no: B202304018407), Hunan Innovative Scientific Programme (Hunan, China, grand no: 2021SK51006; Changsha Nature Science Foundation (Changsha, Hunan, China, grand no: Kq2014204), Science Foundation of Ministry of Education of Hunan (Hunan, China, grand no: 20B443), Science Foundation of Health Commission of Hunan (Hunan, China, grand no: 20201066; 20201248), Science Foundation of Hunan Administration of Traditional Chinese Medicine (Hunan, China, grand no: 2021248; D2022125) and Science Foundation of Hunan Academy of Chinese Medicine (Hunan, China, grand no: 201604). Technology research and development center project of chenzhou (Hunan, China, grand no: 2021-40). Research project of Chenzhou NO.1 People’s Hospital (chenzhou, Hunan, China, grand no: CZYY202206; JG2022-012; 2020A27; 2020XJ118).