Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: APOB

Gene summary for APOB

Gene summary.

Gene information	Species	Human
	Gene symbol	APOB
	Gene ID	338
	Gene name	apolipoprotein B
	Gene Alias	FCHL2
	Cytomap	2p24.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	P04114

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
338	APOB	NAFLD1	Human	Liver	NAFLD	1.00e-15	1.50e+00	-0.04
338	APOB	S41	Human	Liver	Cirrhotic	2.30e-21	1.26e+00	-0.0343
338	APOB	S42	Human	Liver	HCC	3.93e-18	1.40e+00	-0.0103
338	APOB	S43	Human	Liver	Cirrhotic	1.05e-56	1.41e+00	-0.0187
338	APOB	S44	Human	Liver	HCC	7.35e-17	1.41e+00	-0.0083
338	APOB	HCC1_Meng	Human	Liver	HCC	3.90e-68	1.10e+00	0.0246
338	APOB	HCC2_Meng	Human	Liver	HCC	3.85e-19	-6.23e-01	0.0107
338	APOB	cirrhotic1	Human	Liver	Cirrhotic	3.47e-15	-2.44e-01	0.0202
338	APOB	cirrhotic2	Human	Liver	Cirrhotic	1.83e-16	-2.04e-02	0.0201
338	APOB	cirrhotic3	Human	Liver	Cirrhotic	2.16e-02	-2.73e-01	0.0215
338	APOB	HCC1	Human	Liver	HCC	5.53e-43	8.67e+00	0.5336
338	APOB	HCC2	Human	Liver	HCC	5.36e-57	8.64e+00	0.5341
338	APOB	HCC5	Human	Liver	HCC	2.63e-27	6.30e+00	0.4932
338	APOB	Pt13.a	Human	Liver	HCC	3.43e-18	1.30e-01	0.021
338	APOB	Pt13.b	Human	Liver	HCC	6.31e-49	3.98e-01	0.0251
338	APOB	Pt13.c	Human	Liver	HCC	4.98e-04	3.55e-01	0.0076
338	APOB	Pt14.a	Human	Liver	HCC	4.23e-14	9.22e-01	0.0169
338	APOB	Pt14.b	Human	Liver	HCC	8.40e-18	4.51e-01	0.018
338	APOB	Pt14.d	Human	Liver	HCC	3.77e-21	2.58e-01	0.0143
338	APOB	S014	Human	Liver	HCC	2.28e-13	2.15e+00	0.2254

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:190136115	Oral cavity	OSCC	organic cyclic compound catabolic process	272/7305	495/18723	2.73e-13	1.36e-11	272
GO:005079220	Oral cavity	OSCC	regulation of viral process	109/7305	164/18723	8.95e-13	4.10e-11	109
GO:190390020	Oral cavity	OSCC	regulation of viral life cycle	97/7305	148/18723	5.34e-11	1.67e-09	97
GO:00516074	Oral cavity	OSCC	defense response to virus	154/7305	265/18723	1.96e-10	5.63e-09	154
GO:01405464	Oral cavity	OSCC	defense response to symbiont	154/7305	265/18723	1.96e-10	5.63e-09	154
GO:004506917	Oral cavity	OSCC	regulation of viral genome replication	62/7305	85/18723	2.14e-10	6.04e-09	62
GO:00028317	Oral cavity	OSCC	regulation of response to biotic stimulus	177/7305	327/18723	1.73e-08	3.43e-07	177
GO:00094511	Oral cavity	OSCC	RNA modification	95/7305	167/18723	2.05e-06	2.62e-05	95
GO:00450717	Oral cavity	OSCC	negative regulation of viral genome replication	38/7305	56/18723	1.15e-05	1.18e-04	38
GO:00485259	Oral cavity	OSCC	negative regulation of viral process	56/7305	92/18723	1.77e-05	1.72e-04	56
GO:000941018	Oral cavity	OSCC	response to xenobiotic stimulus	222/7305	462/18723	4.00e-05	3.48e-04	222
GO:19016573	Oral cavity	OSCC	glycosyl compound metabolic process	52/7305	88/18723	1.06e-04	7.84e-04	52
GO:00506883	Oral cavity	OSCC	regulation of defense response to virus	42/7305	69/18723	1.92e-04	1.29e-03	42
GO:19011361	Oral cavity	OSCC	carbohydrate derivative catabolic process	89/7305	172/18723	4.52e-04	2.73e-03	89
GO:00091162	Oral cavity	OSCC	nucleoside metabolic process	37/7305	62/18723	7.79e-04	4.23e-03	37
GO:00442826	Oral cavity	OSCC	small molecule catabolic process	174/7305	376/18723	2.25e-03	1.00e-02	174
GO:00725272	Oral cavity	OSCC	pyrimidine-containing compound metabolic process	44/7305	82/18723	4.95e-03	1.94e-02	44
GO:0050691	Oral cavity	OSCC	regulation of defense response to virus by host	24/7305	41/18723	8.81e-03	3.19e-02	24
GO:00396943	Oral cavity	OSCC	viral RNA genome replication	21/7305	35/18723	9.58e-03	3.40e-02	21
GO:0016032110	Oral cavity	LP	viral process	211/4623	415/18723	4.06e-31	3.18e-28	211

