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: HMGB1

Gene summary for HMGB1

Gene summary.

Gene information	Species	Human
	Gene symbol	HMGB1
	Gene ID	3146
	Gene name	high mobility group box 1
	Gene Alias	HMG-1
	Cytomap	13q12.3
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	A0A024RDR0

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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
3146	HMGB1	Dong_P5	Human	Prostate	Tumor	7.42e-05	2.22e-01	0.053
3146	HMGB1	P7	Human	Prostate	Tumor	2.93e-28	1.00e+00	-0.1025
3146	HMGB1	P9	Human	Prostate	Tumor	3.85e-02	-2.65e-01	-0.0285
3146	HMGB1	P10	Human	Prostate	Tumor	4.03e-12	6.30e-01	-0.0902
3146	HMGB1	GSM5353215_PA_AUG_PB_1B_S2	Human	Prostate	Tumor	2.03e-08	-8.85e-01	0.1557
3146	HMGB1	GSM5353216_PA_PB1A_Pool_1_3_S50_L002	Human	Prostate	Tumor	3.35e-08	-1.00e+00	0.159
3146	HMGB1	GSM5353217_PA_PB1A_Pool_2_S107_L004	Human	Prostate	Tumor	1.93e-08	-1.29e+00	0.156
3146	HMGB1	GSM5353218_PA_PB1B_Pool_1_2_S74_L003	Human	Prostate	Tumor	1.40e-05	-9.39e-01	0.1479
3146	HMGB1	GSM5353220_PA_PB1B_Pool_3_S51_L002	Human	Prostate	Tumor	8.58e-12	-1.15e+00	0.1531
3146	HMGB1	GSM5353221_PA_PB2A_Pool_1_3_S25_L001	Human	Prostate	Tumor	1.46e-25	-9.68e-01	0.1633
3146	HMGB1	GSM5353222_PA_PB2B_Pool_1_3_S52_L002	Human	Prostate	Tumor	1.56e-33	-9.59e-01	0.1608
3146	HMGB1	GSM5353223_PA_PB2B_Pool_2_S26_L001	Human	Prostate	Tumor	5.06e-18	-8.44e-01	0.1604
3146	HMGB1	GSM5353224_PA_PR5186_Pool_1_2_3_S27_L001	Human	Prostate	Tumor	6.03e-13	-6.55e-01	0.1621
3146	HMGB1	GSM5353225_PA_PR5196-1_Pool_1_2_3_S53_L002	Human	Prostate	Tumor	1.15e-13	-9.87e-01	0.1619
3146	HMGB1	GSM5353226_PA_PR5196-2_Pool_1_2_3_S54_L002	Human	Prostate	Tumor	5.41e-09	-9.72e-01	0.159
3146	HMGB1	GSM5353227_PA_PR5199-193K_Pool_1_2_3_S55_L002	Human	Prostate	Tumor	3.17e-28	-9.97e-01	0.1602
3146	HMGB1	GSM5353228_PA_PR5199-640K_Pool_1_3_S108_L004	Human	Prostate	Tumor	1.99e-09	-1.09e+00	0.1537
3146	HMGB1	GSM5353232_PA_PR5249_T1_S3_L001	Human	Prostate	Tumor	7.91e-18	-1.09e+00	0.1439
3146	HMGB1	GSM5353236_PA_PR5251_T1_S7_L001	Human	Prostate	Tumor	3.11e-18	-1.09e+00	0.1608
3146	HMGB1	GSM5353237_PA_PR5251_T2_S8_L001	Human	Prostate	Tumor	1.80e-07	-8.78e-01	0.1622

