Overexpression of PRKCH promotes tumorigenesis in patients with glioma and influences glioma stem cell properties

Glioma is the most common primary tumor of the central nervous system, with a high recurrence rate, poor prognosis, and low survival rate [1]. The prognosis of different grades of gliomas varies greatly. According to the 2021 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) [2], [3], Low Grade Glioma (LGG) is a diverse group of primary brain tumors, including oligodendrogliomas and astrocytoma, traditionally defined as histological grades 2,3, the annual incidence of LGG is approximately 0.7 per 100,000 people, and this number is still rising [4]. Glioblastoma (GBM) is a highly malignant tumor, CNS WHO grade 4, characterized by rapid progression and poor prognosis, with a median survival of only 16–18 months for newly diagnosed GBM [4]. The current diagnosis of glioma includes preoperative imaging diagnosis, intraoperative and postoperative pathological diagnosis. Clinical treatment is mainly surgery, adjuvant radiotherapy and chemotherapy. Since the 2016 WHO Classification of Tumors of the CNS [5], IDH, 1p/19q, GAMT and other molecules have been included in the classification standards, and so on, but they have not been widely used in the diagnosis of glioma and treatment.

The protein kinase C (PKC) family promotes cell signal transduction and regulates the cell cycle. PRKCH (PKC-eta, PKCη) belongs to the PKC family, which regulates cell proliferation, differentiation and death [6], [7], [8]. PRKCH has been shown to regulate cancer cell proliferation and increase chemoresistance in a variety of cancers, including glioblastoma [9], breast cancer [10], non-small cell lung cancer [11], and acute myeloid leukemia [6]. Our study shows that PRKCH expression is closely related to glioma grade and can predict the prognosis of glioma patients by analyzing the data of CGGA database and TCGA database and 160 cases collected in Hospital of Northern Theater Command.

Glioblastoma stem cells (GSCs) have stem cell characteristics but are not necessarily derived from normal stem cells, they are capable of self-renewal, proliferation and differentiation into various types of cells, such as neurons, astrocytes and oligodendrocytes Plasma cells, which underlie the heterogeneity of GSCs [12]. Because GSCs are pluripotent and maintain low mitotic activity and abundance within tumors, they can survive drugs targeting rapidly proliferating cells, thus contributing to disease recurrence and drug resistance [13]. Complete eradication of GSCs is difficult with currently available treatments. It has become a new strategy for the treatment of glioma to promot GSCs to differentiate [14]. After GSCs differentiating, their stemness and pluripotency are reduced. Our study shows that overexpression of PRKCH promotes tumorigenesis in glioma patients and affects glioma stem cell properties.

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