Hepatocellular carcinoma: An analysis of the expression status of stress granules and their prognostic value

Table 1 Baseline clinical characteristics

ID	Dataset	Platforms	Sample	Source types	Ref.
1	TCGA-LIHC	-	50 HC, 374 HCC	Liver tissue	-
2	GSE25097	GPL10687	289 HC, 268 HCC	Liver tissue	[17-22]
3	GSE36376	GPL10588	433 HCC	Liver tissue	[23-25]

TCGA-LIHC: The Cancer Genome Atlas-Liver Hepatocellular Carcinoma; HCC: Hepatocellular carcinoma; HC: Healthy control.

Table 2 Hubgenes screened by Least absolute shrinkage and selection operator with coefficients

ID	coef	HR	HR (95L)	HR (95H)	P value
DDX1	1.109698909	3.033444913	1.220924802	7.536736107	0.01685573
DKC1	0.624264345	1.866872079	0.966659311	3.605418495	0.063029058
BICC1	-0.489537897	0.612909556	0.431027993	0.87153997	0.006421535
HNRNPUL1	-2.330604694	0.097236931	0.034257958	0.275994874	1.19E-05
CNOT6	1.986647774	7.291051498	2.746308357	19.35668725	6.67E-05
DYRK3	0.584581122	1.794239261	0.975801337	3.299129036	0.059953298
CCDC124	0.635540329	1.88804203	0.99423886	3.58535846	0.052100047

HR: Hazard ratio.

Table 3 Gene Ontology analysis results

Ontology	ID	Description	Gene ratio	Bg ratio	P value	adj P value
BP	GO:0006417	Regulation of translation	46/93	463/18800	3.06e-49	2.93e-46
BP	GO:1903311	Regulation of mRNA metabolic process	31/93	294/18800	3.99e-33	1.91e-30
BP	GO:0006401	RNA catabolic process	29/93	280/18800	1.06e-30	3.39e-28
BP	GO:0006402	mRNA catabolic process	27/93	233/18800	6.75e-30	1.62e-27
BP	GO:0017148	Negative regulation of translation	27/93	248/18800	3.81e-29	7.3e-27
CC	GO:0035770	Ribonucleoprotein granule	44/95	261/19594	9.7e-58	1.16e-55
CC	GO:0036464	Cytoplasmic ribonucleoprotein granule	40/95	243/19594	1.09e-51	6.51e-50
CC	GO:0010494	Cytoplasmic stress granule	23/95	79/19594	1.3e-35	5.21e-34
CC	GO:0000932	P-body	16/95	93/19594	6.99e-21	2.1e-19
CC	GO:0016281	Eukaryotic translation initiation factor 4F complex	7/95	11/19594	1.63e-14	3.92e-13
MF	GO:0008135	Translation factor activity, RNA binding	16/95	84/18410	3.24e-21	3.23e-19
MF	GO:0003743	Translation initiation factor activity	14/95	51/18410	3.87e-21	3.23e-19
MF	GO:0090079	Translation regulator activity, nucleic acid binding	17/95	108/18410	5.48e-21	3.23e-19
MF	GO:0045182	Translation regulator activity	24/95	406/18410	4.16e-19	1.84e-17
MF	GO:0003730	mRNA 3’-UTR binding	18/95	222/18410	7.11e-17	2.52e-15

GO: Gene Ontology; BP: Biological process; CC: Cellular component; MF: Molecular function; UTR: Untranslated region.

Table 4 Kyoto Encyclopedia of Genes and Genomes analysis results

Ontology	ID	Description	Gene ratio	Bg ratio	P value	adj P value
KEGG	hsa03018	RNA degradation	10/47	79/8164	1.55e-11	6.69e-10
KEGG	hsa03040	Spliceosome	7/47	147/8164	1.83e-05	0.0004
KEGG	hsa03013	Nucleocytoplasmic transport	6/47	108/8164	3.22e-05	0.0005
KEGG	hsa03015	mRNA surveillance pathway	5/47	97/8164	0.0002	0.0024
KEGG	hsa05014	Amyotrophic lateral sclerosis	7/47	364/8164	0.0045	0.0349
KEGG	hsa05416	Viral myocarditis	3/47	60/8164	0.0049	0.0349

KEGG: Kyoto Encyclopedia of Genes and Genomes.