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗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:00060918	Breast	Precancer	generation of precursor metabolites and energy	94/1080	490/18723	1.54e-25	1.64e-22	94
GO:00159808	Breast	Precancer	energy derivation by oxidation of organic compounds	70/1080	318/18723	8.33e-23	6.37e-20	70
GO:00525479	Breast	Precancer	regulation of peptidase activity	71/1080	461/18723	2.72e-14	6.94e-12	71
GO:00525489	Breast	Precancer	regulation of endopeptidase activity	67/1080	432/18723	1.06e-13	2.36e-11	67
GO:20001169	Breast	Precancer	regulation of cysteine-type endopeptidase activity	43/1080	235/18723	1.30e-11	1.83e-09	43
GO:00432819	Breast	Precancer	regulation of cysteine-type endopeptidase activity involved in apoptotic process	40/1080	209/18723	1.59e-11	2.07e-09	40
GO:00485459	Breast	Precancer	response to steroid hormone	53/1080	339/18723	3.07e-11	3.66e-09	53
GO:00458629	Breast	Precancer	positive regulation of proteolysis	51/1080	372/18723	7.77e-09	5.70e-07	51
GO:00319608	Breast	Precancer	response to corticosteroid	30/1080	167/18723	2.50e-08	1.65e-06	30
GO:00109529	Breast	Precancer	positive regulation of peptidase activity	33/1080	197/18723	3.01e-08	1.89e-06	33
GO:00975297	Breast	Precancer	myeloid leukocyte migration	34/1080	220/18723	1.42e-07	7.82e-06	34
GO:00509006	Breast	Precancer	leukocyte migration	47/1080	369/18723	2.82e-07	1.39e-05	47
GO:00022629	Breast	Precancer	myeloid cell homeostasis	27/1080	157/18723	3.10e-07	1.49e-05	27
GO:00432808	Breast	Precancer	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	24/1080	129/18723	3.13e-07	1.50e-05	24
GO:00513848	Breast	Precancer	response to glucocorticoid	26/1080	148/18723	3.32e-07	1.57e-05	26
GO:00305956	Breast	Precancer	leukocyte chemotaxis	34/1080	230/18723	4.16e-07	1.89e-05	34
GO:00109509	Breast	Precancer	positive regulation of endopeptidase activity	29/1080	179/18723	4.23e-07	1.90e-05	29
GO:00457859	Breast	Precancer	positive regulation of cell adhesion	52/1080	437/18723	5.74e-07	2.49e-05	52
GO:00603266	Breast	Precancer	cell chemotaxis	41/1080	310/18723	5.99e-07	2.55e-05	41
GO:00511019	Breast	Precancer	regulation of DNA binding	22/1080	118/18723	9.28e-07	3.71e-05	22

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04140	Colorectum	AD	Autophagy - animal	49/2092	141/8465	4.58e-03	2.20e-02	1.40e-02	49
hsa041401	Colorectum	AD	Autophagy - animal	49/2092	141/8465	4.58e-03	2.20e-02	1.40e-02	49
hsa04217	Colorectum	SER	Necroptosis	47/1580	159/8465	5.21e-04	4.44e-03	3.22e-03	47
hsa041402	Colorectum	SER	Autophagy - animal	39/1580	141/8465	5.43e-03	3.28e-02	2.38e-02	39
hsa042171	Colorectum	SER	Necroptosis	47/1580	159/8465	5.21e-04	4.44e-03	3.22e-03	47
hsa041403	Colorectum	SER	Autophagy - animal	39/1580	141/8465	5.43e-03	3.28e-02	2.38e-02	39
hsa041404	Colorectum	MSS	Autophagy - animal	45/1875	141/8465	4.42e-03	1.90e-02	1.16e-02	45
hsa041405	Colorectum	MSS	Autophagy - animal	45/1875	141/8465	4.42e-03	1.90e-02	1.16e-02	45
hsa0414010	Esophagus	ESCC	Autophagy - animal	101/4205	141/8465	7.60e-08	6.21e-07	3.18e-07	101
hsa034104	Esophagus	ESCC	Base excision repair	38/4205	44/8465	3.59e-07	2.62e-06	1.34e-06	38
hsa0414015	Esophagus	ESCC	Autophagy - animal	101/4205	141/8465	7.60e-08	6.21e-07	3.18e-07	101
hsa0341011	Esophagus	ESCC	Base excision repair	38/4205	44/8465	3.59e-07	2.62e-06	1.34e-06	38
hsa041406	Liver	Cirrhotic	Autophagy - animal	65/2530	141/8465	3.10e-05	2.47e-04	1.52e-04	65
hsa0414011	Liver	Cirrhotic	Autophagy - animal	65/2530	141/8465	3.10e-05	2.47e-04	1.52e-04	65
hsa0414021	Liver	HCC	Autophagy - animal	99/4020	141/8465	3.08e-08	4.70e-07	2.61e-07	99
hsa0414031	Liver	HCC	Autophagy - animal	99/4020	141/8465	3.08e-08	4.70e-07	2.61e-07	99
hsa041409	Oral cavity	OSCC	Autophagy - animal	94/3704	141/8465	2.73e-08	2.38e-07	1.21e-07	94
hsa03410	Oral cavity	OSCC	Base excision repair	32/3704	44/8465	9.11e-05	3.25e-04	1.65e-04	32
hsa0414014	Oral cavity	OSCC	Autophagy - animal	94/3704	141/8465	2.73e-08	2.38e-07	1.21e-07	94
hsa034101	Oral cavity	OSCC	Base excision repair	32/3704	44/8465	9.11e-05	3.25e-04	1.65e-04	32

