Clinicopathologic significance of legumain overexpression in cancer: a systematic review and meta-analysis

Abstract

Since reports on the clinical significance of legumain in cancer have shown inconsistent results, we systematically evaluated clinical indicators of legumain in cancer. We searched the Cochrane Library, PubMed, Embase, and EBSCO databases and the Wangfang and CNKI databases in China by using “legumain” and (“neoplasms” OR “cancer”) as search terms. We included case-controlled studies of legumain and cancer. The quality of the studies was evaluated by using Lichtenstein’s guidelines, and valid data was extracted for analysis. In total, 10 articles were included in this study. Meta-analysis showed that legumain was overexpressed in cancer compared with in normal tissue and was higher in stage III–IV disease than in I–II disease. Moreover, legumain overexpression was correlated with poor prognosis and clinical stage. Furthermore, Cancer Genome Atlas data showed that among patients with rectal cancer, those with tumors overexpressing legumain had shorter overall survival than those in the low expression group (P < 0.05). Legumain appears to be involved in tumor development and deterioration; thus, it can potentially be developed into both a marker for monitoring and diagnosing tumors and a therapeutic target.

Potential Human Health Applications from Marine Biomedical Research with Elasmobranch Fishes

“…A recent comparison of gene transcripts between white shark, C. carcharias, and zebrafish, Danio rerio, revealed the surprising result that white shark gene products associated with metabolism, molecular functions, and the cellular locations of these functions were more similar to human than to zebrafish [38]. In fact, these same shark transcriptome gene expression studies have identified positive selection for genes, such as legumain, that play important roles in immune system responses to certain cancers, including colorectal cancer [44]. An interesting feature of the shark genome is the high proportion of dinucleotide microsatellite repeats, with a lower abundance than other vertebrates of repeating trinucleotide DNA sequences [38].…”

“…An interesting feature of the shark genome is the high proportion of dinucleotide microsatellite repeats, with a lower abundance than other vertebrates of repeating trinucleotide DNA sequences [38]. This observation is worthy of note as abnormally higher numbers of trinucleotide repeats in humans have been linked to a variety of neurological disorders, including spinobulbar muscular atrophy, myotonic dystrophy, and Huntington's disease, as well as certain types of cancer (i.e., hereditary nonpolyposis colon carcinoma and sporadic bladder carcinoma) [44][45][46][47][48][49]. While it is difficult to assess neurological disease in elasmobranchs, the relatively lower proportion of trinucleotide microsatellite repeats in the white shark genome may provide a genetic mechanism for the relatively low incidence of malignant neoplasia among elasmobranchs [38].…”

Two-step polymer- and liposome-enzyme prodrug therapies for cancer: PDEPT and PELT concepts and future perspectives

“…Legumain is an asparaginyl endopeptidase overexpressed in several cancers [127], both in the extracellular matrix (ECM) and in the lysosomes. Therefore, linkers presenting asparagine or aspartic acid residues, selectively hydrolysable by this enzyme, have been used to develop enzyme-sensitive prodrugs.…”

EIF4E regulates STEAP1 expression in peritoneal metastasis

“…In addition, the tumor suppressor RNA binding protein, poly r(C) binding protein 1 (PCBP1), regulates miR-3978 expression in normal peritoneum and is itself downregulated during metastatic progression, in turn switching on events ultimately resulting in overexpression of legumain [9,14]. Since legumain can potentiate metastatic progression by proteolytic activation of other zymogens or by promoting the epithelial to mesenchymal transition (EMT) via Akt and MAPK signaling [15][16][17][18], and suppression of PCBP1 expression or post-translational modification via Akt2-mediated phosphorylation promotes EMT and metastasis via upregulation of specific regulatory proteins and long non-coding RNAs in lung, breast, and gastric cancer [19][20][21][22][23], we enquired the translational landscape of EMT inducers in metastatic gastric cancer and discovered that Ivyspring International Publisher STEAP1 (encoding six-transmembrane epithelial antigen of the prostate 1) is translationally upregulated [24]. Expression of STEAP1 was required for both tumorigenesis per se, as well as for induction of chemoresistance [24].…”