Supplementary Figures and Tables

Figure S1. The flowchart regarding the classification of the samples. The detailed operating procedures and information about classification of samples.

Figure S2. The results of the Fisher Ratio. Bar plot presented the interval of ‘ fisher ratio and the number of genes in each interval.

Figure S3. Screen plot of 300 representative genes. Scree plot was drawn to show the correlation between variance and the number of main components.

Figure S4. The bubble diagram of functional enrichment. The enriched Ontology for subtype 1, subtype 2 and subtype 3. Count means the number of genes enriched in a certain annotation.

Figure S5. The heatplot for the molecular subtypes, pathologic stage and TNM staging. Tnm_m, tnm_n and tnm_t were the TNM staging.

Table S1. The detailed information for the 34 DEGs. Gene Discription Reference p-Value Fold Change Symbol stage-specific differentially 3.368509 × GABRD expressed in hepatocellular [38] 34.8256 10−62 carcinoma 1.338193 × ANGPTL6 highly expressed in liver cancer [43] 0.1879 10−23 Required for mitochondrial 2.034419 × MSTO1 fusion and mitochondrial GeneCards 5.1055 10−94 network formation A potential therapeutic target of 3.463284 × EBF2 [40] 56.8254 HCC 10−49 9.070282 × GBA inhibit liver cancer [45] 4.0856 10−83 a valuable biomarker for the 2.854162 × CLEC4M prognosis of the patients with [30] 0.0273 10−14 HCC involved in tumor progression of 4.156083 × MIR3658 [52] 5.0915 bladder cancer 10−68 a therapeutic target for gastric 1.874503 × GPAA1 [51] 4.0789 cancer 10−70 highly expressed and associated 6.909608 × CACYBP [33] 3.3634 with poor prognosis in HCC 10−69 significant association with 3.449638 × SFTA1P [32] 123.5817 overall survival in HCC patients 10−48 linked with impaired liver 5.819188 × CXCL14 [49] 0.1507 function 10−20 represented a potential research 9.562192 × CKS1B target for therapeutics of [46] 3.7726 10−68 retinoblastoma 1.226416 × APLN played an oncogenic role in HCC [35] 24.4214 10−42 The gene is overexpressed in 8.404593 × KRTCAP2 GeneCards 3.4930 Liver 10−88 serve as a biomarker for 1.897959 × ESM1 diagnosing and monitoring renal [50] 29.5066 10−37 cell carcinoma The 2.562632 × TBCE Low tissue specificity 3.3832 Atlas 10−92 a signature gene highly associated 9.306855 × CLEC1B [47] 0.0368 with tumor progression 10−17 played a crucial role in the 8.340677 × PPOX [41] 3.5038 development of HCC 10−97 a potential noninvasive 7.580294 × CDH13 [36] 7.8091 biomarker of HCC 10−71 controls survival and 1.135516 × NTF3 differentiation of mammalian GeneCards 0.1380 10−22 neurons related to pathway Innate 9.410057 × C1orf35 GeneCards 3.9379 Immune System 10−86 correlated with overall survival in 5.074940 × C8orf33 [37] 3.7787 HCC patients 10−74 involved in post-transcriptional 2.573851 × MIR4793 regulation of in GeneCards 17.7375 10−44 multicellular organisms links to tumorigenesis and the 1.753135 × HIGD1B progression of pituitary GeneCards 13.1410 10−79 adenomas 1.733118 × BLOC1S3 induce hepatocyte apoptosis [44] 3.1598 10−74 LOC1053696 an RNA Gene, affiliated with the 1.855580 × GeneCards 4.5705 32 lncRNA class 10−69 Prognostic marker in liver cancer The Human 9.020337 × COL15A1 21.5720 (favourable) Protein Atlas 10−41 The Human 2.201642 × CRIP3 Cancer enhanced (liver cancer) 7.0812 Protein Atlas 10−35 promoted the tumor igenicity and 3.849815 × SMYD3 intrahepatic metastasis of HCC [39] 4.5849 10−46 cell played important role during 7.968983 × DDX11-AS1 [34] 12.1320 HCC oncogenesis 10−52 downregulated in HCC and could 2.130738 × CYP2C8 be a potential prognostic [31] 0.2245 10−20 biomarker the major microtubule-organizing 6.352548 × CEP72 GeneCards 4.2004 center in animal cells 10−48 an RNA Gene, and is affiliated 5.731509 × HCG25 GeneCards 5.1442 with the lncRNA class 10−59 expressed higher in HCC cells 1.191638 × FAM83H [48] 4.2419 compared to normal liver 10−63