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
HMGB1	PVA	Liver	Cirrhotic	B2M,GNG11,PTMA, etc.	4.01e-01

∗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

HMGB1

SNV

Missense_Mutation

c.120N>C

p.Glu40Asp

p.E40D

P09429

protein_coding

deleterious(0.02)

benign(0.105)

TCGA-D8-A1XT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin+cyclophosphamide

HMGB1

SNV

Missense_Mutation

c.131A>C

p.Lys44Thr

p.K44T

P09429

protein_coding

deleterious(0.02)

possibly_damaging(0.784)

TCGA-A6-6780-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

HMGB1

SNV

Missense_Mutation

c.624A>T

p.Glu208Asp

p.E208D

P09429

protein_coding

tolerated_low_confidence(0.26)

benign(0)

TCGA-AA-3821-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

HMGB1

SNV

Missense_Mutation

c.443C>G

p.Ala148Gly

p.A148G

P09429

protein_coding

deleterious(0.01)

probably_damaging(0.983)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

HMGB1

SNV

Missense_Mutation

novel

c.377C>T

p.Ala126Val

p.A126V

P09429

protein_coding

deleterious(0.03)

benign(0.221)

TCGA-A5-A2K5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

HMGB1

SNV

Missense_Mutation

novel

c.168G>T

p.Glu56Asp

p.E56D

P09429

protein_coding

deleterious(0.04)

benign(0.105)

TCGA-AP-A1E0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

HMGB1

SNV

Missense_Mutation

c.253N>G

p.Thr85Ala

p.T85A

P09429

protein_coding

tolerated(0.15)

benign(0.009)

TCGA-B5-A11E-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

HMGB1

SNV

Missense_Mutation

novel

c.23N>G

p.Lys8Arg

p.K8R

P09429

protein_coding

deleterious(0.02)

benign(0.358)

TCGA-B5-A1MR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

HMGB1

SNV

Missense_Mutation

novel

c.25N>T

p.Pro9Ser

p.P9S

P09429

protein_coding

deleterious(0.04)

possibly_damaging(0.573)

TCGA-B5-A3FC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

HMGB1

SNV

Missense_Mutation

c.488G>A

p.Arg163Gln

p.R163Q

P09429

protein_coding

tolerated(0.16)

benign(0.193)

TCGA-BS-A0UV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

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
3146	HMGB1	DRUGGABLE GENOME, CELL SURFACE, TRANSCRIPTION FACTOR		PREDNISOLONE	PREDNISOLONE	18447956
3146	HMGB1	DRUGGABLE GENOME, CELL SURFACE, TRANSCRIPTION FACTOR		AUTOLOGOUS DENDRITIC CELLS		16997859
3146	HMGB1	DRUGGABLE GENOME, CELL SURFACE, TRANSCRIPTION FACTOR		ADJUVANT		15161015
3146	HMGB1	DRUGGABLE GENOME, CELL SURFACE, TRANSCRIPTION FACTOR		SALINE	SODIUM CHLORIDE	17334244
3146	HMGB1	DRUGGABLE GENOME, CELL SURFACE, TRANSCRIPTION FACTOR		DISTAMYCIN		9161031
3146	HMGB1	DRUGGABLE GENOME, CELL SURFACE, TRANSCRIPTION FACTOR		GP100		16968820
3146	HMGB1	DRUGGABLE GENOME, CELL SURFACE, TRANSCRIPTION FACTOR		CHLORAMPHENICOL	CHLORAMPHENICOL	9931456
3146	HMGB1	DRUGGABLE GENOME, CELL SURFACE, TRANSCRIPTION FACTOR		EGCG	EPIGALOCATECHIN GALLATE	17987129
3146	HMGB1	DRUGGABLE GENOME, CELL SURFACE, TRANSCRIPTION FACTOR		MART1		16968820
3146	HMGB1	DRUGGABLE GENOME, CELL SURFACE, TRANSCRIPTION FACTOR		AMPICILLIN	AMPICILLIN	9931456

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