ADAMTSL4, a Secreted Glycoprotein, Is a Novel Immune-Related Biomarker for Primary Glioblastoma Multiforme

Abstract

Background Researches on immunotherapy of glioblastoma multiforme (GBM, WHO grade IV) have increased exponentially in recent years. As a targeted therapy, a series of biomarkers have been identified in local tumor tissue, while circulating marker which could be detected in the body fluids is still lacking. ADAMTSL4, a secreted glycoprotein, was earlier found to play a critical role in a prognostic signature for primary GBM (pGBM). We aimed to investigate the role of ADAMTSL4 at transcriptome level and its relationship with clinical practice in pGBM. Methods A cohort of 88 pGBM patients with RNA-seq data from the Chinese Glioma Genome Atlas (CGGA) was analyzed, and 168 pGBM patients from TCGA were included as validation. Several bioinformatic methods and predictive tools were applied to investigate the ADAMTSL4-associated immune microenvironment status. Results We found that ADAMTSL4 was enriched in GBM (WHO grade IV), especially for those with IDH1/2 wild-type and MGMT unmethylated groups. According to the TCGA classification scheme, ADAMTSL4 can act as a potential marker for subtypes with poorer prognosis. Bioinformatic analyses revealed that ADAMTSL4 was significantly correlated to the immune-related processes in GBM (WHO grade IV), especially representing the infiltration of immune cells and complicated tumor microenvironment. Clinically, high expression of ADAMTSL4 was an independent indicator for poor prognosis. Conclusion The expression of ADAMTSL4 is closely related to the clinicopathologic characteristics of pGBM. Meanwhile, it may play a critical role in immune-related processes. As a secreted glycoprotein, ADAMTSL4 is a promising circulating biomarker for pGBM, deserving further investigations.

Chinese Glioma Genome Atlas (CGGA): A Comprehensive Resource with Functional Genomic Data for Chinese Glioma Patients

“…All primary glioma patients with low ADAMTSL4 expression showed better overall survival than did those with high ADAMTSL4 expression (p < 0.0001, Figure 1D, right). The above results from the ‘mRNA data’ section are consistent with our previous study [25]. Similar to the ‘mRNA data’ page, users can also display the methylation/microRNA distribution and perform correlation and survival analyses on the ‘methylation data’ page and the ‘microRNA data’ page, respectively.…”

“…The results show the gene expression pattern in each glioma subtype classified by clinical information. Similar to our previous studies [25], the ADAMTSL4 gene was shown to be differentially expressed according to the WHO 2016 classification based on the IDH mutation and/or 1p/19q co-deletion status (Figure 1D, left). Moreover, a critical feature of the CGGA dataset is the inclusion of recurrent gliomas.…”

CFHR3 is a potential novel biomarker for hepatocellular carcinoma

“…Previous studies demonstrated that tumor immune infiltrates were mostly characterized by tissue-based approaches, such as clear cell renal cell carcinoma 30 and primary glioblastoma multiforme. 31 Immune infiltrates related pathways may contribute to antitumor effects in HCC. 32 In our research, ESTIMATE analysis had shown that high-risk cohorts have higher ESTIMATE, immune, and stromal scores than that in low-risk cohorts.…”

“…Previous studies demonstrated that tumor immune infiltrates were mostly characterized by tissue‐based approaches, such as clear cell renal cell carcinoma and primary glioblastoma multiforme . Immune infiltrates related pathways may contribute to antitumor effects in HCC .…”

Bioinformatics analysis of prognostic value genes in colorectal cancer microenvironment

“…In addition, it played a potential role as a tumor suppressor in thyroid cancer [34]. ADAMTSL4 was immune-related biomarker for primary glioblastoma multiforme [35]. ANKRD1 was a potential molecular target to enhance sensitivity of ovarian cancer to chemotherapy [36].…”