Promising key genes associated with tumor microenvironments and prognosis of hepatocellular carcinoma

Table 1 Genes with significant prognostic value in hepatocellular carcinoma identified in both The Cancer Genome Atlas and Integrative Molecular Database of Hepatocellular Carcinoma

Times of gene verification by HCC cohorts from HCCDB	Down-regulated gene in low score group	Up-regulated gene in low score group
2	MS4A1, KLRB1, ITK, GZMH, ADH1C, UGT2B15, GPR171, CD40LG, CD5, FBLN2, CCL21, ATP2A3, IL16, ELN
1	SELL, CD5L, KLRK1, CXCR6, TRAF3IP3, CD79A, FLT3, GZMA, SPN, PRKCQ, SIDT1, RERGL, INMT, C11orf21, ZAP70, FLI1, DOK5, ITM2A, PHLDA3, APLNR, CFHR3, NLRC3, GIMAP1, FBLN5, DARC, SLFN12L, RASGRP2, SELP, ACAP1, C7, HTR2B, TNXB, SAMD3, PDZD4	CTSL2, MFAP2, TMC5, BACE2

Genes in bold have not been previously reported for their prognostic value in hepatocellular carcinoma patients. HCC: Hepatocellular carcinoma; HCCDB: Integrative molecular database of hepatocellular carcinoma.

Table 2 Top 10 genes predicting overall survival screened by lasso regression in hepatocellular carcinoma cohort from The Cancer Genome Atlas

Gene	Univariate Cox regression analysis			LASSO coefficient
	HR	95%CI	P value
NLRC3	0.72	0.60-0.87	0.0008	-0.0780
CFHR3	0.89	0.84-0.94	0.0001	-0.0375
KLRB1	0.84	0.76-0.93	0.0008	-0.0276
CTSL2	1.13	1.05-1.21	0.0005	0.0173
ADH1C	0.91	0.87-0.96	0.0002	-0.0149
CD5L	0.90	0.85-0.95	0.0004	-0.0131
TMC5	1.06	1.01-1.12	0.0255	0.0106
DOK5	0.84	0.75-0.95	0.0041	-0.0082
UGT2B15	0.91	0.86-0.96	0.0007	-0.0072
RASGRP2	0.82	0.72-0.93	0.0016	-0.0062

HR: Hazard ratio; CI: Confidential interval.

Table 3 Univariate and multivariate Cox regression analyese of prognostic factors and overall survival of patients with hepatocellular carcinoma from The Cancer Genome Atlas database

Variable	Univariate analysis			Multivariate analysis
	HR	95%CI	P value	HR	95%CI	P value
Risk score	11.37	5.49-23.56	< 0.001	8.99	2.53-32.01	0.001
TNM stage	1.79	1.45-2.22	< 0.001	1.24	0.89-1.75	0.209
Age	1.01	0.99-1.02	0.254
Gender	0.79	0.55-1.13	0.192
Race	1.13	0.94-1.37	0.196
Child-Pugh score	1.69	0.93-3.07	0.084
ECGO performance status	2.41	1.91-3.04	< 0.001	1.74	1.16-2.63	0.008
AFP	1	1-1	0.443
Fibrosis ishak score	0.91	0.78-1.07	0.253
Histologic grade	1.1	0.86-1.4	0.445
Vascular invasion	1.47	1.06-2.06	0.022	1.16	0.75-1.79	0.511
Hepatitis virus infection	0.45	0.3-0.68	< 0.001	0.81	0.45-1.46	0.477
Alcohol consumption	1.1	0.75-1.62	0.616

HR: Hazard ratio; CI: Confidential interval; ECOG: Eastern Cooperative Oncology Group.