Identifying the Prognostic Risk Factors of Synaptojanin 2 and Its Underlying Perturbations Pathways in Hepatocellular Carcinoma

Abstract

Synaptojanin 2 (SYNJ2) regulates cell proliferation and apoptosis via dephosphorylating plasma membrane phosphoinositides. Aim of this study is to first seek the full-scale expression levels and potential emerging roles of SYNJ2 in hepatocellular carcinoma (HCC). We systematically analyzed SYNJ2 mRNA expression and protein levels in HCC tissues based on large-scale data and in-house immunohistochemistry (IHC). The clinical significance and risk factors for SYNJ2-related HCC cases were identified. A nomogram of prognosis was created and its performance was validated by concordance index (C-index) and shown in calibration plots. Based on the identified differentially coexpressed genes (DCGs) of SYNJ2, enriched annotations and potential pathways were predicted, and the protein interacting networks were mapped. Upregulated SYNJ2 in 3,728 HCC and 3,203 non-HCC tissues were verified and in-house IHC showed higher protein levels of SYNJ2 in HCC tissues. Pathologic T stage was identified as a risk factor. Upregulated mRNA levels and mutated SYNJ2 might cause a poorer outcome. The C-index of the nomogram model constructed by SYNJ2 level, age, gender, TNM classification, grade, and stage was evaluated as 0.643 (95% CI = 0.619-0.668) with well-calibrated plots. A total of 2,533 DCGs were extracted and mainly functioned together with SYNJ2 in metabolic pathways. Possible transcriptional axis of CTCF/ POLR2A-SYNJ2/INPP5B (transcription factor-target) in metabolic pathways was discovered based on ChIP-seq datasets. In summary, transcriptional regulatory axis CTCF/POLR2A-SYNJ2 might influence SYNJ2 expression levels. Increased SYNJ2 expression level could be utilized for predicting HCC prognosis and potentially accelerates the occurrence and development of HCC via metabolic perturbations pathways.

SYNJ2 is a novel and potential biomarker for the prediction and treatment of cancers: from lung squamous cell carcinoma to pan-cancer

“…Distinct SYNJ2 expression levels were identified in 14 types of cancer cell lines. Previous research showed differential expression levels of SYNJ2 between some cancers (e.g., BRCA [ 14 ] and LIHC [ 32 ]) and their control samples, and our study further comprehensively analyzed 20 cancers and revealed that increased and decreased SYNJ2 expression levels were defined in seven cancers (CHOL, COAD, LIHC, LUAD, LUSC, PRAD, and STAD) and four cancers (GBM, KICH, KIRC, and KIRP), respectively. SYNJ2 expression made it feasible to differentiate multiple types of cancers from their corresponding normal samples with at least moderate accuracy, suggesting its potential in identifying cancer status.…”

“…Previous studies have reported that SYNJ2 is responsible for tumor initiation and progression. With genetic changes, SYNJ2 triggers colorectal cancer [ 10 ], medulloblastoma [ 9 ], prostate cancer [ 11 ], and hepatocellular carcinoma [ 32 ]. Overexpressed SYNJ2 boosts the invasion and migration of glioma [ 13 ] and breast cancer cells and prompts poor prognosis for cancer patients [ 14 ].…”

Decreased INPP5B expression predicts poor prognosis in lung adenocarcinoma

“…These results were consistent with a recent study in which a high mutation rate of INPP5B was observed in the genome-wide mapping of melanocytic neoplasms [ 25 ]. Furthermore, changes in the expression of INPP5B have also been found in the metabolomic data of hepatocellular carcinoma [ 26 ]. These findings suggested that loss of function or lower functioning of INPP5B might be related to the initiation and progression of tumors.…”

POLR2A Promotes the Proliferation of Gastric Cancer Cells by Advancing the Overall Cell Cycle Progression

“…Besides, studies had reported that POLR2A gene polymorphism was associated with lower survival outcomes in patients with non-small cell lung cancer ( Sainsbury et al, 2015 ). In addition, Zhang et al discovered the key potential transcription axis of CTCF/POLR2A—SYNJ2/INPP5B in metabolic programs based on the ChIP-seq data set, speculated that CTCF/POLR2A could directly dysregulate SYNJ2 levels and that increased SYNJ2 would affect HCC development via metabolic perturbation pathways ( Zhang et al, 2021 ). The above studies consistently show that POLR2A promotes tumor growth and is related to poor prognosis.…”