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: HSP90AB1

Gene summary for HSP90AB1

Gene summary.

Gene information	Species	Human
	Gene symbol	HSP90AB1
	Gene ID	3326
	Gene name	heat shock protein 90 alpha family class B member 1
	Gene Alias	D6S182
	Cytomap	6p21.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	A0A024RD80

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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
3326	HSP90AB1	CA_HPV_1	Human	Cervix	CC	7.82e-03	-2.45e-01	0.0264
3326	HSP90AB1	HSIL_HPV_2	Human	Cervix	HSIL_HPV	5.13e-34	-4.39e-01	0.0208
3326	HSP90AB1	N_HPV_2	Human	Cervix	N_HPV	1.12e-08	-6.29e-02	-0.0131
3326	HSP90AB1	CCI_1	Human	Cervix	CC	4.86e-35	-1.45e+00	0.528
3326	HSP90AB1	CCI_2	Human	Cervix	CC	2.59e-04	-3.79e-01	0.5249
3326	HSP90AB1	CCI_3	Human	Cervix	CC	4.09e-43	-1.48e+00	0.516
3326	HSP90AB1	CCII_1	Human	Cervix	CC	9.36e-56	-1.51e+00	0.3249
3326	HSP90AB1	Tumor	Human	Cervix	CC	7.16e-28	-3.73e-01	0.1241
3326	HSP90AB1	sample1	Human	Cervix	CC	2.32e-07	2.98e-01	0.0959
3326	HSP90AB1	sample3	Human	Cervix	CC	3.18e-55	-5.26e-01	0.1387
3326	HSP90AB1	H2	Human	Cervix	HSIL_HPV	3.14e-22	-4.57e-01	0.0632
3326	HSP90AB1	L1	Human	Cervix	CC	7.57e-10	-5.73e-01	0.0802
3326	HSP90AB1	T1	Human	Cervix	CC	4.88e-04	1.62e-01	0.0918
3326	HSP90AB1	T3	Human	Cervix	CC	1.37e-52	-5.31e-01	0.1389
3326	HSP90AB1	HTA11_3410_2000001011	Human	Colorectum	AD	1.62e-75	1.71e+00	0.0155
3326	HSP90AB1	HTA11_2487_2000001011	Human	Colorectum	SER	1.79e-38	1.84e+00	-0.1808
3326	HSP90AB1	HTA11_2951_2000001011	Human	Colorectum	AD	2.41e-23	1.70e+00	0.0216
3326	HSP90AB1	HTA11_1938_2000001011	Human	Colorectum	AD	1.44e-50	2.49e+00	-0.0811
3326	HSP90AB1	HTA11_78_2000001011	Human	Colorectum	AD	2.31e-47	2.05e+00	-0.1088
3326	HSP90AB1	HTA11_347_2000001011	Human	Colorectum	AD	2.72e-71	1.97e+00	-0.1954

