Association of Specificity Proteins with Hepatocellular Carcinoma Patients Survival

Presenter: Nwamaka Amy C. Iloani Authors: Nwamaka Iloani, Victoria Dulemba, Areeba Hafeez, Serena Bao and Riyaz Basha Title: Association of Specificity Proteins with Hepatocellular Carcinoma Patients Survival Background: Liver cancer is one of the most diagnosed cancers worldwide and ranks third in cancer mortality, leading to over 700,000 deaths per year. Of these liver cancers, the most common is hepatocellular carcinoma (HCC), accounting for nearly 80% of all liver cancer diagnoses. Since the current treatment options have limited improvement in prognosis over the years, identifying novel targets to induce therapeutic efficacy and reduce resistance to current therapeutic option is urgently needed. Specificity protein (Sp) transcription factors Sp1 and Sp3 are associated with incidences and poor prognosis of several cancers. Sp1 is implicated in the development and metastasis of HCC by binding to GC-rich sequences of the promoter region. Sp1 influences genetic transcription of the oncogenes encoding for the HCC by binding to gene regions such as RING1 and YY1 Binding Protein (RYBP), Ras guanine nucleotide-releasing protein 1 (RasGRP1) and many others to regulate their genetic expression. Sp3 works in a similar fashion and binds to GC and GT rich sequences in regulatory genes to affect HCC cell expression. The objective of this study is to ascertain the association of Sp1 and Sp3 expression with the survival of HCC patients using publicly available data bases. Method: Information regarding the expression levels of Sp1, Sp3, RYBP, RasGRP1 and Kaplain-Meier curves were obtained from accessing the data in the public data basses, R2 genomics visualization platform and The Cancer Genome Atlas (TCG). These data used to assess the probabilities of HCC patients with high vs low expression of Sp1 or Sp3. Results: The analysis of these data indicated significant findings. When comparing normal liver cell lines and HCC cell lines, HCC cell lines showed increased expression of both Sp1 and Sp3. The high expression of Sp1 or Sp3 is associated with decreased probability and chance of survival in comparison to individuals with decreased expression (Sp1: p< 0.027; Sp3: p< 0.0087). The survival curves of RYBP and RasGRP1 also following similar patten, however the relevance to Sp1 and Sp3 has higher impact and poor prognosis. Conclusion: Higher expressions of Sp1 and Sp3 are typically associated with poorer patient survival rates. These results suggest that the therapeutic interventions that focus on targeting Sp1, Sp3 and their downstream mechanisms have the chance for impeding HCC tumorigenesis. We are investigating the association of Sp1 and Sp3 regulated oncogenes with HCC. Investigational agents with inhibitory effect against Sp1 and Sp3 are also currently being tested against HCC proliferation. Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number (R25HL125447). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.