Table 5 Gene Set Enrichment Analysis results

ID	Description	Set size	Enrichment score	NES	P value	adj P value	Q values
KEGG_FATTY_ACID_METABOLISM	KEGG_FATTY_ACID_METABOLISM	34	0.71018864	3.228627657	1.00E-10	6.65E-09	4.53E-09
KEGG_RETINOL_METABOLISM	KEGG_RETINOL_METABOLISM	27	0.800774501	3.477938283	1.00E-10	6.65E-09	4.53E-09
KEGG_DRUG_METABOLISM_CYTOCHROME_P450	KEGG_DRUG_METABOLISM_CYTOCHROME_P450	35	0.696799368	3.236251677	2.13E-10	9.45E-09	6.43E-09
KEGG_PPAR_SIGNALING_PATHWAY	KEGG_PPAR_SIGNALING_PATHWAY	38	0.63438858	3.008127457	1.34E-09	4.44E-08	3.02E-08
KEGG_GLYCINE_SERINE_AND_THREONINE_METABOLISM	KEGG_GLYCINE_SERINE_AND_THREONINE_METABOLISM	20	0.794030134	3.009053132	7.28E-09	1.94E-07	1.32E-07
KEGG_STEROID_HORMONE_BIOSYNTHESIS	KEGG_STEROID_HORMONE_BIOSYNTHESIS	28	0.69286184	2.925063353	1.14E-08	2.52E-07	1.71E-07
KEGG_CELL_CYCLE	KEGG_CELL_CYCLE	63	-0.616156999	-1.947443161	4.85E-08	9.22E-07	6.27E-07
KEGG_BUTANOATE_METABOLISM	KEGG_BUTANOATE_METABOLISM	28	0.643803698	2.717953993	2.54E-07	4.22E-06	2.88E-06
KEGG_COMPLEMENT_AND_COAGULATION_CASCADES	KEGG_COMPLEMENT_AND_COAGULATION_CASCADES	47	0.53140243	2.615817223	3.37E-07	4.97E-06	3.39E-06
KEGG_TRYPTOPHAN_METABOLISM	KEGG_TRYPTOPHAN_METABOLISM	29	0.61199465	2.664359791	1.07E-06	1.43E-05	9.72E-06
KEGG_METABOLISM_OF_XENOBIOTICS_BY_CYTOCHROME_P450	KEGG_METABOLISM_OF_XENOBIOTICS_BY_CYTOCHROME_P450	35	0.551628438	2.562012164	3.01E-06	3.64E-05	2.48E-05
KEGG_BETA_ALANINE_METABOLISM	KEGG_BETA_ALANINE_METABOLISM	17	0.692581145	2.532317703	2.55E-05	0.000282589	0.000192344
KEGG_PEROXISOME	KEGG_PEROXISOME	38	0.464005438	2.200209055	6.76E-05	0.000691885	0.000470931
KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION	KEGG_VALINE_LEUCINE_AND_ISOLEUCINE_DEGRADATION	33	0.487548344	2.182626135	0.000121713	0.001156276	0.000787018
KEGG_ARACHIDONIC_ACID_METABOLISM	KEGG_ARACHIDONIC_ACID_METABOLISM	28	0.496563499	2.096348232	0.000261033	0.002314494	0.001575358
KEGG_PROPANOATE_METABOLISM	KEGG_PROPANOATE_METABOLISM	21	0.516414812	1.982973473	0.001656507	0.013769716	0.009372343
KEGG_TYROSINE_METABOLISM	KEGG_TYROSINE_METABOLISM	25	0.468326241	1.954109762	0.001866878	0.014605575	0.00994127
KEGG_ARGININE_AND_PROLINE_METABOLISM	KEGG_ARGININE_AND_PROLINE_METABOLISM	26	0.432080752	1.85908878	0.002731901	0.018388891	0.01251638
KEGG_SMALL_CELL_LUNG_CANCER	KEGG_SMALL_CELL_LUNG_CANCER	48	-0.516209717	-1.594193363	0.002759563	0.018388891	0.01251638
KEGG_OOCYTE_MEIOSIS	KEGG_OOCYTE_MEIOSIS	51	-0.503867568	-1.561948773	0.002765247	0.018388891	0.01251638

KEGG: Kyoto Encyclopedia of Genes and Genomes.

