Abstract
Poly Adenylate Binding Protein Interacting protein 1 (PAIP1) plays a critical role in translation initiation and is associated with the several cancer types. However, its function and clinical significance have not yet been described in oral squamous cell carcinoma (OSCC) and its associated features like lymph node metastasis (LNM). Here, we used the data available from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) to analyze PAIP1 expression in oral cancer. The publicly available data suggests that PAIP1 mRNA and protein levels were increased in OSCC. The high PAIP1 expression was more evident in samples with advanced stage, LNM, and worse pattern of invasion. Moreover, the in vitro experiments revealed that PAIP1 knockdown attenuated colony forming, the aggressiveness of OSCC cell lines, decreasing MMP9 activity and SRC phosphorylation. Importantly, we found a correlation between PAIP1 and pSRC through the analysis of the IHC scores and CPTAC data in patient samples. Our findings suggest that PAIP1 could be an independent prognostic factor in OSCC with LNM and a suitable therapeutic target to improve OSCC patient outcomes.
Highlights
Tumor metastasis is critical for tumor progression, depending on motility and invasion, cancer cell plasticity, the modulation of the microenvironment, and cancer cell colonization[1]
We found that the copy number was significantly associated with the mRNA
Concurrent with our hypothesis, we found that the genetic alterations seen in head and neck cancers were mostly amplifications with mutations and fusions and a strong correlation between Protein Interacting protein 1 (PAIP1) copy numbers and mRNA levels (Fig. S1a–c)
Summary
Tumor metastasis is critical for tumor progression, depending on motility and invasion, cancer cell plasticity, the modulation of the microenvironment, and cancer cell colonization[1]. OSCC is a common cancer type of the mucosal linings of the oral cavity. LNM is one of the deterministic prognostic indicators in OSCC2. Despite the multimodal approach, including surgery or radiotherapy as treatment approaches in patients with OSCC, the low LNM-associated survival rate of less than 50% remains a major concern[3,4]. There is crucial to identify novel LNM-related biomarkers to improve the clinical outcomes in patients with OSCC. The coding gene of PAIP1is located at 5p12 chromosomal location, encoding a protein of 479 amino acids sharing homology with the central domain of human eukaryotic initiation factor 4G (eIF4G), interacting with the eIF4A and eIF3 complexes to facilitate translation initiation[5–9]
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