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: HSPH1

Gene summary for HSPH1

Gene summary.

Gene information	Species	Human
	Gene symbol	HSPH1
	Gene ID	10808
	Gene name	heat shock protein family H (Hsp110) member 1
	Gene Alias	HSP105
	Cytomap	13q12.3
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	A0A024RDQ0

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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
10808	HSPH1	GSM4909282	Human	Breast	IDC	1.66e-08	-5.00e-01	-0.0288
10808	HSPH1	GSM4909285	Human	Breast	IDC	1.02e-03	-2.82e-01	0.21
10808	HSPH1	GSM4909286	Human	Breast	IDC	6.13e-13	-5.42e-01	0.1081
10808	HSPH1	GSM4909290	Human	Breast	IDC	7.79e-03	-3.66e-01	0.2096
10808	HSPH1	GSM4909293	Human	Breast	IDC	7.59e-07	2.20e-01	0.1581
10808	HSPH1	GSM4909294	Human	Breast	IDC	4.23e-03	-3.99e-01	0.2022
10808	HSPH1	GSM4909297	Human	Breast	IDC	2.62e-05	2.28e-01	0.1517
10808	HSPH1	GSM4909298	Human	Breast	IDC	1.14e-02	-3.34e-01	0.1551
10808	HSPH1	GSM4909307	Human	Breast	IDC	4.78e-13	-5.46e-01	0.1569
10808	HSPH1	GSM4909308	Human	Breast	IDC	7.30e-03	-3.06e-01	0.158
10808	HSPH1	GSM4909309	Human	Breast	IDC	5.99e-09	-4.58e-01	0.0483
10808	HSPH1	GSM4909311	Human	Breast	IDC	1.39e-28	-6.13e-01	0.1534
10808	HSPH1	GSM4909312	Human	Breast	IDC	4.87e-17	-5.30e-01	0.1552
10808	HSPH1	GSM4909313	Human	Breast	IDC	2.03e-11	-4.81e-01	0.0391
10808	HSPH1	GSM4909317	Human	Breast	IDC	1.27e-06	5.33e-01	0.1355
10808	HSPH1	GSM4909319	Human	Breast	IDC	3.13e-23	-5.46e-01	0.1563
10808	HSPH1	GSM4909320	Human	Breast	IDC	3.98e-04	-4.74e-01	0.1575
10808	HSPH1	GSM4909321	Human	Breast	IDC	1.83e-10	-4.61e-01	0.1559
10808	HSPH1	brca1	Human	Breast	Precancer	2.48e-05	-4.26e-01	-0.0338
10808	HSPH1	brca2	Human	Breast	Precancer	1.52e-03	-2.59e-01	-0.024

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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: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:00457859	Breast	Precancer	positive regulation of cell adhesion	52/1080	437/18723	5.74e-07	2.49e-05	52
GO:00421107	Breast	Precancer	T cell activation	52/1080	487/18723	1.37e-05	3.42e-04	52
GO:00508707	Breast	Precancer	positive regulation of T cell activation	29/1080	216/18723	1.94e-05	4.58e-04	29
GO:19030396	Breast	Precancer	positive regulation of leukocyte cell-cell adhesion	30/1080	239/18723	5.13e-05	1.07e-03	30
GO:00508637	Breast	Precancer	regulation of T cell activation	37/1080	329/18723	8.04e-05	1.56e-03	37
GO:00224098	Breast	Precancer	positive regulation of cell-cell adhesion	33/1080	284/18723	1.03e-04	1.89e-03	33
GO:00071597	Breast	Precancer	leukocyte cell-cell adhesion	40/1080	371/18723	1.07e-04	1.94e-03	40
GO:00224079	Breast	Precancer	regulation of cell-cell adhesion	45/1080	448/18723	2.12e-04	3.30e-03	45
GO:19030377	Breast	Precancer	regulation of leukocyte cell-cell adhesion	36/1080	336/18723	2.61e-04	3.84e-03	36
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

