Increased Expression of NXPH4 Correlates with Immune Cell Infiltration and Unfavorable Prognosis in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the leading malignant carcinomas. Despite the advancement in the treatment for HCC, such as precise hepatectomy, radiotherapy, transarterial therapies, chemotherapy, targeted treatments, and immunotherapy, the 5-year overall survival rate of HCC is extremely low. Hence, novel biomarkers are urgently needed for advancing the therapy and prognosis of HCC. Neurexophilin 4 (NXPH4) is a neuropeptide-like glycoprotein. The study is designed to investigate the function of NXPH4 in HCC through a comprehensive bioinformatics analysis. NXPH4 expression status and prognostic values were analyzed via multiple datasets, such as TCGA, GEO, and ICGC. The association between NXPH4 and immune cell infiltration was estimated by TIMER, TISIDB, and CIBERSORT. In vitro, we explored the biological function of NXPH4 in JHH7 and SNU182 cells through knocking down the expression of NXPH4 via siRNA. In general, NXPH4 was predominantly upregulated in HCC tumors, and increased NXPH4 expression predicted unfavorable prognosis. The gene enrichment analysis displayed that NXPH4 was related with metabolic pathways. NXPH4 expression was correlated with immune cell infiltration. NXPH4 knockdown significantly suppressed proliferation, migration, and invasion of JHH7 and SNU182 cells. This study suggested that the upregulation of NXPH4 is associated with adverse prognosis and immune cell infiltration in HCC. NXPH4 could be a novel biomarker of unfavorable prognosis and an underlying target for immunotherapy in HCC.

High expression of NXPH4 correlates with poor prognosis, metabolic reprogramming, and immune infiltration in colon adenocarcinoma

“…Emerging evidence highlights the role of immune cell infiltration in the development, metastasis, and antitumor therapies of COAD ( 55 ). NXPH4 has been reported to play a role for the immune infiltration in bladder cancer ( 11 ) and hepatocellular carcinoma ( 14 ). Our analysis revealed that upregulated NXPH4 expression associates with increased infiltration of various immune cell types including NK cells, NK CD56bright cells, cytotoxic cells, macrophages, aDC cells, Th1 cells, neutrophils, and Treg cells in COAD.…”

“…Interestingly, recent studies have also implicated NXPH4 in the development and progression of several malignant tumors including bladder cancer ( 11 - 13 ), hepatocellular carcinoma ( 14 , 15 ), and non-small cell lung cancer ( 16 ). Additionally, it was reported that NXPH4 promotes gemcitabine resistance in bladder cancer ( 13 ).…”

NXPH4 can be used as a biomarker for pan-cancer and promotes colon cancer progression

“…The role of NXPH4 in cancer has only recently been investigated. NXPH4 shows a higher expression level in LIHC, BLCA, and non-small cell lung cancer [ 16 , 17 , 27 ], but the cause of NXPH4 dysregulation remains unclear. Our study also revealed a higher NXPH4 expression level in the transcriptome of most cancers.…”

“…However, further studies in peripheral blood are needed to translate the diagnostic potential of NXPH4 into clinical application, and NXPH4 also has the potential to serve as a prognostic marker. In BLCA and LIHC, NXPH4 was associated with a worse prognosis [ 17 , 27 ]. The findings of this research validate previous research and analyze the link between NXPH4 and OS, DSS, and PFS in pan-cancer.…”

Forkhead box protein K1‑regulated neurexophilin 4 promotes proliferation, metastasis and glycolysis in colorectal cancer

“…Neurexophilin 4 (NXPH4) is a synaptic secretory protein belonging to the NXPH family. Recent studies have revealed that NXPH4 is highly expressed in bladder cancer ( 6 ), liver cancer ( 7 ), breast cancer ( 8 ) and several other types of cancer. A previous study showed that NXPH4 knockdown can inhibit cell proliferation and migration, leading to significant cell cycle stagnation at the S1 stage in non-small cell lung cancer cells ( 9 ).…”