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: HSPBP1

Gene summary for HSPBP1

Gene summary.

Gene information	Species	Human
	Gene symbol	HSPBP1
	Gene ID	23640
	Gene name	HSPA (Hsp70) binding protein 1
	Gene Alias	FES1
	Cytomap	19q13.42
	Gene Type	protein-coding
	GO ID	GO:0006457
	UniProtAcc	Q9NZL4

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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
23640	HSPBP1	HTA11_3410_2000001011	Human	Colorectum	AD	6.81e-04	2.01e-01	0.0155
23640	HSPBP1	HTA11_2487_2000001011	Human	Colorectum	SER	1.42e-11	4.58e-01	-0.1808
23640	HSPBP1	HTA11_1938_2000001011	Human	Colorectum	AD	2.14e-16	5.75e-01	-0.0811
23640	HSPBP1	HTA11_78_2000001011	Human	Colorectum	AD	1.93e-02	2.49e-01	-0.1088
23640	HSPBP1	HTA11_347_2000001011	Human	Colorectum	AD	2.96e-14	4.22e-01	-0.1954
23640	HSPBP1	HTA11_411_2000001011	Human	Colorectum	SER	3.57e-03	5.18e-01	-0.2602
23640	HSPBP1	HTA11_3361_2000001011	Human	Colorectum	AD	6.17e-08	4.46e-01	-0.1207
23640	HSPBP1	HTA11_83_2000001011	Human	Colorectum	SER	5.37e-08	4.81e-01	-0.1526
23640	HSPBP1	HTA11_696_2000001011	Human	Colorectum	AD	5.32e-15	4.25e-01	-0.1464
23640	HSPBP1	HTA11_866_2000001011	Human	Colorectum	AD	2.24e-03	2.47e-01	-0.1001
23640	HSPBP1	HTA11_1391_2000001011	Human	Colorectum	AD	2.85e-13	4.95e-01	-0.059
23640	HSPBP1	HTA11_2992_2000001011	Human	Colorectum	SER	1.64e-04	4.03e-01	-0.1706
23640	HSPBP1	HTA11_5216_2000001011	Human	Colorectum	SER	1.84e-02	3.58e-01	-0.1462
23640	HSPBP1	HTA11_546_2000001011	Human	Colorectum	AD	1.41e-03	3.32e-01	-0.0842
23640	HSPBP1	HTA11_866_3004761011	Human	Colorectum	AD	6.00e-08	2.93e-01	0.096
23640	HSPBP1	HTA11_8622_2000001021	Human	Colorectum	SER	2.05e-03	3.20e-01	0.0528
23640	HSPBP1	HTA11_10623_2000001011	Human	Colorectum	AD	2.27e-05	4.03e-01	-0.0177
23640	HSPBP1	HTA11_6801_2000001011	Human	Colorectum	SER	3.50e-02	3.32e-01	0.0171
23640	HSPBP1	HTA11_10711_2000001011	Human	Colorectum	AD	4.75e-02	2.88e-01	0.0338
23640	HSPBP1	HTA11_7696_3000711011	Human	Colorectum	AD	7.74e-31	7.66e-01	0.0674

