PODXL might be a new prognostic biomarker in various cancers: a meta-analysis and sequential verification with TCGA datasets

Abstract

Background: Several studies have investigated the associations between the podocalyxin-like protein (PODXL) expression quantity or locations and cancers survival, but the results were far from conclusive. Therefore, we proceeded a meta-analysis on PODXL in various human cancers to find its prognostic value and followed confirmation using the TCGA datasets. Methods: We performed a systematic search, and 18 citations, including 5705 patients were pooled in metaanalysis. The results were verified with TCGA datasets. Results: Total eligible studies comprised 5705 patients with 10 types of cancer. And the result indicated that PODXL high-expression or membrane-expression were significantly related to poor overall survival (OS). However, subgroup analysis showed a significant association between high expressed PODXL and poor OS in the colorectal cancer, pancreatic cancer, urothelial bladder cancer, renal cell carcinoma and glioblastoma multiforme. Then, we validated the inference using TCGA datasets, and the consistent results were demonstrated in patients with pancreatic cancer, glioblastoma multiforme, gastric cancer, esophageal cancer and lung adenocarcinoma. Conclusion: The result of meta-analysis showed that high expressed PODXL was significantly linked with poor OS in pancreatic cancer and glioblastoma multiforme, but not in gastric cancer, esophageal cancer or lung adenocarcinoma. And the membrane expression of PODXL might also associate with poor OS. PODXL may act as tumor promotor and may serve as a potential target for antitumor therapy.

TCF3 Regulates the Proliferation and Apoptosis of Human Spermatogonial Stem Cells by Targeting PODXL

“…Podocalyxin-like protein is a member of CD34 family proteins, which carries numerous post-translational epitopes responsible for various kinds of pluripotent surface biomarkers, including TRA-1-60, mAb84, TRA-1-81, GP200, and GCTM2 (Kang et al, 2016). It is also associated with more than 10 human malignancies (Kang et al, 2016;He et al, 2020). These studies suggest that PODXL may be responsible for the impaired proliferative activity of SSC by TCF3 silencing.…”

“…Those data suggest that TCF3 may influence the adhesion of human SSCs via different downstream targets compared to ESCs. It has been shown that PODXL is a pluripotent surface marker and enriched in many cancer cells (He et al, 2020), PODXL positive hematopoietic stem cells can reconstitute myeloid and lymphoid lineages in recipients with lethal radiation (Doyonnas et al, 2005). PODXL promotes cancer development and aggressiveness by activating MAPK and PIK3 pathways.…”

The RUFYs, a Family of Effector Proteins Involved in Intracellular Trafficking and Cytoskeleton Dynamics

“…Tyrosine phosphorylation of RUFY1 by ETK appears to be important for its endosomal localization and could play an important role promoting tumoral transformation by affecting downstream effectors of PI3-kinase. RUFY1 was also shown to interact with podocalyxin-like protein (PODXL), a transmembrane glycoprotein with anti-adhesive properties associated with poor prognosis of several cancers ( Taniuchi et al, 2018 ; He et al, 2020 ; Table 1 ). Gastric cancer progression is significantly increased upon PODXL expression, a phenotype reduced by concomitant RUFY1 silencing.…”

PCAT6 may be a new prognostic biomarker in various cancers: a meta-analysis and bioinformatics analysis

“…Our understanding of the role of lncRNAs in the progression and suppression of multiple tumors has resulted in novel opportunities to improve the diagnosis and treatment of malignancies [ 17 , 18 ]. Meta-analyses revealed that HOXD-AS1[ 4 ], PODXL [ 19 ], and TP73-AS1 [ 20 ] were associated with the clinicopathological characteristics and prognosis of tumors. LncRNA prostate cancer-associated transcript 6 (PCAT6), which was first identified in keratinocytes, indirectly activates the Wnt/β-catenin pathway by interacting with KLHL12 in cervical cancer cells [ 21 ].…”