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa049796	Liver	NAFLD	Cholesterol metabolism	20/1043	51/8465	9.73e-07	4.56e-05	3.67e-05	20
hsa0541714	Liver	NAFLD	Lipid and atherosclerosis	42/1043	215/8465	1.46e-03	1.71e-02	1.38e-02	42
hsa0497911	Liver	NAFLD	Cholesterol metabolism	20/1043	51/8465	9.73e-07	4.56e-05	3.67e-05	20
hsa0541715	Liver	NAFLD	Lipid and atherosclerosis	42/1043	215/8465	1.46e-03	1.71e-02	1.38e-02	42
hsa049792	Liver	Cirrhotic	Cholesterol metabolism	30/2530	51/8465	1.59e-05	1.39e-04	8.60e-05	30
hsa0541722	Liver	Cirrhotic	Lipid and atherosclerosis	80/2530	215/8465	1.18e-02	3.81e-02	2.35e-02	80
hsa049793	Liver	Cirrhotic	Cholesterol metabolism	30/2530	51/8465	1.59e-05	1.39e-04	8.60e-05	30
hsa0541732	Liver	Cirrhotic	Lipid and atherosclerosis	80/2530	215/8465	1.18e-02	3.81e-02	2.35e-02	80
hsa049794	Liver	HCC	Cholesterol metabolism	41/4020	51/8465	1.33e-06	1.35e-05	7.49e-06	41
hsa049795	Liver	HCC	Cholesterol metabolism	41/4020	51/8465	1.33e-06	1.35e-05	7.49e-06	41
hsa0541712	Stomach	GC	Lipid and atherosclerosis	40/708	215/8465	1.01e-06	1.80e-05	1.27e-05	40
hsa04975	Stomach	GC	Fat digestion and absorption	14/708	43/8465	5.71e-06	8.30e-05	5.84e-05	14
hsa0541713	Stomach	GC	Lipid and atherosclerosis	40/708	215/8465	1.01e-06	1.80e-05	1.27e-05	40
hsa049751	Stomach	GC	Fat digestion and absorption	14/708	43/8465	5.71e-06	8.30e-05	5.84e-05	14
hsa0541710	Stomach	SIM	Lipid and atherosclerosis	34/465	215/8465	1.80e-08	4.20e-07	3.37e-07	34
hsa049752	Stomach	SIM	Fat digestion and absorption	12/465	43/8465	2.11e-06	3.05e-05	2.45e-05	12
hsa04979	Stomach	SIM	Cholesterol metabolism	8/465	51/8465	6.17e-03	3.83e-02	3.08e-02	8
hsa0541711	Stomach	SIM	Lipid and atherosclerosis	34/465	215/8465	1.80e-08	4.20e-07	3.37e-07	34
hsa049753	Stomach	SIM	Fat digestion and absorption	12/465	43/8465	2.11e-06	3.05e-05	2.45e-05	12
hsa049791	Stomach	SIM	Cholesterol metabolism	8/465	51/8465	6.17e-03	3.83e-02	3.08e-02	8

