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. 2021 Feb 2:2021:6949864.
doi: 10.1155/2021/6949864. eCollection 2021.

Upregulation of Versican Associated with Tumor Progression, Metastasis, and Poor Prognosis in Bladder Carcinoma

Qi Zhang  1 , Junxiu Wu  2 , Xinpeng Chen  3 , Ming Zhao  4 , Dahong Zhang  1 , Feng Gao  5
Affiliations

Upregulation of Versican Associated with Tumor Progression, Metastasis, and Poor Prognosis in Bladder Carcinoma

Qi Zhang et al. Biomed Res Int. .

Abstract

Objective: This work analyzes the role of versican (VCAN) on bladder cancer (BLCA). Versican (VCAN) is a chondroitin sulfate proteoglycan which is important for tumorigenesis and the development of cancer. However, the expression of VCAN on human bladder cancer (BLCA) has been rarely reported.

Methods: The clinical significance of VCAN in BLCA has been determined by our bioinformatics tools. Then, we performed immunohistochemical staining (IHC) and analyzed the correlation between VCAN expression and clinicopathological features.

Results: The bioinformatics results reveal that a high VCAN mRNA level was significantly associated with stage, histological subtype, molecular subtype, and metastasis in BLCA. Furthermore, IHC reveals that expression of VCAN was significantly correlated with the number of tumors, invasion depth, lymph node metastasis, distant metastasis, and histological grade. Kaplan-Meier survival analysis reveals that patients with a high expression of VCAN have poor prognosis than those patients with a low expression of VCAN. According to our result from the bioinformatics database, the mechanism of VCAN in BLCA revealed that VCAN was related to FBN1 and genes of the ECM remodeling pathway (MMP1, MMP2).

Conclusion: VCAN expression might be included in the process of carcinogenesis and prognosis. Hence, VCAN could be a reliable biomarker of the clinical prognosis on BLCA.

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Conflict of interest statement

The authors declare that there are no conflicts of interest regarding the publication of this article.

Figures

Figure 1
Figure 1
The VCAN mRNA level was associated with stage, histological subtype, molecular subtype, and node metastasis of BLCA used by the UALCAN database. N0: no regional lymph node metastasis; N1: metastases in 1 to 3 axillary lymph nodes; N2: metastases in 4 to 9 axillary lymph nodes; N3: metastases in 10 or more axillary lymph nodes. ∗P < 0.05.
Figure 2
Figure 2
Immunohistochemical staining for VCAN in cancerous bladder tissue. (A1–A3) Negative staining in urinary bladder carcinoma. (B1–B3) Weak staining in non-muscle-invasive urinary bladder carcinoma. (C1–C3) Strong staining in muscle-invasive urinary bladder carcinoma. Magnification: the original magnification ×40 (A1–C1), ×100 (A2–C2), and ×200 (A3–C3).
Figure 3
Figure 3
Kaplan-Meier survival curves of bladder carcinoma patients with different levels of VCAN expression.
Figure 4
Figure 4
(a) Hypomethylation of VCAN was associated with progression of BLCA. (b) VCAN is involved in the interaction network in cell adhesion for the ECM remodeling pathway, and the mRNA expression level of VCAN in BLCA was positively correlated with FBN1.
Figure 5
Figure 5
(a) The mRNA expression level of VCAN in BLCA was positively correlated with MMP1 and MMP2 performed by the GEPIA database. (b) The mRNA expression level of VCAN in BLCA was positively correlated with MMP1 and MMP2 performed by the OncoLnc database.
Figure 6
Figure 6
Gene-drug interaction based on the Comparative Toxicogenomics Database. The interaction network showed that several drugs or chemicals such as acetaminophen, cisplatin, and curcumin could increase the mRNA level of VCAN. However, doxorubicin and dexamethasone result in decreased expression of VCAN mRNA.
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