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. 2024 Sep 10:14:1445526.
doi: 10.3389/fonc.2024.1445526. eCollection 2024.

CD276 as a promising diagnostic and prognostic biomarker for bladder cancer through bioinformatics and clinical research

Qi Zhou #  1 , Jianhao Xu #  2 , Xuelei Chen  1 , Jun Ouyang  3 , Caiping Mao  1 , Zhiyu Zhang  3
Affiliations

CD276 as a promising diagnostic and prognostic biomarker for bladder cancer through bioinformatics and clinical research

Qi Zhou et al. Front Oncol. .

Abstract

Objective: To assess CD276 expression and explore its relationship with the clinicopathological characteristics and prognosis of patients with bladder cancer.

Methods: In total, RNA-sequencing data and clinical profiles of 436 bladder cancer cases from The Cancer Genome Atlas (TCGA) were assessed using the University of California Santa Cruz Xena (UCSC) platform. We compared the CD276 levels in cancerous and adjacent normal tissues and used the R software for statistical association with the clinical stage, grade, and survival (the overall survival, disease-specific survival, and progression-free survival). A single-gene GSEA analysis on TCGA-BLCA data was performed to explore potential pathways through which CD276 might influence bladder cancer. Additionally, CD276 expression was analyzed by comparing data from 9 cancerous tissues and 3 adjacent normal tissues in the GEO dataset GSE7476. Furthermore, we analyzed 133 cancerous bladder and adjacent tissue samples from the Soochow University Hospital, collected between January 1, 2016, and September 30, 2022, to assess the CD276 protein expression using immunohistochemistry. We examined the relationship between tumor CD276 levels and clinical outcomes and prognosis of bladder cancer.

Results: Bioinformatic analysis revealed elevated CD276 expression in tumors compared to that in adjacent tissues (p<0.05), correlating with poor survival. GSEA revealed that CD276 was significantly involved in extracellular matrix-related pathways. Immunohistochemistry confirmed CD276 overexpression in tumor tissues, with higher levels linked to advanced pathological grades and worse prognosis.

Conclusion: CD276 is markedly upregulated in bladder cancer and associated with severe pathological features, advanced disease, potential for metastasis, and diminished survival rates. It may promote bladder cancer development and progression by influencing extracellular matrix-related-related pathways, making it a viable diagnostic and prognostic biomarker for bladder cancer.

Keywords: CD276 expression; bioinformatics database; bladder cancer; immunohistochemistry; prognosis.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Expression of CD276 in bladder cancer tissues and para-cancer tissues in the TCGA database and the difference between the two groups. A significant difference was noted in the expression level of CD276 between 408 tumor tissues and 19 para-cancer tissues (p<0.001). CD276, cluster of differentiation 276; TCGA, The Cancer Genome Atlas, TPM, Transcripts Per Million; ***, p<0.001.
Figure 2
Figure 2
Expression and relationship of CD276 with different clinical characteristics in bladder cancer in TCGA database. (A)CD276 Expression levels in bladder tumor patients of different genders. (B) Expression level of CD276 in bladder tumors of different age groups (p<0.05). (C) Expression level of CD276 in bladder tumor tissues with different pathological grades (p<0.001). (D) Expression level of CD276 in bladder tumor tissues of different staging groups (p<0.01). CD276, cluster of differentiation 276; TCGA, The Cancer Genome Atlas; BLCA, bladder cancer, TPM, Transcripts Per Million.
Figure 3
Figure 3
Relationship between the expression of CD276 in bladder cancer and survival of patients in TCGA database. (A) Association between the expression of CD276 and OS in bladder cancer patients(p=0.006). (B) Association between CD276 expression and DSS in bladder cancer patients (p=0.008). (C) Association between the expression of CD276 and PFS in bladder cancer patients(p=0.038). CD276, cluster of differentiation 276; TCGA, The Cancer Genome Atlas; OS, overall survival; DSS, disease-specific survival; PFS, progression-free survival; BLCA, bladder cancer.
Figure 4
Figure 4
Expression of CD276 in bladder cancer tissues and para-cancer tissues in the GEO database and the difference between the two groups. The expression level of CD276 in 9 bladder tumor tissues was higher than that in 3 para-cancer tissues. CD276, cluster of differentiation 276; GEO, Gene Expression Omnibus, TPM, Transcripts Per Million; *, p<0.05.
Figure 5
Figure 5
The high CD276 expression group in patients with bladder cancer based on GSEA. (A) The top 10 pathways enriched in the high CD276 expression data set; (B–E) The high CD276 expression data set was enriched in core matrisome, matrisome, extracellular matrix organization, and ECM glycoproteins pathways. CD276, cluster of differentiation 276; GESA, gene set enrichment analysis.
Figure 6
Figure 6
Expression of CD276 in bladder cancer and para-cancer tissues. (A) Negative expression of CD276 in bladder cancer (100x). (B) Negative expression of CD276 in bladder cancer (200x). (C) Positive expression of CD276 in bladder cancer (100x). (D) Positive expression of CD276 in bladder cancer (200x). (E) Negative expression of CD276 in para-cancer tissues (100x). (F) Negative expression of CD276 in para-cancer tissues (200x). (G) Positive expression of CD276 in para-cancer tissues (100x). (H) Positive expression of CD276 in para-cancer tissues (200x). CD276, cluster of differentiation 276.
Figure 7
Figure 7
Survival curve of PFS and OS for patients with high or low CD276 expression in bladder cancer. (A) Survival curve of PFS for patients with high or low CD276 expression in bladder cancer. (B) Survival curve of OS for patients with high or low CD276 expression in bladder cancer. CD276, cluster of differentiation 276; PFS, progress-free survival; OS, overall survival; HR, hazard ratio.
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