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: HSPA6

Gene summary for HSPA6

Gene summary.

Gene information	Species	Human
	Gene symbol	HSPA6
	Gene ID	3310
	Gene name	heat shock protein family A (Hsp70) member 6
	Gene Alias	HSP70B'
	Cytomap	1q23.3
	Gene Type	protein-coding
	GO ID	GO:0006457
	UniProtAcc	B3KSM6

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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
3310	HSPA6	GSM4909277	Human	Breast	Precancer	3.18e-10	1.67e+00	0.0177
3310	HSPA6	GSM4909282	Human	Breast	IDC	1.27e-03	-4.01e-01	-0.0288
3310	HSPA6	GSM4909285	Human	Breast	IDC	3.78e-06	-4.13e-01	0.21
3310	HSPA6	GSM4909286	Human	Breast	IDC	8.25e-07	-4.23e-01	0.1081
3310	HSPA6	GSM4909293	Human	Breast	IDC	1.68e-02	-4.13e-01	0.1581
3310	HSPA6	GSM4909298	Human	Breast	IDC	2.10e-02	-3.15e-01	0.1551
3310	HSPA6	GSM4909300	Human	Breast	IDC	3.30e-02	-4.24e-01	0.0334
3310	HSPA6	GSM4909304	Human	Breast	IDC	5.41e-08	-2.98e-02	0.1636
3310	HSPA6	GSM4909317	Human	Breast	IDC	5.23e-15	6.62e-01	0.1355
3310	HSPA6	brca1	Human	Breast	Precancer	3.78e-06	-4.19e-01	-0.0338
3310	HSPA6	brca2	Human	Breast	Precancer	5.18e-04	-4.14e-01	-0.024
3310	HSPA6	brca3	Human	Breast	Precancer	3.77e-05	-4.17e-01	-0.0263
3310	HSPA6	DCIS2	Human	Breast	DCIS	8.61e-03	-3.87e-01	0.0085
3310	HSPA6	sample1	Human	Cervix	CC	2.32e-19	9.97e-01	0.0959
3310	HSPA6	L1	Human	Cervix	CC	5.89e-09	6.32e-01	0.0802
3310	HSPA6	T1	Human	Cervix	CC	6.12e-34	1.04e+00	0.0918
3310	HSPA6	LZE4T	Human	Esophagus	ESCC	3.14e-23	3.48e+00	0.0811
3310	HSPA6	LZE20T	Human	Esophagus	ESCC	3.65e-10	2.73e+00	0.0662
3310	HSPA6	LZE22T	Human	Esophagus	ESCC	5.32e-04	2.98e+00	0.068
3310	HSPA6	LZE24D1	Human	Esophagus	HGIN	5.28e-14	8.83e-01	0.054

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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
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:00064578	Breast	Precancer	protein folding	43/1080	212/18723	3.48e-13	7.45e-11	43
GO:00064588	Breast	Precancer	'de novo' protein folding	16/1080	43/18723	8.14e-10	6.92e-08	16
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: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
GO:00092667	Breast	Precancer	response to temperature stimulus	27/1080	178/18723	3.85e-06	1.21e-04	27
GO:00346059	Breast	Precancer	cellular response to heat	15/1080	69/18723	7.08e-06	1.95e-04	15
GO:00094088	Breast	Precancer	response to heat	18/1080	110/18723	5.57e-05	1.15e-03	18
GO:000645713	Breast	IDC	protein folding	47/1434	212/18723	2.31e-11	3.86e-09	47
GO:006107713	Breast	IDC	chaperone-mediated protein folding	21/1434	67/18723	1.35e-08	9.71e-07	21
GO:000645813	Breast	IDC	'de novo' protein folding	16/1434	43/18723	4.69e-08	3.02e-06	16
GO:000698614	Breast	IDC	response to unfolded protein	30/1434	137/18723	1.24e-07	7.03e-06	30
GO:003596614	Breast	IDC	response to topologically incorrect protein	32/1434	159/18723	3.71e-07	1.85e-05	32
GO:005108413	Breast	IDC	'de novo' posttranslational protein folding	14/1434	39/18723	5.46e-07	2.65e-05	14
GO:000926612	Breast	IDC	response to temperature stimulus	34/1434	178/18723	5.88e-07	2.83e-05	34

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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

HSPA6

SNV

Missense_Mutation

novel

c.1684G>A

p.Asp562Asn

p.D562N

P17066

protein_coding

tolerated_low_confidence(0.13)

possibly_damaging(0.497)

TCGA-B6-A0X1-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HSPA6

SNV

Missense_Mutation

rs777963049

c.1838A>G

p.Tyr613Cys

p.Y613C

P17066

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.981)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HSPA6

SNV

Missense_Mutation

c.800N>A

p.Thr267Lys

p.T267K

P17066

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.999)

TCGA-EW-A1P0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

HSPA6

SNV

Missense_Mutation

rs189929972

c.1729C>T

p.Arg577Trp

p.R577W

P17066

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.511)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HSPA6

SNV

Missense_Mutation

c.871N>A

p.Glu291Lys

p.E291K

P17066

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.647)

TCGA-Q1-A6DW-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HSPA6

SNV

Missense_Mutation

novel

c.1216N>C

p.Glu406Gln

p.E406Q

P17066

protein_coding

deleterious_low_confidence(0)

probably_damaging(1)

TCGA-VS-A9UH-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HSPA6

SNV

Missense_Mutation

novel

c.1770G>C

p.Glu590Asp

p.E590D

P17066

protein_coding

tolerated_low_confidence(0.21)

benign(0.019)

TCGA-VS-AA62-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HSPA6

SNV

Missense_Mutation

c.264C>A

p.Asp88Glu

p.D88E

P17066

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.739)

TCGA-A6-6650-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

HSPA6

SNV

Missense_Mutation

c.430N>A

p.Ala144Thr

p.A144T

P17066

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.93)

TCGA-AA-3492-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

HSPA6

SNV

Missense_Mutation

rs773522375

c.1394N>A

p.Gly465Asp

p.G465D

P17066

protein_coding

deleterious_low_confidence(0.03)

probably_damaging(0.985)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

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

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