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: HIP1

Gene summary for HIP1

Gene summary.

Gene information	Species	Human
	Gene symbol	HIP1
	Gene ID	3092
	Gene name	huntingtin interacting protein 1
	Gene Alias	HIP-I
	Cytomap	7q11.23
	Gene Type	protein-coding
	GO ID	GO:0006508
	UniProtAcc	B4DK46

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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
3092	HIP1	CCI_2	Human	Cervix	CC	7.82e-04	5.67e-01	0.5249
3092	HIP1	CCI_3	Human	Cervix	CC	3.04e-07	6.98e-01	0.516
3092	HIP1	HTA11_347_2000001011	Human	Colorectum	AD	1.12e-03	3.91e-01	-0.1954
3092	HIP1	HTA11_546_2000001011	Human	Colorectum	AD	1.28e-02	5.12e-01	-0.0842
3092	HIP1	HTA11_99999974143_84620	Human	Colorectum	MSS	4.20e-02	4.44e-01	0.3005
3092	HIP1	A001-C-119	Human	Colorectum	FAP	2.14e-04	5.15e-01	-0.1557
3092	HIP1	A002-C-116	Human	Colorectum	FAP	5.09e-05	-1.78e-01	-0.0452
3092	HIP1	AEH-subject1	Human	Endometrium	AEH	4.17e-15	4.55e-01	-0.3059
3092	HIP1	AEH-subject2	Human	Endometrium	AEH	3.72e-05	3.16e-01	-0.2525
3092	HIP1	AEH-subject3	Human	Endometrium	AEH	2.06e-05	2.39e-01	-0.2576
3092	HIP1	AEH-subject4	Human	Endometrium	AEH	2.10e-03	3.24e-01	-0.2657
3092	HIP1	AEH-subject5	Human	Endometrium	AEH	5.00e-03	2.89e-01	-0.2953
3092	HIP1	EEC-subject1	Human	Endometrium	EEC	4.51e-12	4.09e-01	-0.2682
3092	HIP1	EEC-subject2	Human	Endometrium	EEC	1.82e-07	3.15e-01	-0.2607
3092	HIP1	EEC-subject3	Human	Endometrium	EEC	1.82e-08	2.30e-01	-0.2525
3092	HIP1	EEC-subject4	Human	Endometrium	EEC	8.51e-06	2.52e-01	-0.2571
3092	HIP1	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	1.38e-05	7.39e-02	-0.1869
3092	HIP1	GSM6177620_NYU_UCEC1_lib2_lib2	Human	Endometrium	EEC	4.52e-06	-5.06e-03	-0.1875
3092	HIP1	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	8.08e-07	-2.47e-02	-0.1883
3092	HIP1	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	2.58e-07	1.41e-02	-0.1934

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:00108227	Oral cavity	OSCC	positive regulation of mitochondrion organization	53/7305	74/18723	1.26e-08	2.55e-07	53
GO:000701520	Oral cavity	OSCC	actin filament organization	230/7305	442/18723	1.37e-08	2.77e-07	230
GO:001095019	Oral cavity	OSCC	positive regulation of endopeptidase activity	107/7305	179/18723	1.38e-08	2.78e-07	107
GO:003297020	Oral cavity	OSCC	regulation of actin filament-based process	209/7305	397/18723	1.89e-08	3.72e-07	209
GO:003010016	Oral cavity	OSCC	regulation of endocytosis	121/7305	211/18723	4.74e-08	8.80e-07	121
GO:003253519	Oral cavity	OSCC	regulation of cellular component size	201/7305	383/18723	4.80e-08	8.88e-07	201
GO:00905598	Oral cavity	OSCC	regulation of membrane permeability	54/7305	78/18723	6.05e-08	1.09e-06	54
GO:003295620	Oral cavity	OSCC	regulation of actin cytoskeleton organization	189/7305	358/18723	6.81e-08	1.21e-06	189
GO:003812715	Oral cavity	OSCC	ERBB signaling pathway	76/7305	121/18723	9.59e-08	1.66e-06	76
GO:00469028	Oral cavity	OSCC	regulation of mitochondrial membrane permeability	45/7305	63/18723	1.80e-07	2.92e-06	45
GO:00315034	Oral cavity	OSCC	protein-containing complex localization	123/7305	220/18723	2.54e-07	4.00e-06	123
GO:011005320	Oral cavity	OSCC	regulation of actin filament organization	150/7305	278/18723	2.68e-07	4.15e-06	150
GO:200105618	Oral cavity	OSCC	positive regulation of cysteine-type endopeptidase activity	88/7305	148/18723	3.59e-07	5.40e-06	88
GO:004328018	Oral cavity	OSCC	positive regulation of cysteine-type endopeptidase activity involved in apoptotic process	78/7305	129/18723	6.35e-07	9.03e-06	78
GO:000717315	Oral cavity	OSCC	epidermal growth factor receptor signaling pathway	67/7305	108/18723	1.04e-06	1.40e-05	67
GO:003083817	Oral cavity	OSCC	positive regulation of actin filament polymerization	62/7305	99/18723	1.64e-06	2.14e-05	62
GO:000806417	Oral cavity	OSCC	regulation of actin polymerization or depolymerization	104/7305	188/18723	3.99e-06	4.66e-05	104
GO:003209210	Oral cavity	OSCC	positive regulation of protein binding	54/7305	85/18723	4.05e-06	4.71e-05	54
GO:003083216	Oral cavity	OSCC	regulation of actin filament length	104/7305	189/18723	5.48e-06	6.14e-05	104
GO:003083318	Oral cavity	OSCC	regulation of actin filament polymerization	96/7305	172/18723	5.56e-06	6.20e-05	96

