SCL/TAL1 interrupting locus has been thought to be an oncogenic factor and its expression is up-regulated in many types of malignancies. However, there is no report on its role in the progression of HCC. In this study, we found that STIL expression is a robust prognostic predictor of HCC.
On the current study, we firstly evaluated the expression levels of STIL and observed that TUBG1 was abnormally expressed in various tumors including HCC. The result in HCC had been verified in multiple databases. In conclusion, STIL is overexpressed in HCC and further studies are necessary to reveal the mechanism of STIL of HCC.
Moreover, overexpression of STIL correlated to poor prognosis and poor clinicopathologic factors in HCC. Our study indicated that high expression of STIL was closely related to poor OS, DSS and PFI in HCC patients. In addition, we established a nomogram including STIL and T stage based on multivariate analysis. Calibration plot was used to verify the nomogram and demonstrated that prediction by the nomogram was consistent with actual observation for the probability of 1-,3-,5-year OS, with the C-indexes of 0.641 (95% CI: 0.614–0.668). Thus, our model could be a novel approach to evaluate prognosis of HCC patients.
To better explore the biological function of STIL in HCC patients, GO and KEGG functional enrichment analysis demonstrated that most enriched GO terms of the co-expressed genes were “chromosome segregation”, “DNA replication” and “nuclear division”. KEGG pathways, such as “DNA replication”, “spliceosome” and “cell cycle”. It is well‑known that defects in cell cycle regulation, such as sustaining proliferation and unlimited replication, are fundamental characteristics of cancer pathogenesis, and some newly discovered TNBC‑associated small molecule inhibitors have been demonstrated to induce cell cycle arrest . Similarly, chromosome segregation with nuclear division in M phase and DNA replication in S phase are essential processes during mitotic cell division. In tumorigenesis, driven by oncogene activation, DNA replication stress and its adverse impact on chromosome segregation are associated with genome instability. Furthermore, oocyte meiosis and progesterone‑mediated oocyte maturation pathways are enriched in survival associated miRNAs of ovarian carcinomas. Taken together, the results of our study indicated that STIL might modulate DNA replication and cell cycle to promote the occurrence and development of HCC. However, to better understand the role of STIL in HCC, further research of molecular regulatory mechanism was needed.
Recently, research studies have revealed that the interactions between immune cells and tumor are very important for tumor progression. Furthermore, potential clonal amplification and preferential enrichment of TIICs are present in HCC, and poor prognosis associated with TIICs accumulation in HCC . Our study showed that expression level of STIL was negatively correlated with a variety of immune cells, such as cytotoxic cells and dendritic cells (DCs, iDCs, and pDCs). DCs, known as antigen-presenting cells, play an important role in the initiation and regulation of tumor immune response. Recently, anti-cancer effect of DCs has been reported in HCC. Immature DCs have the function of phagocytosis. However, mature DCs have important regulatory functions and produce and secrete lots of cytokines. Moreover, cytotoxic cells, also known as CD8+T lymphocytes with cytotoxic granules, are the important anti-tumor effector cells. A research study has shown that hepatocellular carcinoma cell inhibited the cytotoxic T cells response to modulate tumor progression and tolerance to PD1 therapy. Furthermore, the expression of STIL was also closely related to T helper cells, Th2 cells, and Tfh in HCC. In conclusion, our results demonstrated that the STIL plays an important role in modulation of immune infiltrating cells in HCC.
However, this study had several limitations that should be considered. Firstly, we could not obtain all types of clinical information in public database, such as the approach of treatment for each patient, to better analysis the role of STIL in progression of HCC. Second, expansion of the clinical sample size is needed to validate the relationship between the expression of STIL and prognosis. Finally, in order to better explore the mechanism of STIL in HCC, we would carry out experimental research on STIL in the sooner future.