Abstract
Background The homeobox (HOX) gene family has been found to be involved in human cancers. However, its involvement in hepatocellular carcinoma (HCC) has not been well documented. Here, we comprehensively evaluated the role of HOXs in HCC. Methods RNA sequencing profile of TCGA-LIHC and LIRI-JP were obtained from the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), respectively. Data of TCGA-LIHC methylation were downloaded from UCSC Xena. Genetic alteration data for the TCGA samples was obtained from cBioPortal and GSCA. The diagnostic efficiency was assessed using ROC curves. The prognostic significance was evaluated by the Kaplan–Meier method and Cox regression analysis. Subsequent functional analysis was performed through the clusterProfiler package. ssGSEA, ESTIMATE, and TIDE algorithms were employed to explore the relationship between HOXs and the HCC microenvironment. Finally, pRRophetic package and NCI-60 cancerous cell lines were applied to estimate anticancer drug sensitivity. Results The mRNA levels of HOXs in HCC tissues were higher than those of noncancerous tissues and were correlated with poor overall survival (OS). HOXA6, C6, D9, D10, and D13 could serve as independent risk factors for OS. Further functional analysis revealed that these five HOXs regulate the cell proliferation, cell cycle, immune response, and microenvironment composition of HCC. In addition, the aberrant expression and methylation of HOXs is of great value in the diagnosis of HCC. Conclusion HOXs play crucial roles in HCC and could serve as potential markers for HCC diagnosis and prognosis.
Highlights
Hepatocellular carcinoma is an important cause of human cancer-related deaths worldwide, and its incidence continues to rise [1]
Even in patients with early hepatocellular carcinoma (HCC), the 5-year recurrence rate was close to 70% [3]. e high recurrence rate and poor curative effect are related to the complicated pathogenesis of HCC, as various networks of molecules and signaling pathways are involved in its occurrence and development [4]. erefore, the discovery of new molecules involved in HCC progression and the identification of new diagnostic markers and therapeutic targets is critically important for improving HCC patients’ prognosis
We first compared the transcriptional expression of HOXs in 374 HCC and 50 noncancerous samples from the Cancer Genome Atlas (TCGA)-LIHC (Figure 2(a)). e result showed that the mRNA levels of HOXs were generally higher in HCC. en, we analyzed the differences between 243 HCC and 202 noncancerous samples from the LIRI-JP cohort
Summary
Hepatocellular carcinoma is an important cause of human cancer-related deaths worldwide, and its incidence continues to rise [1]. We integrally analyzed the genomic data of HOXs in HCC, and assessed their diagnostic and prognostic value. Based on genes significantly correlated with HOXs, we constructed a PPI network using STRING v.10.0b (https://string-db.org/) [24]. E abundance of 24 immune cell types was predicted by calculating the single-sample gene set enrichment analysis (ssGSEA) scores based on the gene set signatures of each type of the immune cells through ImmuCellAI (http://bioinfo.life.hust.edu.cn/ImmuCellAI/ #!/) [27]. We obtained bubble plots presenting the correlation between the mRNA expression of the HOX genes and the estimated abundance of immune cells from the GSCA database. Afterwards, the stromal cell levels in HCC tissues were estimated using the ESTIMATE algorithm, which analyzes the composition of the microenvironment and calculates the tumor purity based on the gene expression data [29]. A P value
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