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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
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:0042176	Colorectum	AD	regulation of protein catabolic process	160/3918	391/18723	1.06e-19	7.34e-17	160
GO:0009896	Colorectum	AD	positive regulation of catabolic process	180/3918	492/18723	4.33e-16	1.94e-13	180
GO:1903362	Colorectum	AD	regulation of cellular protein catabolic process	109/3918	255/18723	2.14e-15	6.08e-13	109
GO:0010498	Colorectum	AD	proteasomal protein catabolic process	174/3918	490/18723	3.18e-14	7.66e-12	174
GO:0031331	Colorectum	AD	positive regulation of cellular catabolic process	156/3918	427/18723	4.68e-14	1.05e-11	156
GO:1903050	Colorectum	AD	regulation of proteolysis involved in cellular protein catabolic process	92/3918	221/18723	2.04e-12	3.19e-10	92
GO:0045732	Colorectum	AD	positive regulation of protein catabolic process	92/3918	231/18723	3.85e-11	4.47e-09	92
GO:0043161	Colorectum	AD	proteasome-mediated ubiquitin-dependent protein catabolic process	141/3918	412/18723	1.77e-10	1.68e-08	141
GO:0045862	Colorectum	AD	positive regulation of proteolysis	129/3918	372/18723	4.04e-10	3.46e-08	129
GO:0061136	Colorectum	AD	regulation of proteasomal protein catabolic process	75/3918	187/18723	1.65e-09	1.20e-07	75
GO:2000058	Colorectum	AD	regulation of ubiquitin-dependent protein catabolic process	68/3918	164/18723	1.82e-09	1.31e-07	68
GO:1903364	Colorectum	AD	positive regulation of cellular protein catabolic process	62/3918	155/18723	4.66e-08	2.51e-06	62
GO:1903320	Colorectum	AD	regulation of protein modification by small protein conjugation or removal	86/3918	242/18723	9.43e-08	4.65e-06	86
GO:0032434	Colorectum	AD	regulation of proteasomal ubiquitin-dependent protein catabolic process	54/3918	134/18723	2.51e-07	1.02e-05	54
GO:1903052	Colorectum	AD	positive regulation of proteolysis involved in cellular protein catabolic process	53/3918	133/18723	4.93e-07	1.85e-05	53
GO:2000060	Colorectum	AD	positive regulation of ubiquitin-dependent protein catabolic process	44/3918	107/18723	1.65e-06	5.03e-05	44
GO:0006457	Colorectum	AD	protein folding	73/3918	212/18723	3.24e-06	9.10e-05	73
GO:0031396	Colorectum	AD	regulation of protein ubiquitination	72/3918	210/18723	4.50e-06	1.21e-04	72
GO:1901800	Colorectum	AD	positive regulation of proteasomal protein catabolic process	44/3918	114/18723	1.18e-05	2.62e-04	44
GO:0032436	Colorectum	AD	positive regulation of proteasomal ubiquitin-dependent protein catabolic process	36/3918	90/18723	2.89e-05	5.37e-04	36

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04141	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa041411	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa041412	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
hsa041413	Colorectum	SER	Protein processing in endoplasmic reticulum	60/1580	174/8465	4.20e-07	7.33e-06	5.32e-06	60
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
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
hsa0414114	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0414115	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0414122	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0414132	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0414130	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa04141113	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa04141210	Oral cavity	LP	Protein processing in endoplasmic reticulum	113/2418	174/8465	8.74e-24	5.82e-22	3.76e-22	113
hsa0414138	Oral cavity	LP	Protein processing in endoplasmic reticulum	113/2418	174/8465	8.74e-24	5.82e-22	3.76e-22	113

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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

HSPBP1

SNV

Missense_Mutation

rs764285622

c.107C>T

p.Ser36Leu

p.S36L

Q9NZL4

protein_coding

tolerated(0.08)

benign(0.206)

TCGA-C5-A2LZ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Unknown

HSPBP1

SNV

Missense_Mutation

novel

c.271N>C

p.Glu91Gln

p.E91Q

Q9NZL4

protein_coding

tolerated(0.09)

benign(0.124)

TCGA-R2-A69V-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HSPBP1

deletion

Frame_Shift_Del

novel

c.37delN

p.Leu13TrpfsTer55

p.L13Wfs*55

Q9NZL4

protein_coding

TCGA-MA-AA42-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

HSPBP1

SNV

Missense_Mutation

rs141743392

c.512N>T

p.Thr171Met

p.T171M

Q9NZL4

protein_coding

deleterious(0.01)

probably_damaging(0.976)

TCGA-WS-AB45-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

HSPBP1

SNV

Missense_Mutation

c.215N>A

p.Arg72His

p.R72H

Q9NZL4

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-EI-6882-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

HSPBP1

SNV

Missense_Mutation

rs755814307

c.1063G>A

p.Asp355Asn

p.D355N

Q9NZL4

protein_coding

tolerated(0.36)

possibly_damaging(0.736)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

HSPBP1

SNV

Missense_Mutation

c.139G>T

p.Gly47Cys

p.G47C

Q9NZL4

protein_coding

deleterious(0)

probably_damaging(0.976)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

HSPBP1

SNV

Missense_Mutation

novel

c.53C>T

p.Ala18Val

p.A18V

Q9NZL4

protein_coding

tolerated_low_confidence(0.12)

benign(0.375)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

HSPBP1

SNV

Missense_Mutation

novel

c.874N>T

p.Val292Leu

p.V292L

Q9NZL4

protein_coding

tolerated(0.15)

benign(0.01)

TCGA-AP-A1E0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

HSPBP1

SNV

Missense_Mutation

c.688G>A

p.Asp230Asn

p.D230N

Q9NZL4

protein_coding

tolerated(0.09)

possibly_damaging(0.644)

TCGA-B5-A11U-01

Endometrium

uterine corpus endometrioid carcinoma

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

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