Table 6 Gene Set Variation Analysis results

	logFC	AveExpr	t	P value	adj P value	B
KEGG_RNA_DEGRADATION	0.26385	-0.0063	9.67948	6.21E-20	9.44E-18	34.57459
KEGG_DRUG_METABOLISM_CYTOCHROME_P450	-0.2879	0.02526	-7.7606	8.06E-14	6.12E-12	20.81127
KEGG_PPAR_SIGNALING_PATHWAY	-0.2706	0.04111	-7.3521	1.23E-12	4.36E-11	18.15604
KEGG_GLYCINE_SERINE_AND_THREONINE_METABOLISM	-0.3098	0.03838	-7.3347	1.38E-12	4.36E-11	18.04547
KEGG_CELL_CYCLE	0.21445	-0.0119	7.31519	1.56E-12	4.36E-11	17.92124
KEGG_STEROID_HORMONE_BIOSYNTHESIS	-0.258	0.03831	-7.2895	1.85E-12	4.36E-11	17.75812
KEGG_RETINOL_METABOLISM	-0.2937	0.04154	-7.277	2.01E-12	4.36E-11	17.67921
KEGG_MATURITY_ONSET_DIABETES_OF_THE_YOUNG	-0.2291	0.02587	-7.0965	6.41E-12	1.22E-10	16.54879
KEGG_SPLICEOSOME	0.23491	0.00117	6.77412	4.84E-11	8.17E-10	14.58431
KEGG_ARACHIDONIC_ACID_METABOLISM	-0.1958	0.0193	-6.5965	1.43E-10	2.03E-09	13.53201
KEGG_LINOLEIC_ACID_METABOLISM	-0.3017	0.04341	-6.5919	1.47E-10	2.03E-09	13.50512
KEGG_FATTY_ACID_METABOLISM	-0.278	0.02396	-6.5447	1.96E-10	2.48E-09	13.22943
KEGG_GLYCOLYSIS_GLUCONEOGENESIS	-0.1779	-0.007	-6.482	2.84E-10	3.33E-09	12.86608
KEGG_VASOPRESSIN_REGULATED_WATER_REABSORPTION	0.14008	-0.0067	6.40042	4.62E-10	5.01E-09	12.39671
KEGG_PROGESTERONE_MEDIATED_OOCYTE_MATURATION	0.14218	0.00097	6.26602	1.01E-09	9.71E-09	11.63418
KEGG_CALCIUM_SIGNALING_PATHWAY	-0.1189	0.00875	-6.2615	1.04E-09	9.71E-09	11.60868
KEGG_COMPLEMENT_AND_COAGULATION_CASCADES	-0.2481	0.03366	-6.2543	1.09E-09	9.71E-09	11.56852
KEGG_BASAL_TRANSCRIPTION_FACTORS	0.20569	-0.0133	6.20578	1.44E-09	1.18E-08	11.29665
KEGG_TYROSINE_METABOLISM	-0.2007	0.01699	-6.2017	1.47E-09	1.18E-08	11.27395
KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION	-0.1315	0.01542	-6.1916	1.56E-09	1.19E-08	11.21751

KEGG: Kyoto Encyclopedia of Genes and Genomes.

Table 7 Single variate Cox analysis of hub genes

ID	HR	HR (95L)	HR (95H)	P value
DDX1	2.811787564	1.79184186	4.412303052	6.89E-06
DKC1	2.088261011	1.488787267	2.929118315	2.00E-05
BICC1	1.203898304	1.01529958	1.427530509	0.032791365
HNRNPUL1	1.717777659	1.128350776	2.615108838	0.011631909
CNOT6	2.223105295	1.547745966	3.193157832	1.53E-05
DYRK3	1.970782211	1.324333062	2.932783779	0.000822902
CCDC124	1.951959781	1.340432388	2.84247607	0.000486868

HR: Hazard ratio.