<p>Development and Verification of the Hypoxia-Related and Immune-Associated Prognosis Signature for Hepatocellular Carcinoma</p>

Abstract

Background It has been widely suggested that the association of hypoxia with the immune status within the microenvironment of hepatocellular carcinoma (HCC) is of great clinical significance. The present work was carried out aiming to establish the hypoxia-related and immune-associated gene signature to stratify the risks in HCC. Patients and Methods The ssGSEA and t-SNE algorithms were utilized to estimate the immune and hypoxia statuses, respectively, using the TCGA database-derived cohort transcriptome profiles. Different immune groups are distinguished according to the ssGSEA scores, while the hypoxia-high and -low groups are inferred based on the distinct overall survival (OS) of the two groups of patients. Moreover, prognostic genes were identified using the Cox regression model in combination with the LASSO approach, which were later used to establish the hypoxia-related and immune-associated gene signature. At the same time, an ICGC cohort was used for external validation. Results A total of 13 genes, namely, HAVCR1, PSRC1, CCNJL, PDSS1, MEX3A, EID3, EPO, PLOD2, KPNA2, CDCA8, ADAMTS5, SLC1A7 and PIGZ , were discovered by the LASSO approach for constructing a gene signature to stratify the risk of HCC. Those low-risk cases showed superior prognosis (OS) to the high-risk counterparts (p<0.05). Moreover, it was suggested by multivariate analysis that our constructed hypoxia-related and immune-associated prognosis signature might be used as the independent factor for prognosis prediction (p<0.001). Patients in high-risk groups had severe hypoxia, higher immune checkpoint expression such as PD-L1, and different immunocyte infiltration states (eg, higher infiltration of regulatory T cells in the high-risk group) compared with those low-risk patients. Conclusion Our as-constructed hypoxia-related and immune-associated prognosis signature can be used as an approach to stratify the risk of HCC.

Structural variants in Chinese population and their impact on phenotypes, diseases and population adaptation

“…5d ), which illustrated the genetic diversity among individuals, suggesting that accumulation and combination of different genotypes of IGH genes might be associated with the immunity adaption to diverse environments. In addition, a 477 bp DEL was observed in intron of SLC1A7 , which is a solute carrier family member and has L-glutamate transmembrane transporter activity and was previously reported to be the immune-associated prognosis signature for hepatocellular carcinoma 39 . The differentiation of SVs in the immunity associated regions might be due to genetic drift and long-term expose to diverse environments for sub-populations of Chinese.…”

The REASON score: an epigenetic and clinicopathologic score to predict risk of poor survival in patients with early stage oral squamous cell carcinoma

“…RNF216 expression is associated with poor survival in colorectal cancer and ovarian carcinoma, although whether over- or under-expression decreases survival is unknown [ 51 , 52 ]. CCNJL expression is inversely correlated with survival in hepatocellular carcinoma [ 53 ]. Of note, differential methylation of the 12 genes has not previously been linked to poor survival in any type of cancer.…”

Prognostic significance of hypoxic and metabolic gene profiling in hepatocellular carcinoma

“…The Cox proportional hazards model was used to identify risk factors for mortality. Candidate risk factors for mortality were the different signatures evaluated for comparison [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] vs. the transcriptomic signature. 5 The PASW Statistics 26 program (IBM Corp.) was used for statistical analyses.…”

“…Hu et al 14 have described a hypoxia-related prognostic signature for HCC. Among 13 genes, PSRC1, MEX3A, PLOD2, KPNA2 and CDCA8 were upregulated in aggressive HCC (Table 2).…”