Myelin and lymphocyte protein serves as a prognostic biomarker and is closely associated with the tumor microenvironment in the nephroblastoma

Abstract

Nephroblastoma, also known as Wilms' tumor (WT), is the most common renal tumor that occurs in children. Although the efficacy of treatment has been significantly improved by a series of comprehensive treatments, some patients still have poor prognosis. Myelin and lymphocyte (MAL) protein, a highly hydrophobic integrated membrane‐bound protein, has been implicated in many tumors and is also closely linked to kidney development. However, the relationship between MAL and WT has not yet been elucidated. Therefore, we attempted to evaluate the feasibility of MAL as a promising prognosis factor for WT. The differential expression of MAL was investigated using TARGET database and was verified using the Gene Expression Omnibus database and real‐time quantitative PCR. The prognostic ability of MAL was determined using Kaplan–Meier and Cox regression analyses. Pearson correlation analysis was applied to explore the relationship between MAL expression and methylation sites. The ESTIMATE and CIBERSORT algorithms showed that MAL expression was associated with the WT tumor microenvironment. Gene Set Enrichment Analysis (GSEA) indicated that multiple signaling pathways closely associated with tumorigenesis were differentially enriched between the high‐ and low‐MAL groups. In conclusion, our study comprehensively explored the potential of MAL as a prognosis factor for WT. Meanwhile, we also demonstrated that MAL, as a prognostic factor for WT, may be closely related to the tumor microenvironment.

FOXO3a‑modulated DEPDC1 promotes malignant progression of nephroblastoma via the Wnt/β‑catenin signaling pathway

“…A recent study revealed that increased expression of DEPDC1 leads to poor survival in patients with nephroblastoma ( 36 ). Su et al ( 5 ) found that DEPDC1 is highly expressed in nephroblastoma and associated with poor survival using database network analysis. The present study investigated the role and underlying mechanism of DEPDC1 in nephroblastoma progression.…”

“…The improvement of treatment methods has led to long-term survival rate of >90% ( 4 ); thus nephroblastoma has one of the best prognoses among types of pediatric cancer. However, certain patients still experience poor prognosis due to cancer recurrence and metastasis ( 5 ). Therefore, discovering targeted biomarkers of nephroblastoma may contribute to understanding of the pathogenesis and metastatic mechanism and development of novel therapeutic strategies for management of patients with nephroblastoma.…”

“…In addition, other studies have shown that DEPDC1 participates in tumorigenesis and cancer progression in lung adenocarcinoma ( 9 ), gastric cancer ( 10 ), oral squamous cell carcinoma ( 11 ) and colorectal ( 12 ), liver ( 13 ) and breast cancer ( 14 ). By analyzing Therapeutically Applicable Research to Generate Effective Treatments database, Su et al ( 5 ) found that DEPDC1 is highly expressed in nephroblastoma and is associated with poor patient survival, indicating that DEPDC1 may serve as a potential prognostic and diagnostic biomarker for nephroblastoma. To the best of our knowledge, however, the role of DEPDC1 in the onset and development of nephroblastoma have not been investigated.…”

The MAL Family of Proteins: Normal Function, Expression in Cancer, and Potential Use as Cancer Biomarkers

“…Reports about promoter methylation of MAL-family genes in cancer are available only for MAL, MAL2, and MALL. Hypermethylation of MAL was found in BRCA [67,122], CESC [87], COAD-READ [77][78][79]81,82,123,124], ESCA [125], HNSC [70,71,74], Wilm's tumor [126], LUSC [83,84], STAD [75], and PRAD [127,128]. Hypermethylation of MAL2 was observed in malignant meningioma [110], and of MALL in COAD-READ [113], but not in CESC [85].…”

Wnt/β-Catenin Signaling Pathway in Pediatric Tumors: Implications for Diagnosis and Treatment

“…DEP domain containing 1 (DEPDC1) is an important modulator of the Wnt pathway, reported as a tumor-related gene that promotes carcinogenesis and is found to be upregulated in numerous cancer types [ 76 ]. DEPDC1 facilitates the malignant transformation of nephroblastoma by employing the Wnt/β-catenin signaling pathway, which may be modulated by forkhead box transcription factor 3a (FOXO3a) [ 77 ]. Su et al revealed that DEPDC1 was overexpressed in nephroblastoma and associated with poor prognosis.…”