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:0035303112	Skin	cSCC	regulation of dephosphorylation	49/4864	128/18723	1.46e-03	9.17e-03	49
GO:00713536	Skin	cSCC	cellular response to interleukin-4	17/4864	33/18723	1.50e-03	9.36e-03	17
GO:001631115	Skin	cSCC	dephosphorylation	134/4864	417/18723	2.65e-03	1.50e-02	134
GO:003367425	Skin	cSCC	positive regulation of kinase activity	148/4864	467/18723	3.00e-03	1.66e-02	148
GO:000717917	Skin	cSCC	transforming growth factor beta receptor signaling pathway	69/4864	198/18723	3.39e-03	1.84e-02	69
GO:004508812	Skin	cSCC	regulation of innate immune response	75/4864	218/18723	3.40e-03	1.84e-02	75
GO:0036363	Skin	cSCC	transforming growth factor beta activation	7/4864	10/18723	4.43e-03	2.29e-02	7
GO:00706706	Skin	cSCC	response to interleukin-4	17/4864	36/18723	4.85e-03	2.46e-02	17
GO:004586025	Skin	cSCC	positive regulation of protein kinase activity	123/4864	386/18723	5.23e-03	2.64e-02	123
GO:006156422	Skin	cSCC	axon development	146/4864	467/18723	5.50e-03	2.73e-02	146
GO:00607596	Skin	cSCC	regulation of response to cytokine stimulus	57/4864	162/18723	5.77e-03	2.85e-02	57
GO:006056023	Skin	cSCC	developmental growth involved in morphogenesis	78/4864	234/18723	7.08e-03	3.40e-02	78
GO:001820923	Skin	cSCC	peptidyl-serine modification	108/4864	338/18723	7.73e-03	3.60e-02	108
GO:004352319	Skin	cSCC	regulation of neuron apoptotic process	71/4864	212/18723	8.71e-03	4.01e-02	71
GO:199013823	Skin	cSCC	neuron projection extension	59/4864	172/18723	9.20e-03	4.20e-02	59
GO:00064576	Stomach	GC	protein folding	42/1159	212/18723	1.46e-11	3.31e-09	42
GO:00160326	Stomach	GC	viral process	58/1159	415/18723	4.75e-09	5.72e-07	58
GO:00190586	Stomach	GC	viral life cycle	48/1159	317/18723	7.84e-09	8.20e-07	48
GO:00094106	Stomach	GC	response to xenobiotic stimulus	61/1159	462/18723	1.68e-08	1.43e-06	61
GO:00458616	Stomach	GC	negative regulation of proteolysis	50/1159	351/18723	2.96e-08	2.33e-06	50

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0541820	Cervix	CC	Fluid shear stress and atherosclerosis	50/1267	139/8465	5.71e-10	1.32e-08	7.81e-09	50
hsa0461220	Cervix	CC	Antigen processing and presentation	34/1267	78/8465	1.06e-09	2.14e-08	1.26e-08	34
hsa0513220	Cervix	CC	Salmonella infection	74/1267	249/8465	1.33e-09	2.54e-08	1.50e-08	74
hsa0541720	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa0414120	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa0491520	Cervix	CC	Estrogen signaling pathway	44/1267	138/8465	3.55e-07	3.97e-06	2.35e-06	44
hsa0465718	Cervix	CC	IL-17 signaling pathway	31/1267	94/8465	8.71e-06	7.43e-05	4.39e-05	31
hsa052157	Cervix	CC	Prostate cancer	27/1267	97/8465	7.54e-04	3.39e-03	2.01e-03	27
hsa046596	Cervix	CC	Th17 cell differentiation	28/1267	108/8465	1.99e-03	7.98e-03	4.72e-03	28
hsa046213	Cervix	CC	NOD-like receptor signaling pathway	41/1267	186/8465	5.90e-03	1.95e-02	1.15e-02	41
hsa05418110	Cervix	CC	Fluid shear stress and atherosclerosis	50/1267	139/8465	5.71e-10	1.32e-08	7.81e-09	50
hsa04612110	Cervix	CC	Antigen processing and presentation	34/1267	78/8465	1.06e-09	2.14e-08	1.26e-08	34
hsa05132110	Cervix	CC	Salmonella infection	74/1267	249/8465	1.33e-09	2.54e-08	1.50e-08	74
hsa05417110	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa04141110	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa04915110	Cervix	CC	Estrogen signaling pathway	44/1267	138/8465	3.55e-07	3.97e-06	2.35e-06	44
hsa0465719	Cervix	CC	IL-17 signaling pathway	31/1267	94/8465	8.71e-06	7.43e-05	4.39e-05	31
hsa0521512	Cervix	CC	Prostate cancer	27/1267	97/8465	7.54e-04	3.39e-03	2.01e-03	27
hsa0465911	Cervix	CC	Th17 cell differentiation	28/1267	108/8465	1.99e-03	7.98e-03	4.72e-03	28
hsa0462112	Cervix	CC	NOD-like receptor signaling pathway	41/1267	186/8465	5.90e-03	1.95e-02	1.15e-02	41

