Increased Expression of LAMTOR5 Predicts Poor Prognosis and Is Associated with Lymph Node Metastasis of Head and Neck Squamous Cell Carcinoma

Abstract

Late endosomal/lysosomal adaptor and MAPK and mTOR activator 5 (LAMTOR5) is a novel oncoprotein associated with several human malignancies, but its clinical role in head and neck squamous cell carcinoma (HNSCC) remains unclear. The present study aims to investigate the clinical and pathological significance of LAMTOR5 in HNSCC. We utilized immunohistochemical staining of human tissue microarrays (210 primary HNSCC, 42 normal oral mucosae, 69 oral epithelial dysplasia, and 68 metastasis lymph nodes) to explore the clinical and pathological significance of LAMTOR5 in HNSCC. Additionally, expression level of LAMTOR5 in immunoreactivity of Pten conditional knock out ( Pten cKO) mice HNSCC was also assessed. We found LAMTOR5 was overexpressed in human and Pten cKO mice HNSCC, and its expression was significantly associated with patients' overall survival, lymph node metastasis and lymph node grade. Furthermore, LAMTOR5 expression was significantly correlated with the expression of p-Akt Ser473 , p-S6 Ser235/236 , immune checkpoints (PD-L1, Galectin 9, VISTA and B7-H4) and macrophage markers (CD68 and CD163). In Pten cKO mice HNSCC, it was also significantly correlated with VISTA and F4/80. Consequently, we consider that high expression of LAMTOR5 might be a poor prognostic indicator and correlated with the immunosuppression of tumor microenvironment.

Terlipressin relieves intestinal and renal injuries induced by acute mesenteric ischemia via PI3K/Akt pathway

“…Interestingly, by activating PI3K/Akt signaling, vasopressin also exerts its ability to inhibit the activation of downstream NF-κB and the upregulation of inflammatory mediators in macrophage induced by endotoxin [32]. It has been widely proven that the activation of PI3K/Akt signaling could reduce the M1 polarization by downregulating the TLR signaling and activating mTOR which then decreases the NF-κB activation [36,37]. Previous studies have shown that Akt isoforms hold the key role in the regulation of macrophage activation [36,38].…”

Increased Expression of SHMT2 Is Associated With Poor Prognosis and Advanced Pathological Grade in Oral Squamous Cell Carcinoma

“…An immunochemistry experiment was performed as previously described ( 25 ). After deparaffinization and dehydration by graded ethanol, the tissues on the microarrays were subjected to antigen retrieval with citric acid buffer (pH = 6.0) in a microwave.…”

“…To analyze the sample staining results, we utilized an Aperio ScanScope CS2 scanner (Vista, CA, United States) to scan the samples of microarrays and to quantify the histoscore at the area we chose from each microarray tissue using Aperio quantification software (Version 9.1) ( 26 , 27 ). The detailed method for the analysis was as reported previously ( 25 ). Using Cluster 3.0, we performed hierarchical clustering analysis among SHMT2 and other correlative proteins ( 25 ).…”

“…The detailed method for the analysis was as reported previously ( 25 ). Using Cluster 3.0, we performed hierarchical clustering analysis among SHMT2 and other correlative proteins ( 25 ). Java TreeView was applied to visualize the correlations described above ( 28 ).…”

“…The best cutoff value is defined as the most significant cutoff value to separate two parts from a group based on the overall survival rate. Kaplan–Meier survival and multivariate analyses were conducted as described ( 25 ). For the correlation analysis of protein expression, we conducted a two-tailed Pearson statistical analysis.…”