SLC15A4 Serves as a Novel Prognostic Biomarker and Target for Lung Adenocarcinoma

Abstract

BackgroundSLC15A family members are known as electrogenic transporters that take up peptides into cells through the proton-motive force. Accumulating evidence indicates that aberrant expression of SLC15A family members may play crucial roles in tumorigenesis and tumor progression in various cancers, as they participate in tumor metabolism. However, the exact prognostic role of each member of the SLC15A family in human lung cancer has not yet been elucidated.Materials and MethodsWe investigated the SLC15A family members in lung cancer through accumulated data from TCGA and other available online databases by integrated bioinformatics analysis to reveal the prognostic value, potential clinical application and underlying molecular mechanisms of SLC15A family members in lung cancer.ResultsAlthough all family members exhibited an association with the clinical outcomes of patients with NSCLC, we found that none of them could be used for squamous cell carcinoma of the lung and that SLC15A2 and SLC15A4 could serve as biomarkers for lung adenocarcinoma. In addition, we further investigated SLC15A4-related genes and regulatory networks, revealing its core molecular pathways in lung adenocarcinoma. Moreover, the IHC staining pattern of SLC15A4 in lung adenocarcinoma may help clinicians predict clinical outcomes.ConclusionSLC15A4 could be used as a survival prediction biomarker for lung adenocarcinoma due to its potential role in cell division regulation. However, more studies including large patient cohorts are required to validate the clinical utility of SLC15A4 in lung adenocarcinoma.

Functional Characterization of the Lysosomal Peptide/Histidine Transporter PHT1 (SLC15A4) by Solid Supported Membrane Electrophysiology (SSME)

“…Taken together, these findings demonstrate that PHT1 (SLC15A4) plays a key role in the immune response, so it is not surprising that several studies have implicated PHT1 in the development of diseases associated with immune dysfunction, such as systemic lupus erythematosus (SLE) [18][19][20][21][22] and inflammatory bowel disease (IBD) [19]. In addition, PHT1 has been implicated in other human diseases such as type 2 diabetes [23], combined pituitary hormone deficiency [24] and lung adenocarcinoma [25].…”

SL-scan identifies synthetic lethal interactions in cancer using metabolic networks

“…Previous studies have shown that inheriting the CYP3A4*1B allele may increase susceptibility to early-onset menarche, which is a known risk factor for breast cancer 44 . Furthermore, studies have reported that the expression levels of SLC15A2 RNA were lower in lung cancer tissues than in normal tissues 45 . Another example of a promising SL pair predicted by SL-scan is PLCG1-LDHAL6A in bile duct.…”

HPV‐negative head and neck cancers with adverse pathological features carry specific molecular changes that are associated with survival

“…Tumors with positive PNI also demonstrated low SLC15A4 methylation and high TNFAIP8L1 methylation associated with poor survival. Although the role of the peptide transporter SLC15A4 in cancer is not well‐studied, it has been implicated in the cell cycle and cancer cell proliferation in vitro and be modulated by drugs like nateglinide and glibenclamide 37 . On the other hand, the strong association of TNFAIP8 with cancer development is better‐understood, although its specific effect on survival is context‐dependent 38 .…”

“…Although the role of the peptide transporter SLC15A4 in cancer is not well-studied, it has been implicated in the cell cycle and cancer cell proliferation in vitro and be modulated by drugs like nateglinide and glibenclamide. 37 On the other hand, the strong association of TNFAIP8 with cancer development is better-understood, although its specific effect on survival is context-dependent. 38 TNFAIP8 expression increases in stage II and III liver cancer and decreases in stage IV, and its expression may similarly be suppressed through increased methylation in PNI-positive HNSCC tumors which tend to be stage IV.…”