Table S2. Function enrichment analysis of the 34 DEGs. Function p-Value Genes Receptor regulator activity 1.592 × 10−3 NTF3,CXCL14 Cell development 1.927 × 10−3 NTF3, TBCE, SMYD3 Positive regulation of response to external 2.429 × 10−3 NTF3, CDH13 stimulus NTF3,GBA,ANGPTL6, Multicellular organismal process 2.607 × 10−3 TBCE, CDH13 Muscle structure development 3.298 × 10−3 CXCL14, SMYD3 Viral genome replication 5.250 × 10−3 CLEC4M Membrane lipid catabolic process 5.250 × 10−3 GBA Cellular response to glucocorticoid stimulus 5.250 × 10−3 SMYD3 Modulation by virus of host morphology or 5.250 × 10−3 CLEC4M physiology Protein localization to microtubule organizing 5.250 × 10−3 CEP72 center Cellular response to dexamethasone stimulus 5.250 × 10−3 SMYD3 Skin morphogenesis 5.250 × 10−3 GBA Maintenance of protein localization in 5.250 × 10−3 GPAA1 endoplasmic reticulum Negative regulation of peptidyl-tyrosine 5.250 × 10−3 NTF3 phosphorylation Regulation of locomotion 5.405 × 10−3 NTF3, CDH13 regulation of the force of heart contraction 6.122 × 10−3 APLN Adhesion of symbiont to host 6.122 × 10−3 CLEC4M Muscle atrophy 6.122 × 10−3 TBCE Intracellular signal transduction 6.400 × 10−3 CLEC4M,NTF3, GBA NTF3,COL15A1,CLEC1B, Anatomical structure development 6.891 × 10−3 CXCL14 Pigment cell differentiation 6.993 × 10−3 BLOC1S3 Aromatase activity 6.993 × 10−3 CYP2C8 Oxygen binding 6.993 × 10−3 CYP2C8 GABA receptor activity 6.993 × 10−3 GABRD Response to testosterone 6.993 × 10−3 GBA Cell activation 7.107 × 10−3 CLEC1B, BLOC1S3 Cadherin binding 7.864 × 10−3 CDH13 Axo-dendritic transport 7.864 × 10−3 BLOC1S3 Phosphate-containing compound metabolic 8.058 × 10−3 NTF3,GBA,GPAA1 process Regulation of cyclin-dependent protein 8.734 × 10−3 CKS1B serine/threonine kinase activity Positive regulation of receptor-mediated 8.734 × 10−3 NTF3 endocytosis Extracellular matrix structural constituent 8.734 × 10−3 COL15A1 Endocrine hormone secretion 8.734 × 10−3 APLN FAM83H,CLEC1B, Developmental process 8.799 × 10−3 EBF2,BLOC1S3 Catalytic activity, acting on a protein 9.024 × 10−3 SMYD3,GPAA1,CKS1B Positive regulation of transport 9.557 × 10−3 NTF3, APLN Chemokine receptor binding 9.604 × 10−3 CXCL14 Porphyrin-containing compound metabolic 9.604 × 10−3 PPOX process

Table S3. Pathway enrichment analysis of the 34 DEGs. Pathway P-Value Genes C-type lectin receptor signaling pathway 3.9220 × 10−3 CLEC4M, CLEC1B Other glycan degradation 1.6532 × 10−2 GBA Glycosylphosphatidylinositol (GPI)-anchor 2.2556 × 10−2 GPAA1 biosynthesis Linoleic acid metabolism 2.5981 × 10−2 CYP2C8 Nicotine addiction 3.5343 × 10−2 GABRD Neuroactive ligand-receptor interaction 3.5760 × 10−2 GABRD, APLN CYP2C8,GBA, PPOX, Metabolic pathways 3.6029 × 10−2 GPAA1 Porphyrin and chlorophyll metabolism 3.7036 × 10−2 PPOX Sphingolipid metabolism 4.1255 × 10−2 GBA Arachidonic acid metabolism 5.4635 × 10−2 CYP2C8 Retinol metabolism 5.7952 × 10−2 CYP2C8 Drug metabolism - cytochrome P450 6.2082 × 10−2 CYP2C8 Chemical carcinogenesis 7.0290 × 10−2 CYP2C8 GABAergic synapse 7.5993 × 10−2 GABRD Protein digestion and absorption 7.6805 × 10−2 COL15A1 Morphine addiction 7.7617 × 10−2 GABRD Small cell lung cancer 7.9237 × 10−2 CKS1B Viral protein interaction with cytokine and 8.4888 × 10−2 CXCL14 cytokine receptor Serotonergic synapse 9.6883 × 10−2 CYP2C8