The Prognostic Significance and Potential Mechanism of Prolyl 3-Hydroxylase 1 in Hepatocellular Carcinoma

Prolyl 3-hydroxylase 1 (P3H1) is essential for human collagen synthesis. Here, we investigated its relevance to multiple cancers, especially hepatocellular carcinoma (LIHC).

We estimated the relationship of P3H1 with 33 cancers using publicly available databases. And immunohistochemistry was utilized to verify the P3H1 expression in liver, gastric, colon, pancreatic, and rectal cancer. Then, we attenuated P3H1 expression in BEL-7402 and HLF cells by lentivirus technology and assessed the effect of P3H1 on cell proliferation, migration, and invasion.

Bioinformatic analysis revealed a significantly higher expression of P3H1 in almost all tumors, which was consistent with the immunohistochemical findings in the liver, gastric, colon, pancreatic, and rectal cancers. P3H1 expression was associated with overall survival, progression-free interval, disease-specific survival, and disease-free interval in most cancers, particularly in LIHC. Besides, we also found that P3H1 expression was an independent prognostic factor for LIHC. And knockdown of P3H1 significantly reduced liver cancer cell proliferation, migration, and invasion in liver cancer cells. Interestingly, P3H1 expression levels showed a significant positive connection with Th2 infiltration through multiple immune infiltration algorithms. ICI treatment was less effective in LIHC patients with high P3H1 expression. Finally, we also identified an upstream regulatory mechanism of P3H1 in LIHC, namely, AL355488.1, HCG18, and THUMPD3-AS1/hsa-miR-29c-3p-P3H1 axis.

We have systematically described for the first time that P3H1 is closely related to various tumors, particularly in LIHC, and interference with P3H1 may be a therapeutic target for patients with LIHC.