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: HSP90AA1

Gene summary for HSP90AA1

Gene summary.

Gene information	Species	Human
	Gene symbol	HSP90AA1
	Gene ID	3320
	Gene name	heat shock protein 90 alpha family class A member 1
	Gene Alias	EL52
	Cytomap	14q32.31
	Gene Type	protein-coding
	GO ID	GO:0000723
	UniProtAcc	P07900

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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
3320	HSP90AA1	GSM4909277	Human	Breast	Precancer	7.31e-03	4.80e-01	0.0177
3320	HSP90AA1	GSM4909282	Human	Breast	IDC	7.28e-03	-2.11e-01	-0.0288
3320	HSP90AA1	GSM4909286	Human	Breast	IDC	2.42e-20	-3.66e-01	0.1081
3320	HSP90AA1	GSM4909291	Human	Breast	IDC	3.71e-11	3.63e-01	0.1753
3320	HSP90AA1	GSM4909293	Human	Breast	IDC	1.00e-07	-1.71e-01	0.1581
3320	HSP90AA1	GSM4909294	Human	Breast	IDC	3.63e-11	1.56e-01	0.2022
3320	HSP90AA1	GSM4909297	Human	Breast	IDC	3.82e-08	9.75e-02	0.1517
3320	HSP90AA1	GSM4909302	Human	Breast	IDC	1.16e-08	-4.68e-01	0.1545
3320	HSP90AA1	GSM4909304	Human	Breast	IDC	1.91e-16	2.75e-01	0.1636
3320	HSP90AA1	GSM4909311	Human	Breast	IDC	2.88e-51	-9.80e-01	0.1534
3320	HSP90AA1	GSM4909312	Human	Breast	IDC	1.96e-22	-6.88e-01	0.1552
3320	HSP90AA1	GSM4909313	Human	Breast	IDC	1.72e-13	-5.86e-01	0.0391
3320	HSP90AA1	GSM4909315	Human	Breast	IDC	1.29e-04	-9.93e-02	0.21
3320	HSP90AA1	GSM4909317	Human	Breast	IDC	9.89e-41	5.55e-01	0.1355
3320	HSP90AA1	GSM4909319	Human	Breast	IDC	1.48e-39	-4.60e-01	0.1563
3320	HSP90AA1	GSM4909321	Human	Breast	IDC	8.00e-04	1.13e-01	0.1559
3320	HSP90AA1	brca1	Human	Breast	Precancer	6.96e-08	1.70e-01	-0.0338
3320	HSP90AA1	brca3	Human	Breast	Precancer	2.41e-04	-7.36e-02	-0.0263
3320	HSP90AA1	brca10	Human	Breast	Precancer	1.90e-07	-4.34e-01	-0.0029
3320	HSP90AA1	M2	Human	Breast	IDC	7.82e-07	3.95e-01	0.21

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:00616843	Stomach	CAG	chaperone-mediated autophagy	5/552	16/18723	7.30e-05	2.01e-03	5
GO:00068093	Stomach	CAG	nitric oxide biosynthetic process	10/552	76/18723	7.60e-05	2.07e-03	10
GO:00454283	Stomach	CAG	regulation of nitric oxide biosynthetic process	9/552	62/18723	7.95e-05	2.13e-03	9
GO:00801643	Stomach	CAG	regulation of nitric oxide metabolic process	9/552	64/18723	1.02e-04	2.63e-03	9
GO:00462093	Stomach	CAG	nitric oxide metabolic process	10/552	81/18723	1.31e-04	3.22e-03	10
GO:20010573	Stomach	CAG	reactive nitrogen species metabolic process	10/552	82/18723	1.46e-04	3.38e-03	10
GO:000683931	Stomach	CAG	mitochondrial transport	19/552	254/18723	2.03e-04	4.32e-03	19
GO:005125831	Stomach	CAG	protein polymerization	21/552	297/18723	2.09e-04	4.32e-03	21
GO:007265531	Stomach	CAG	establishment of protein localization to mitochondrion	12/552	120/18723	2.24e-04	4.52e-03	12
GO:007058531	Stomach	CAG	protein localization to mitochondrion	12/552	125/18723	3.27e-04	6.06e-03	12
GO:005197231	Stomach	CAG	regulation of telomerase activity	7/552	47/18723	4.21e-04	7.49e-03	7
GO:19029473	Stomach	CAG	regulation of tau-protein kinase activity	4/552	13/18723	4.32e-04	7.54e-03	4
GO:004573231	Stomach	CAG	positive regulation of protein catabolic process	17/552	231/18723	5.21e-04	8.77e-03	17
GO:000940931	Stomach	CAG	response to cold	7/552	49/18723	5.47e-04	9.07e-03	7
GO:003227131	Stomach	CAG	regulation of protein polymerization	17/552	233/18723	5.74e-04	9.49e-03	17
GO:001083321	Stomach	CAG	telomere maintenance via telomere lengthening	9/552	81/18723	6.24e-04	1.02e-02	9
GO:190336431	Stomach	CAG	positive regulation of cellular protein catabolic process	13/552	155/18723	6.94e-04	1.10e-02	13
GO:00018193	Stomach	CAG	positive regulation of cytokine production	27/552	467/18723	7.24e-04	1.13e-02	27
GO:000662631	Stomach	CAG	protein targeting to mitochondrion	10/552	100/18723	7.35e-04	1.13e-02	10
GO:003227331	Stomach	CAG	positive regulation of protein polymerization	12/552	138/18723	8.02e-04	1.21e-02	12