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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

HSP90AB1

SNV

Missense_Mutation

c.1994C>G

p.Ser665Cys

p.S665C

P08238

protein_coding

deleterious(0.03)

benign(0.078)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HSP90AB1

SNV

Missense_Mutation

rs756933263

c.1655N>T

p.Lys552Met

p.K552M

P08238

protein_coding

deleterious(0.01)

probably_damaging(0.951)

TCGA-D8-A1Y1-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

HSP90AB1

SNV

Missense_Mutation

c.1367N>T

p.Arg456Leu

p.R456L

P08238

protein_coding

deleterious(0)

possibly_damaging(0.906)

TCGA-E2-A1IJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

HSP90AB1

SNV

Missense_Mutation

novel

c.748N>G

p.Ile250Val

p.I250V

P08238

protein_coding

tolerated(0.42)

benign(0)

TCGA-LL-A7T0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HSP90AB1

deletion

Frame_Shift_Del

novel

c.217_233delATTGACATCATCCCCAA

p.Ile73ProfsTer19

p.I73Pfs*19

P08238

protein_coding

TCGA-A8-A08O-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

HSP90AB1

SNV

Missense_Mutation

rs770945397

c.1346G>A

p.Arg449His

p.R449H

P08238

protein_coding

tolerated(0.07)

benign(0.003)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HSP90AB1

SNV

Missense_Mutation

c.87N>G

p.Ile29Met

p.I29M

P08238

protein_coding

deleterious(0.01)

possibly_damaging(0.863)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HSP90AB1

SNV

Missense_Mutation

c.52N>G

p.Gln18Glu

p.Q18E

P08238

protein_coding

deleterious(0.02)

possibly_damaging(0.48)

TCGA-VS-A958-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HSP90AB1

SNV

Missense_Mutation

c.52N>G

p.Gln18Glu

p.Q18E

P08238

protein_coding

deleterious(0.02)

possibly_damaging(0.48)

TCGA-ZJ-AAXU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HSP90AB1

SNV

Missense_Mutation

rs370988754

c.502C>T

p.Arg168Cys

p.R168C

P08238

protein_coding

deleterious(0.03)

benign(0.007)

TCGA-AA-3949-01

Colorectum

colon adenocarcinoma

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
3326	HSP90AB1	TRANSCRIPTION FACTOR, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, TUMOR SUPPRESSOR		ZERANOL	ZERANOL
3326	HSP90AB1	TRANSCRIPTION FACTOR, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, TUMOR SUPPRESSOR		ZEARALENONE	ZEARALENONE
3326	HSP90AB1	TRANSCRIPTION FACTOR, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, TUMOR SUPPRESSOR		RADANAMYCIN	RADANAMYCIN	16464590
3326	HSP90AB1	TRANSCRIPTION FACTOR, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, TUMOR SUPPRESSOR		GAMBOGIC ACID	GAMBOGIC ACID	21486005
3326	HSP90AB1	TRANSCRIPTION FACTOR, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, TUMOR SUPPRESSOR	inhibitor	AUY922
3326	HSP90AB1	TRANSCRIPTION FACTOR, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, TUMOR SUPPRESSOR		RHEIN	RHEIN
3326	HSP90AB1	TRANSCRIPTION FACTOR, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, TUMOR SUPPRESSOR	inhibitor	354702300	GELDANAMYCIN
3326	HSP90AB1	TRANSCRIPTION FACTOR, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, TUMOR SUPPRESSOR		IPI-504	RETASPIMYCIN HYDROCHLORIDE
3326	HSP90AB1	TRANSCRIPTION FACTOR, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, TUMOR SUPPRESSOR		MPC-3100
3326	HSP90AB1	TRANSCRIPTION FACTOR, DRUGGABLE GENOME, CLINICALLY ACTIONABLE, CELL SURFACE, TUMOR SUPPRESSOR		CELASTROL	CELASTROL	25756299,21129982

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