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501618	Cervix	CC	Huntington disease	94/1267	306/8465	8.49e-13	3.06e-11	1.81e-11	94
hsa0502218	Cervix	CC	Pathways of neurodegeneration - multiple diseases	128/1267	476/8465	2.87e-12	9.29e-11	5.50e-11	128
hsa0501619	Cervix	CC	Huntington disease	94/1267	306/8465	8.49e-13	3.06e-11	1.81e-11	94
hsa0502219	Cervix	CC	Pathways of neurodegeneration - multiple diseases	128/1267	476/8465	2.87e-12	9.29e-11	5.50e-11	128
hsa05016	Colorectum	AD	Huntington disease	147/2092	306/8465	1.93e-19	9.26e-18	5.91e-18	147
hsa05022	Colorectum	AD	Pathways of neurodegeneration - multiple diseases	201/2092	476/8465	4.54e-18	1.27e-16	8.09e-17	201
hsa050161	Colorectum	AD	Huntington disease	147/2092	306/8465	1.93e-19	9.26e-18	5.91e-18	147
hsa050221	Colorectum	AD	Pathways of neurodegeneration - multiple diseases	201/2092	476/8465	4.54e-18	1.27e-16	8.09e-17	201
hsa050164	Colorectum	MSS	Huntington disease	141/1875	306/8465	2.90e-21	1.62e-19	9.92e-20	141
hsa050224	Colorectum	MSS	Pathways of neurodegeneration - multiple diseases	192/1875	476/8465	2.79e-20	1.04e-18	6.36e-19	192
hsa050165	Colorectum	MSS	Huntington disease	141/1875	306/8465	2.90e-21	1.62e-19	9.92e-20	141
hsa050225	Colorectum	MSS	Pathways of neurodegeneration - multiple diseases	192/1875	476/8465	2.79e-20	1.04e-18	6.36e-19	192
hsa050228	Colorectum	FAP	Pathways of neurodegeneration - multiple diseases	117/1404	476/8465	2.81e-06	4.47e-05	2.72e-05	117
hsa050168	Colorectum	FAP	Huntington disease	73/1404	306/8465	5.54e-04	3.93e-03	2.39e-03	73
hsa050229	Colorectum	FAP	Pathways of neurodegeneration - multiple diseases	117/1404	476/8465	2.81e-06	4.47e-05	2.72e-05	117
hsa050169	Colorectum	FAP	Huntington disease	73/1404	306/8465	5.54e-04	3.93e-03	2.39e-03	73
hsa0501620	Endometrium	AEH	Huntington disease	118/1197	306/8465	3.00e-27	2.44e-25	1.78e-25	118
hsa0502220	Endometrium	AEH	Pathways of neurodegeneration - multiple diseases	137/1197	476/8465	9.27e-18	2.32e-16	1.70e-16	137
hsa05016110	Endometrium	AEH	Huntington disease	118/1197	306/8465	3.00e-27	2.44e-25	1.78e-25	118
hsa05022110	Endometrium	AEH	Pathways of neurodegeneration - multiple diseases	137/1197	476/8465	9.27e-18	2.32e-16	1.70e-16	137

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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

HIP1

SNV

Missense_Mutation

novel

c.341N>A

p.Ser114Tyr

p.S114Y

O00291

protein_coding

tolerated(0.28)

possibly_damaging(0.883)

TCGA-A2-A0EV-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HIP1

SNV

Missense_Mutation

rs782471782

c.1729C>T

p.Arg577Trp

p.R577W

O00291

protein_coding

deleterious(0)

benign(0.309)

TCGA-A8-A09Z-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HIP1

SNV

Missense_Mutation

c.3067N>C

p.Glu1023Gln

p.E1023Q

O00291

protein_coding

tolerated(0.09)

benign(0.006)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HIP1

SNV

Missense_Mutation

c.2572C>G

p.Pro858Ala

p.P858A

O00291

protein_coding

tolerated(0.68)

benign(0.012)

TCGA-B6-A0I8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HIP1

SNV

Missense_Mutation

c.757N>A

p.Asp253Asn

p.D253N

O00291

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-B6-A1KF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HIP1

SNV

Missense_Mutation

rs587756668

c.2482N>C

p.Thr828Pro

p.T828P

O00291

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-D8-A1X7-01

Breast

breast invasive carcinoma

Female

<65

I/II

ChemotherapyHormone Therapy

doxorubicine+cyclophosphamide+tamoxifen

HIP1

SNV

Missense_Mutation

novel

c.2213N>A

p.Ser738Tyr

p.S738Y

O00291

protein_coding

deleterious(0.04)

benign(0.003)

TCGA-E9-A1RB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

methotrexate

HIP1

insertion

Frame_Shift_Ins

novel

c.338_339insTCTGTCTGCACCTATAAAATGTTGGCAACTATGTAGTC

p.Ser114LeufsTer15

p.S114Lfs*15

O00291

protein_coding

TCGA-A2-A0EV-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HIP1

SNV

Missense_Mutation

rs782794159

c.228C>G

p.Phe76Leu

p.F76L

O00291

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-IR-A3LL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HIP1

SNV

Missense_Mutation

c.2855N>T

p.Ser952Leu

p.S952L

O00291

protein_coding

deleterious(0)

probably_damaging(0.962)

TCGA-Q1-A73P-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

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