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: HSPA8

Gene summary for HSPA8

Gene summary.

Gene information	Species	Human
	Gene symbol	HSPA8
	Gene ID	3312
	Gene name	heat shock protein family A (Hsp70) member 8
	Gene Alias	HEL-33
	Cytomap	11q24.1
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	P11142

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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
3312	HSPA8	GSM4909277	Human	Breast	Precancer	7.34e-03	4.84e-01	0.0177
3312	HSPA8	GSM4909285	Human	Breast	IDC	1.60e-04	2.24e-01	0.21
3312	HSPA8	GSM4909286	Human	Breast	IDC	5.42e-07	-3.08e-01	0.1081
3312	HSPA8	GSM4909291	Human	Breast	IDC	3.59e-12	4.66e-01	0.1753
3312	HSPA8	GSM4909294	Human	Breast	IDC	4.86e-12	2.86e-02	0.2022
3312	HSPA8	GSM4909296	Human	Breast	IDC	2.71e-10	-3.27e-01	0.1524
3312	HSPA8	GSM4909297	Human	Breast	IDC	3.52e-22	3.47e-02	0.1517
3312	HSPA8	GSM4909304	Human	Breast	IDC	9.65e-17	4.21e-01	0.1636
3312	HSPA8	GSM4909305	Human	Breast	IDC	1.15e-02	9.26e-02	0.0436
3312	HSPA8	GSM4909307	Human	Breast	IDC	3.60e-02	-3.38e-01	0.1569
3312	HSPA8	GSM4909308	Human	Breast	IDC	9.83e-07	2.06e-01	0.158
3312	HSPA8	GSM4909309	Human	Breast	IDC	6.46e-14	-6.80e-01	0.0483
3312	HSPA8	GSM4909311	Human	Breast	IDC	9.95e-39	-2.26e-01	0.1534
3312	HSPA8	GSM4909312	Human	Breast	IDC	1.44e-29	3.76e-01	0.1552
3312	HSPA8	GSM4909315	Human	Breast	IDC	1.68e-06	-4.15e-01	0.21
3312	HSPA8	GSM4909317	Human	Breast	IDC	4.87e-12	4.12e-01	0.1355
3312	HSPA8	GSM4909319	Human	Breast	IDC	4.12e-54	-6.59e-01	0.1563
3312	HSPA8	GSM4909320	Human	Breast	IDC	9.54e-04	-4.88e-01	0.1575
3312	HSPA8	GSM4909321	Human	Breast	IDC	3.75e-20	2.21e-01	0.1559
3312	HSPA8	brca1	Human	Breast	Precancer	5.26e-10	3.36e-01	-0.0338

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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:00460349	Breast	Precancer	ATP metabolic process	82/1080	277/18723	1.94e-36	5.19e-33	82
GO:00064578	Breast	Precancer	protein folding	43/1080	212/18723	3.48e-13	7.45e-11	43
GO:00083809	Breast	Precancer	RNA splicing	65/1080	434/18723	1.27e-12	2.53e-10	65
GO:00434849	Breast	Precancer	regulation of RNA splicing	34/1080	148/18723	2.66e-12	4.75e-10	34
GO:00003759	Breast	Precancer	RNA splicing, via transesterification reactions	52/1080	324/18723	1.74e-11	2.22e-09	52
GO:00003779	Breast	Precancer	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	51/1080	320/18723	3.55e-11	4.04e-09	51
GO:00003989	Breast	Precancer	mRNA splicing, via spliceosome	51/1080	320/18723	3.55e-11	4.04e-09	51
GO:00160329	Breast	Precancer	viral process	58/1080	415/18723	3.42e-10	3.16e-08	58
GO:00064588	Breast	Precancer	'de novo' protein folding	16/1080	43/18723	8.14e-10	6.92e-08	16
GO:00190589	Breast	Precancer	viral life cycle	47/1080	317/18723	2.42e-09	1.99e-07	47
GO:00069869	Breast	Precancer	response to unfolded protein	28/1080	137/18723	3.81e-09	3.00e-07	28
GO:00610778	Breast	Precancer	chaperone-mediated protein folding	19/1080	67/18723	4.22e-09	3.28e-07	19
GO:00510848	Breast	Precancer	'de novo' posttranslational protein folding	14/1080	39/18723	1.61e-08	1.12e-06	14
GO:00510858	Breast	Precancer	chaperone cofactor-dependent protein refolding	13/1080	34/18723	2.17e-08	1.47e-06	13
GO:00359669	Breast	Precancer	response to topologically incorrect protein	29/1080	159/18723	3.00e-08	1.89e-06	29
GO:00444039	Breast	Precancer	biological process involved in symbiotic interaction	42/1080	290/18723	3.40e-08	2.11e-06	42
GO:00480249	Breast	Precancer	regulation of mRNA splicing, via spliceosome	22/1080	101/18723	5.29e-08	3.18e-06	22
GO:00346209	Breast	Precancer	cellular response to unfolded protein	21/1080	96/18723	9.80e-08	5.46e-06	21
GO:00420268	Breast	Precancer	protein refolding	10/1080	23/18723	2.25e-07	1.13e-05	10
GO:00359679	Breast	Precancer	cellular response to topologically incorrect protein	22/1080	116/18723	6.84e-07	2.80e-05	22

