P1795 - Identification of Three Up-Regulated Hub Genes as Potential Diagnostic Markers, Prognostic Markers, and Therapeutic Targets in Hepatocellular Carcinoma by Integrated Bioinformatic Analysis

Chenyu Sun, MD, MSc¹, Yue Chen, ², Tianming Zhao, ³, Shaodi Ma, ⁴, Na Hyun Kim, MD¹, John Pocholo W. Tuason, MD¹, Chandur Bhan, MD¹, Nikitha Manem, MD¹, Apurwa Prasad, MD¹, Mohamed R. Ismail, MBBCh¹, Ayesha Iftekhar, MD¹, Jie Liu, MD^5
1AMITA Health Saint Joseph Hospital, Chicago, IL; ²School of the First Clinical Medicine, Anhui Medical University, Hefei, Anhui, China; ³Anhui Medical University, Hefei, Anhui, China; ⁴School of Public Health, Anhui Medical University, Hefei, Anhui, China; ⁵The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China

Introduction: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. This study aimed to identify differentially expressed genes (DEGs) of HCC to identify potential biomarkers or therapeutic targets.


Methods: Two gene expression profiles (GSE84402 and GSE101685) were obtained from GEO database (Gene Expression Omnibus https://www.ncbi.nlm.nih.gov/geo/). DEGs between HCC and normal tissue specimen were identified via GEO2R online tools with |logFC| > 2 and adjust P value < 0.05. The DEGs with log FC > 2 were considered as an up-regulated gene. Then, the raw data were checked in Venn software online to detect the commonly DEGs among the two datasets. Next, a protein-protein interaction network (PPI) was constructed by Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software. Then cytoHubba app in Cytoscape was used to select the top three hub genes. Finally, to validate the study results, selected up-regulated hub genes were imported into ULCAN to implement survival analysis and validate the expression of hub genes. The best discriminate cut-off point between the high and low expression groups was assessed by the ROC curve and area under the curve (AUC) values for selected hub genes, based on data from The Cancer Genome Atlas (TCGA). R software by using pROC and ggplot2 packages were used.

Results: The top three up-regulated hub genes (highly expressed genes in HCC tissues: RRM2, BUB1B, and CDC20) were selected for further analysis. Analysis via ULCAN found that the expression level of RRM2, BUB1B, and CDC20 were all significantly elevated in tumor tissues than normal tissues. Survival analysis found they were all associated with poor overall survival. Further analysis of the ROC curve showed that the AUC of RRM, RUB1B, and CDC20 were 0.961, 0.962, and 0.979, respectively. Their positive predictive values (PPVs) were 0.988, 0.991, and 0.991, respectively.

Discussion: RRM2, BUB1B, and CDC20 could be potential diagnostic biomarkers, prognostic markers, and therapeutic targets of HCC. However, our results are needed to be further confirmed by experimental research in the future.



Disclosures:


Chenyu Sun, MD, MSc¹, Yue Chen, ², Tianming Zhao, ³, Shaodi Ma, ⁴, Na Hyun Kim, MD¹, John Pocholo W. Tuason, MD¹, Chandur Bhan, MD¹, Nikitha Manem, MD¹, Apurwa Prasad, MD¹, Mohamed R. Ismail, MBBCh¹, Ayesha Iftekhar, MD¹, Jie Liu, MD⁵. P1795 - Identification of Three Up-Regulated Hub Genes as Potential Diagnostic Markers, Prognostic Markers, and Therapeutic Targets in Hepatocellular Carcinoma by Integrated Bioinformatic Analysis, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.