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

APOB

SNV

Missense_Mutation

novel

c.8392G>C

p.Glu2798Gln

p.E2798Q

P04114

protein_coding

tolerated(0.3)

benign(0.138)

TCGA-3C-AALI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Poly E

Complete Response

APOB

SNV

Missense_Mutation

novel

c.13546N>A

p.Glu4516Lys

p.E4516K

P04114

protein_coding

tolerated(0.1)

possibly_damaging(0.485)

TCGA-A2-A0CR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

APOB

SNV

Missense_Mutation

c.7482N>G

p.Asn2494Lys

p.N2494K

P04114

protein_coding

tolerated(0.35)

benign(0.031)

TCGA-A2-A25B-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

APOB

SNV

Missense_Mutation

rs371177562

c.12677C>T

p.Thr4226Met

p.T4226M

P04114

protein_coding

deleterious(0.04)

benign(0)

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

APOB

SNV

Missense_Mutation

c.10418N>T

p.Ala3473Val

p.A3473V

P04114

protein_coding

deleterious(0.05)

benign(0.047)

TCGA-A7-A3RF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

APOB

SNV

Missense_Mutation

c.8477N>G

p.Glu2826Gly

p.E2826G

P04114

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A8-A06T-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

APOB

SNV

Missense_Mutation

c.5615N>A

p.Ile1872Asn

p.I1872N

P04114

protein_coding

deleterious(0)

probably_damaging(0.913)

TCGA-A8-A08O-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

APOB

SNV

Missense_Mutation

c.12526N>A

p.Val4176Ile

p.V4176I

P04114

protein_coding

tolerated(1)

benign(0.001)

TCGA-A8-A09Q-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

APOB

SNV

Missense_Mutation

c.2266N>T

p.Leu756Phe

p.L756F

P04114

protein_coding

tolerated(0.72)

benign(0.001)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

APOB

SNV

Missense_Mutation

c.9739N>G

p.Gln3247Glu

p.Q3247E

P04114

protein_coding

tolerated(0.12)

benign(0.127)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID	Symbol	Category	Interaction Types	Drug Claim Name	Drug Name	PMIDs
338	APOB	DRUGGABLE GENOME, CLINICALLY ACTIONABLE		ETHANOL	ALCOHOL	8576634
338	APOB	DRUGGABLE GENOME, CLINICALLY ACTIONABLE		LOVASTATIN	LOVASTATIN	2351867,7662319,1588827
338	APOB	DRUGGABLE GENOME, CLINICALLY ACTIONABLE		LIGNAN		15671223
338	APOB	DRUGGABLE GENOME, CLINICALLY ACTIONABLE		TKM-APOB
338	APOB	DRUGGABLE GENOME, CLINICALLY ACTIONABLE		QUERCETIN	QUERCETIN	16149735
338	APOB	DRUGGABLE GENOME, CLINICALLY ACTIONABLE		lomitapide	LOMITAPIDE
338	APOB	DRUGGABLE GENOME, CLINICALLY ACTIONABLE		EPIGALLOCATECHIN GALLATE		11936850
338	APOB	DRUGGABLE GENOME, CLINICALLY ACTIONABLE		PRAVASTATIN	PRAVASTATIN	8312689
338	APOB	DRUGGABLE GENOME, CLINICALLY ACTIONABLE		warfarin	WARFARIN
338	APOB	DRUGGABLE GENOME, CLINICALLY ACTIONABLE		DEXAMETHASONE	DEXAMETHASONE	7670964

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