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513218	Breast	Precancer	Salmonella infection	49/684	249/8465	2.92e-09	6.15e-08	4.71e-08	49
hsa0414118	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0491518	Breast	Precancer	Estrogen signaling pathway	28/684	138/8465	4.10e-06	5.39e-05	4.13e-05	28
hsa0541718	Breast	Precancer	Lipid and atherosclerosis	37/684	215/8465	7.64e-06	9.29e-05	7.12e-05	37
hsa0513219	Breast	Precancer	Salmonella infection	49/684	249/8465	2.92e-09	6.15e-08	4.71e-08	49
hsa0414119	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0491519	Breast	Precancer	Estrogen signaling pathway	28/684	138/8465	4.10e-06	5.39e-05	4.13e-05	28
hsa0541719	Breast	Precancer	Lipid and atherosclerosis	37/684	215/8465	7.64e-06	9.29e-05	7.12e-05	37
hsa0513224	Breast	IDC	Salmonella infection	55/867	249/8465	2.07e-08	4.49e-07	3.36e-07	55
hsa0491523	Breast	IDC	Estrogen signaling pathway	35/867	138/8465	2.55e-07	5.18e-06	3.88e-06	35
hsa0461223	Breast	IDC	Antigen processing and presentation	24/867	78/8465	4.61e-07	8.33e-06	6.23e-06	24
hsa0541824	Breast	IDC	Fluid shear stress and atherosclerosis	34/867	139/8465	9.41e-07	1.61e-05	1.20e-05	34
hsa0414124	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0541724	Breast	IDC	Lipid and atherosclerosis	35/867	215/8465	3.67e-03	2.29e-02	1.71e-02	35
hsa0465721	Breast	IDC	IL-17 signaling pathway	18/867	94/8465	6.39e-03	3.30e-02	2.47e-02	18
hsa0513234	Breast	IDC	Salmonella infection	55/867	249/8465	2.07e-08	4.49e-07	3.36e-07	55
hsa0491533	Breast	IDC	Estrogen signaling pathway	35/867	138/8465	2.55e-07	5.18e-06	3.88e-06	35
hsa0461233	Breast	IDC	Antigen processing and presentation	24/867	78/8465	4.61e-07	8.33e-06	6.23e-06	24
hsa0541834	Breast	IDC	Fluid shear stress and atherosclerosis	34/867	139/8465	9.41e-07	1.61e-05	1.20e-05	34
hsa0414134	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36

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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

HSP90AA1

SNV

Missense_Mutation

c.1194N>C

p.Lys398Asn

p.K398N

P07900

protein_coding

deleterious_low_confidence(0)

benign(0.009)

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

HSP90AA1

SNV

Missense_Mutation

c.433N>G

p.Gln145Glu

p.Q145E

P07900

protein_coding

deleterious_low_confidence(0.01)

benign(0.129)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HSP90AA1

SNV

Missense_Mutation

novel

c.199N>A

p.Leu67Ile

p.L67I

P07900

protein_coding

deleterious_low_confidence(0)

benign(0.006)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HSP90AA1

SNV

Missense_Mutation

c.2323N>A

p.Asp775Asn

p.D775N

P07900

protein_coding

tolerated_low_confidence(0.06)

possibly_damaging(0.619)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

HSP90AA1

SNV

Missense_Mutation

c.1863G>C

p.Lys621Asn

p.K621N

P07900

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(0.975)

TCGA-C8-A1HM-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

doxorubicin

HSP90AA1

SNV

Missense_Mutation

novel

c.1379G>C

p.Arg460Thr

p.R460T

P07900

protein_coding

tolerated_low_confidence(0.05)

possibly_damaging(0.709)

TCGA-C5-A7UI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HSP90AA1

SNV

Missense_Mutation

c.418N>A

p.Glu140Lys

p.E140K

P07900

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.977)

TCGA-EK-A2RA-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

HSP90AA1

SNV

Missense_Mutation

c.821N>T

p.Thr274Ile

p.T274I

P07900

protein_coding

tolerated_low_confidence(0.06)

probably_damaging(0.997)

TCGA-EX-A69M-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

HSP90AA1

SNV

Missense_Mutation

c.2288N>G

p.Ser763Cys

p.S763C

P07900

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.973)

TCGA-IR-A3LA-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HSP90AA1

SNV

Missense_Mutation

novel

c.760N>C

p.Gly254Arg

p.G254R

P07900

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(1)

TCGA-JX-A5QV-01

Cervix

cervical & endocervical cancer

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
3320	HSP90AA1	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR		SJ000018300	CHEMBL590927
3320	HSP90AA1	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR		TCMDC-123828	CHEMBL588804
3320	HSP90AA1	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR		GNF-PF-3641	CHEMBL599098
3320	HSP90AA1	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR		BIFONAZOLE	BIFONAZOLE
3320	HSP90AA1	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR		KEPONE	KEPONE
3320	HSP90AA1	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR		SJ000032151	CHEMBL592600
3320	HSP90AA1	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR		DNDI1417086	CHEMBL1224755
3320	HSP90AA1	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR		RETASPIMYCIN	RETASPIMYCIN
3320	HSP90AA1	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR		SCLEROTIORIN	SCLEROTIORIN
3320	HSP90AA1	CLINICALLY ACTIONABLE, DRUGGABLE GENOME, TRANSCRIPTION FACTOR		TRICLABENDAZOLE	TRICLABENDAZOLE

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