In 2020, there were over 906,000 new cases and 830,000 deaths of primary liver cancer, and HCC accounts for 75–85% of all primary liver cancers[1]. The global burden of HCC is high, and the prognosis of HCC is poor, which is related to early invasion and metastasis[26]. MiRNAs are members of the RNA family and play a key role in proliferation, invasion, metastasis, and immune escape of HCC[27–30]. Therefore, it is necessary to establish a prognostic model that includes the expression of miRNAs molecules related to HCC prognosis.
In previous studies, miR-9-5p has been reported to play an important role in a variety of diseases. In cervical cancer, miR-9-5p promotes tumor angiogenesis by targeting SOCS[31]. In prostate cancer, mir-9-5p regulates the expression of QKI-5, StarD, and other genes, thus affecting tumor invasion and metastasis[32, 33]. However, Wang et al revealed that miR-9-5p inhibits tumor cell proliferation and promotes apoptosis by down-regulating PAK4 in colorectal cancer[34]. In HCC, several experimental studies have shown that miR-9-5p can promote the proliferation, invasion, and metastasis of tumor cells by down-regulating the expression of ESR1[35], Klf4[36], CNNM1[37], PPARA[38], and so on. In a previous study, high expression of miR-9-5p was associated with a poor prognosis of osteosarcoma[39]. However, patients with high expression of miR-9-5p are reported to have a better prognosis in ovarian cancer [40].
The present study focused on identifying miRNAs related to VI in HCC. Unlike other database-based studies[41–43], all the study subjects were HCC patients, to more accurately screen for differentially expressed miRNAs related to VI. Patients who met the inclusion criteria were divided into two groups based on whether or not they had VI, and the differences in miRNA expression levels analyzed. Seven differentially expressed miRNAs were identified, however, only miR-9-5p was highly expressed in HCC patients and correlated with OS. The potential targets of miR-9-5p were identified from three target gene prediction databases. GO and KEGG enrichment was used to predict the potential mechanism of miR-9-5p in HCC. PPI analysis was used to select the core target genes, and miR-9-5p was used in constructing a nomogram that had a significant prognostic value for predicting survival in HCC patients.
However, this study had some limitations. On the one hand, validation of the nomogram was not performed, due to lack of VI, survival, and miRNAs expression data using data from other databases. On the other hand, although many experimental studies have shown that miR-9-5p is related to the proliferation, invasion, and metastasis of HCC, the relationship between miR-9-5p expression and VI of HCC needs further experimental studies.
In conclusion, miR-9-5p is associated with VI in HCC and can be used as a potential diagnostic and prognostic signature for predicting the overall survival of HCC patients.