PRMT5-PAK1 Signaling Participates in Metastasis and Is Associated With Poor Prognosis in Human Esophageal Carcinoma.

BACKGROUND/AIM: Protein arginine methyltransferase 5 (PRMT5), a member of the arginine methyltransferases, is an enzyme catalyzing the methylation of arginine residuals of histones and non-histone proteins to serve as one of many critical posttranslational modifications (PTMs). Phosphorylated P21-activated kinase 1 (p-PAK1), a serine/threonine protein kinase family member, is a cytoskeletal protein that plays a critical role in metastasis. We examined the expression of PRMT5 and PAK1 in esophageal squamous cell carcinoma (ESCC) and evaluated the correlation between PRMT5/p-PAK1 and both clinicopathological parameters and prognosis of ESCC patients. MATERIALS AND METHODS: 106 tumor tissues collected from ESCC patients were assessed for PRMT5 and PAK1 expression using immunohistochemistry. Pearson's correlation and Kaplan-Meier analysis were used to estimate the correlation with the clinicopathological parameters and effect on patient survival. Western blot analysis was used to determine the PRMT5/p-PAK1 protein expression. The wound healing assay was performed to assess the effect of PRMT5 on the migration of ESCC cells. RESULTS: PRMT5 is upregulated in ESCC and the level of PRMT5 is correlated with metastasis and can serve as an independent prognostic factor for overall survival (OS). PRMT5 knockdown remarkably inhibited ESCC cell migration with concomitantly reduced levels of phosphorylated PAK1 (p-PAK1) but not total PAK1. Kaplan-Meier analysis showed that the OS of the subgroup of patients with PRMT5high/p-PAK1high is remarkably shorter than those of other subgroups (i.e., PRMT5high/p-PAK1low, PRMT5low/p-PAK1low and PRMT5low/p-PAK1high). CONCLUSION: PRMT5-PAK1 signaling participates in ESCC metastasis and can predict patients' outcomes.

PTPN1 is a prognostic biomarker related to cancer immunity and drug sensitivity: from pan-cancer analysis to validation in breast cancer.

Background: Protein tyrosine phosphatase non-receptor type 1 (PTPN1), a member of the protein tyrosine phosphatase superfamily, has been identified as an oncogene and therapeutic target in various cancers. However, its precise role in determining the prognosis of human cancer and immunological responses remains elusive. This study investigated the relationship between PTPN1 expression and clinical outcomes, immune infiltration, and drug sensitivity in human cancers, which will improve understanding regarding its prognostic value and immunological role in pan-cancer. Methods: The PTPN1 expression profile was obtained from The Cancer Genome Atlas and Cancer Cell Line Encyclopedia databases. Kaplan-Meier, univariate Cox regression, and time-dependent receiver operating characteristic curve analyses were utilized to clarify the relationship between PTPN1 expression and the prognosis of pan-cancer patients. The relationships between PTPN1 expression and the presence of tumor-infiltrated immune cells were analyzed using Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data and Tumor Immune Estimation Resource. The cell counting kit-8 (CCK-8) assay was performed to examine the effects of PTPN1 level on the sensitivity of breast cancer cells to paclitaxel. Immunohistochemistry and immunoblotting were used to investigate the relationship between PTPN1 expression, immune cell infiltration, and immune checkpoint gene expression in human breast cancer tissues and a mouse xenograft model. Results: The pan-cancer analysis revealed that PTPN1 was frequently up-regulated in various cancers. High PTPN1 expression was associated with poor prognosis in most cancers. Furthermore, PTPN1 expression correlated highly with the presence of tumor-infiltrating immune cells and the expression of immune checkpoint pathway marker genes in different cancers. Furthermore, PTPN1 significantly predicted the prognosis for patients undergoing immunotherapy. The results of the CCK-8 viability assay revealed that PTPN1 knockdown increased the sensitivity of MDA-MB-231 and MCF-7 cells to paclitaxel. Finally, our results demonstrated that PTPN1 was associated with immune infiltration and immune checkpoint gene expression in breast cancer. Conclusion: PTPN1 was overexpressed in multiple cancer types and correlated with the clinical outcome and tumor immunity, suggesting it could be a valuable potential prognostic and immunological biomarker for pan-cancer.

Study of the Immediately Detection of Mild Traumatic Brain Injury by Feature Engineering on Electroencephalography.

The electroencephalographic (EEG) diagnosis of mild traumatic brain injury (mTBI) is not usually timely, and the detection is often performed several hours or days after the trauma, leading to a decrease in the accuracy of its detection. In this study, EEG signals are recorded immediately after mTBI by connecting a bipolar single lead to injured animals. And three types of EEG features, namely time domain, frequency domain, and nonlinear dynamics, are screened for optimal feature subset in mTBI detection. First, EEG signals of animals are recorded before and after establishing the animal model of mTBI. Second, signal preprocessing, feature extraction, and feature preprocessing are performed to obtain the full-feature dataset, and 1442 feature subsets are obtained by 15 feature reduction algorithms extracted from combinations of 47 features. Ultimately, the support vector machines and K-nearest neighbor algorithms are trained and tested respectively, and their performance is comprehensively compared to determine the optimal feature subset for mTBI detection. In the EEG dataset collected in this study, a total of eight feature subsets extracted from combinations of original 47 features and classification models with 100% accuracy are obtained. This study shows the perspective of immediately detecting mTBI based on a bipolar single-lead EEG.

Injectable thermosensitive hydrogel-based drug delivery system for local cancer therapy.

Injectable thermosensitive hydrogel has been regarded as attractive drug delivery system, which displays a sol-gel phase transition upon injection in response to temperature. Recently, thermosensitive hydrogel has become a matter of importance in cancer therapy, providing high local drug concentration, sustained release characteristics, minimal invasiveness, and low systemic toxicities. Here, we review the extensive application of thermosensitive hydrogel in local cancer therapy, including chemotherapy, photothermal therapy, photodynamic therapy, gene therapy, chemo-photothermal combined therapy, and chemo-/immuno- combined therapy.