Bioinformatics analysis of prognostic significance of COL10A1 in breast cancer

Abstract

Background: Collagen type X alpha 1 (COL10A1) is overexpressed in diverse tumors and displays vital roles in tumorigenesis. However, the prognostic value of COL10A1 in breast cancer remains unclear.

Methods: The expression of COL10A1 was analyzed by the Oncomine database and UALCAN cancer database. The relationship between COL10A1 expression level and clinical indicators including prognostic data in breast cancer were analyzed by the Kaplan-Meier Plotter, PrognoScan, and Breast Cancer Gene-Expression Miner (bc-GenExMiner) databases.

Results: COL10A1 was up-regulated in different subtypes of breast cancer. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) status and nodal status were positively correlated with COL10A1 expression. Conversely, age, the Scarff-Bloom-Richardson (SBR) grade, basal-like status, and triple-negative status were negatively related to COL10A1 level in breast cancer samples compared with normal tissues. Patients with increased COL10A1 expression level showed worse overall survival (OS), relapse-free survival (RFS), distant metastasis-free survival (DMFS) and disease-free survival (DFS). COL10A1 was positively correlated with metastatic relapse-free survival. GSEA analysis revealed that enrichment of TGF-β signaling pathway. 15-leucine-rich repeat containing membrane protein (LRRC15) is a correlated gene of COL10A1.

Conclusion: Bioinformatics analysis revealed that COL10A1 might be considered as a predictive biomarker for prognosis of breast cancer. Further experiments and clinical trials are essential to elucidate the value of COL10A1 in breast cancer treatment.

Keywords: Bioinformatics analysis; COL10A1; Prognosis; breast cancers.

Figure 1. The mRNA and protein expression of COL10A1 in breast cancer compared to normal

The mRNA expression of COL10A1 in different subtypes of breast cancer compared to normal individuals derived from the Oncomine database. Data shown for male breast carcinoma (A), intraductal cribriform breast adenocarcinoma (B), invasive breast carcinoma (C), invasive lobular breast carcinoma (D), invasive ductal breast carcinoma (E), mixed lobular and ductal breast carcinoma (F), ductal breast carcinoma in situ stroma (G), invasive ductal breast carcinoma stroma (H) and ductal breast carcinoma (I). * stands for the maximum and minimum values. (J) The protein expression of COL10A1 in primary breast cancer and normal tissues analyzed by UALCAN cancer database. Z-values represent standard deviations from the median across samples for the given cancer type. Log2 Spectral count ratio values from CPTAC were first normalized within each sample profile, then normalized across samples.

Figure 2. Box plot revealing the relationship between COL10A1 expression and different clinical indicators using the bc-GenExMiner software

Data shown for age (A), SBR (B), ER (C), PR (D), HER-2 (E), nodal status (F), basal-like status (G) and triple-negative status (H).

Figure 3. Survival data evaluating the prognostic value of COL10A1 and the GSEA analysis

Analysis is shown for OS (A), RFS (B) by Kaplan–Meier Plotter and metastatic RFS (C) by bc-GenExMiner database. (D) The relationship between the protein expression of COL10A1 and prognosis by Kaplan–Meier Plotter (E) GSEA analysis obtained from LinkedOmics Dataset.

Figure 4. Co-expression analysis of COL10A1

(A) Co-expression profile of COL10A1 identified using the Oncomine database. (B,C) Showed the correlation between COL10A1 and LRRC15 expression in breast cancer by the bc-GenExMiner software. (D) Heat map of COL10A1 and LRRC15 expression across PAM50 breast cancer subtypes in the TCGA database obtained from the UCSC Xena web-based tool.

Figure 5. The expression and survival data indicating the potential function of LRRC15 in breast cancer

(A) The expression of LRRC15 showed by GEPIA database. (B) The OS status for the expression of LRRC15 from Kaplan–Meier Plotter.