Integrative Analyses and Verification of the Expression and Prognostic Significance for RCN1 in Glioblastoma Multiforme

Abstract

Glioblastoma multiform is a lethal primary brain tumor derived from astrocytic, with a poor prognosis in adults. Reticulocalbin-1 (RCN1) is a calcium-binding protein, dysregulation of which contributes to tumorigenesis and progression in various cancers. The present study aimed to identify the impact of RCN1 on the outcomes of patients with Glioblastoma multiforme (GBM). The study applied two public databases to require RNA sequencing data of Glioblastoma multiform samples with clinical data for the construction of a training set and a validation set, respectively. We used bioinformatic analyses to determine that RCN1 could be an independent factor for the overall survival of Glioblastoma multiform patients. In the training set, the study constructed a predictive prognostic model based on the combination of RCN1 with various clinical parameters for overall survival at 0.5-, 1.0-, and 1.5-years, as well as developed a nomogram, which was further validated by validation set. Pathways analyses indicated that RCN1 was involved in KEAS and MYC pathways and apoptosis. In vitro experiments indicated that RCN1 promoted cell invasion of Glioblastoma multiform cells. These results illustrated the prognostic role of RCN1 for overall survival in Glioblastoma multiform patients, indicated the promotion of RCN1 in cell invasion, and suggested the probability of RCN1 as a potential targeted molecule for treatment in Glioblastoma multiform.

Downregulation of RCN1 promotes pyroptosis in acute myeloid leukemia cells

“…RCN1 has been demonstrated to be highly expressed in a variety of tumor cells and is correlated with patient prognosis in renal cell carcinoma, prostate cancer, glioblastoma, non-small cell lung cancer, oral squamous cell carcinoma, nasopharyngeal cancer, colon cancer, laryngeal cancer, highly aggressive breast cancer, sorafenib-resistant hepatocellular carcinoma cells, and gemcitabine-insensitive human pancreatic adenocarcinoma cells, among others [20][21][22]24,25,27,[55][56][57][58][59][60][61][62][63]. Yoshida et al [64] reported that RCN1 was expressed in lymphatic endothelial cells (T-LECs) and lung cancer cells in lung tumors, but not in lymphatic endothelial cells (N-LECs) in nontumor tissues.…”

“…Reticulocalbin-1 (RCN1), an endoplasmic reticulum protein, plays a crucial role in calcium homeostasis and inhibits ER stress-induced apoptosis [19,20]. In multiple cancers, such as glioblastoma, non-small cell lung cancer, renal cell carcinoma, hepatocellular carcinoma, and oral squamous cell carcinoma, the overexpression of RCN1 has been observed indicating its involvement in tumorigenesis and invasion [21][22][23][24][25]. High levels of RCN1 expression have been associated with sorafenib resistance in hepatocellular carcinoma and doxorubicin resistance in uterine cancer cells [23,26].…”

Identification and characterization of circular RNAs as novel putative biomarkers to predict anti-PD-1 monotherapy response in metastatic melanoma patients – Knowledge from two independent international studies

“…Moreover, we also analyzed the PFS. Finally, the concordance index (C-index) was calculated by cindex function in pec package (v. 2021.10.11), as described previously [33] .…”

Downregulation of RCN1 inhibits esophageal squamous cell carcinoma progression and M2 macrophage polarization

“…There have been reports of RCN1 protein dysregulation in a variety of diseases, including cardiovascular disease [6], neuromuscular disease [7], and [8]tumors. In recent years, RCN1 has received widespread attention due to its important role in tumorigenesis and progression [9][10][11][12][13]. For example, in prostate cancer cells, downregulation of RCN1 promoted apoptosis and necrosis of the cells [13]; in non-small cell lung cancer, high expression of the RCN1 protein was found to be signi cantly associated with poor prognosis in non-small cell lung cancer patients, and inhibition of RCN1 was shown to reduce proliferation, migration, and invasion of lung adenocarcinoma cells [12].…”