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0502016	Breast	Precancer	Prion disease	95/684	273/8465	1.39e-37	1.46e-35	1.12e-35	95
hsa0513414	Breast	Precancer	Legionellosis	19/684	57/8465	4.62e-08	9.12e-07	6.98e-07	19
hsa030408	Breast	Precancer	Spliceosome	39/684	217/8465	1.44e-06	2.27e-05	1.74e-05	39
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
hsa0461218	Breast	Precancer	Antigen processing and presentation	19/684	78/8465	9.61e-06	1.12e-04	8.62e-05	19
hsa0502017	Breast	Precancer	Prion disease	95/684	273/8465	1.39e-37	1.46e-35	1.12e-35	95
hsa0513415	Breast	Precancer	Legionellosis	19/684	57/8465	4.62e-08	9.12e-07	6.98e-07	19
hsa0304013	Breast	Precancer	Spliceosome	39/684	217/8465	1.44e-06	2.27e-05	1.74e-05	39
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
hsa0461219	Breast	Precancer	Antigen processing and presentation	19/684	78/8465	9.61e-06	1.12e-04	8.62e-05	19
hsa0502023	Breast	IDC	Prion disease	102/867	273/8465	3.70e-34	4.01e-32	3.00e-32	102
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
hsa0513422	Breast	IDC	Legionellosis	19/867	57/8465	1.89e-06	3.07e-05	2.29e-05	19
hsa0414124	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0304023	Breast	IDC	Spliceosome	40/867	217/8465	1.53e-04	1.42e-03	1.06e-03	40

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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

HSPA8

SNV

Missense_Mutation

c.696T>G

p.Asp232Glu

p.D232E

P11142

protein_coding

deleterious_low_confidence(0.02)

benign(0.036)

TCGA-A2-A0EV-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HSPA8

SNV

Missense_Mutation

c.71G>A

p.Gly24Glu

p.G24E

P11142

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(0.957)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HSPA8

SNV

Missense_Mutation

c.1419N>C

p.Gln473His

p.Q473H

P11142

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.957)

TCGA-AO-A0J6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

HSPA8

SNV

Missense_Mutation

novel

c.1392N>G

p.Ile464Met

p.I464M

P11142

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.978)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HSPA8

SNV

Missense_Mutation

novel

c.172N>G

p.Gln58Glu

p.Q58E

P11142

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.958)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

HSPA8

insertion

Frame_Shift_Ins

novel

c.1635_1636insT

p.Ala546CysfsTer9

p.A546Cfs*9

P11142

protein_coding

TCGA-B6-A0I6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HSPA8

insertion

Nonsense_Mutation

novel

c.1633_1634insCCCTCTGGTGGTGCTTCCTCAGGGCCCACCATTGAAGAGGTTG

p.Tyr545SerfsTer12

p.Y545Sfs*12

P11142

protein_coding

TCGA-B6-A0I6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HSPA8

SNV

Missense_Mutation

novel

c.112N>G

p.Thr38Ala

p.T38A

P11142

protein_coding

deleterious_low_confidence(0.01)

benign(0.135)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HSPA8

SNV

Missense_Mutation

c.261N>A

p.Met87Ile

p.M87I

P11142

protein_coding

tolerated_low_confidence(0.16)

benign(0.012)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

HSPA8

SNV

Missense_Mutation

c.1936N>C

p.Asp646His

p.D646H

P11142

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.969)

TCGA-EK-A2R8-01

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
3312	HSPA8	TUMOR SUPPRESSOR		NSC-119910	CHEMBL487046
3312	HSPA8	TUMOR SUPPRESSOR		CISPLATIN	CISPLATIN	15378690
3312	HSPA8	TUMOR SUPPRESSOR		ACETAMINOPHEN	ACETAMINOPHEN	15010265
3312	HSPA8	TUMOR SUPPRESSOR		ANTIBIOTIC	ANTIBIOTIC	14966137
3312	HSPA8	TUMOR SUPPRESSOR	inhibitor	CHEMBL2105726
3312	HSPA8	TUMOR SUPPRESSOR		ELLAGIC ACID	ELLAGIC ACID
3312	HSPA8	TUMOR SUPPRESSOR		NSC-119913	CHEMBL471004
3312	HSPA8	TUMOR SUPPRESSOR		DEXAMETHASONE	DEXAMETHASONE	7542664
3312	HSPA8	TUMOR SUPPRESSOR		HEXACHLOROPHENE	HEXACHLOROPHENE
3312	HSPA8	TUMOR SUPPRESSOR		ADENOSINE TRIPHOSPHATE	ADENOSINE TRIPHOSPHATE

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