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414118	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0414119	Breast	Precancer	Protein processing in endoplasmic reticulum	33/684	174/8465	2.78e-06	3.83e-05	2.94e-05	33
hsa0414124	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0414134	Breast	IDC	Protein processing in endoplasmic reticulum	36/867	174/8465	2.73e-05	2.86e-04	2.14e-04	36
hsa0414143	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
hsa0414153	Breast	DCIS	Protein processing in endoplasmic reticulum	36/846	174/8465	1.60e-05	1.91e-04	1.41e-04	36
hsa0414120	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa04141110	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa0414144	Cervix	N_HPV	Protein processing in endoplasmic reticulum	21/349	174/8465	8.84e-06	1.09e-04	8.55e-05	21
hsa0414154	Cervix	N_HPV	Protein processing in endoplasmic reticulum	21/349	174/8465	8.84e-06	1.09e-04	8.55e-05	21
hsa041414	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa041415	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa0414126	Endometrium	AEH	Protein processing in endoplasmic reticulum	62/1197	174/8465	5.97e-13	1.39e-11	1.01e-11	62
hsa04141111	Endometrium	AEH	Protein processing in endoplasmic reticulum	62/1197	174/8465	5.97e-13	1.39e-11	1.01e-11	62
hsa0414127	Endometrium	EEC	Protein processing in endoplasmic reticulum	64/1237	174/8465	2.17e-13	5.09e-12	3.80e-12	64
hsa0414136	Endometrium	EEC	Protein processing in endoplasmic reticulum	64/1237	174/8465	2.17e-13	5.09e-12	3.80e-12	64
hsa0414139	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa04141114	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa04141211	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa04141310	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147

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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

HSPH1

SNV

Missense_Mutation

novel

c.1742N>C

p.Asp581Ala

p.D581A

Q92598

protein_coding

tolerated(0.05)

possibly_damaging(0.627)

TCGA-A2-A1G4-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

adriamycin

HSPH1

SNV

Missense_Mutation

novel

c.1077N>A

p.Phe359Leu

p.F359L

Q92598

protein_coding

deleterious(0.05)

possibly_damaging(0.897)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HSPH1

SNV

Missense_Mutation

novel

c.1742A>C

p.Asp581Ala

p.D581A

Q92598

protein_coding

tolerated(0.05)

possibly_damaging(0.627)

TCGA-AO-A1KT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

fluorouracil

HSPH1

SNV

Missense_Mutation

novel

c.1742N>C

p.Asp581Ala

p.D581A

Q92598

protein_coding

tolerated(0.05)

possibly_damaging(0.627)

TCGA-B6-A1KF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HSPH1

SNV

Missense_Mutation

c.1869N>T

p.Met623Ile

p.M623I

Q92598

protein_coding

deleterious(0.02)

probably_damaging(0.968)

TCGA-B6-A1KN-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

HSPH1

SNV

Missense_Mutation

c.1420G>C

p.Asp474His

p.D474H

Q92598

protein_coding

deleterious(0)

probably_damaging(0.973)

TCGA-BH-A0W7-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

HSPH1

SNV

Missense_Mutation

novel

c.1742N>C

p.Asp581Ala

p.D581A

Q92598

protein_coding

tolerated(0.05)

possibly_damaging(0.627)

TCGA-BH-A1F2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

HSPH1

SNV

Missense_Mutation

novel

c.1742A>C

p.Asp581Ala

p.D581A

Q92598

protein_coding

tolerated(0.05)

possibly_damaging(0.627)

TCGA-BH-A1F5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HSPH1

SNV

Missense_Mutation

novel

c.1742A>C

p.Asp581Ala

p.D581A

Q92598

protein_coding

tolerated(0.05)

possibly_damaging(0.627)

TCGA-BH-A1F8-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

HSPH1

SNV

Missense_Mutation

novel

c.1742A>C

p.Asp581Ala

p.D581A

Q92598

protein_coding

tolerated(0.05)

possibly_damaging(0.627)

TCGA-D8-A1JT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

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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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