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: HIVEP1

Gene summary for HIVEP1

Gene summary.

Gene information	Species	Human
	Gene symbol	HIVEP1
	Gene ID	3096
	Gene name	HIVEP zinc finger 1
	Gene Alias	CIRIP
	Cytomap	6p24.1
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	P15822

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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
3096	HIVEP1	CCI_1	Human	Cervix	CC	7.47e-03	7.06e-01	0.528
3096	HIVEP1	CCI_2	Human	Cervix	CC	1.53e-15	1.74e+00	0.5249
3096	HIVEP1	CCI_3	Human	Cervix	CC	2.01e-08	7.90e-01	0.516
3096	HIVEP1	HTA11_3410_2000001011	Human	Colorectum	AD	1.76e-10	-5.26e-01	0.0155
3096	HIVEP1	HTA11_3361_2000001011	Human	Colorectum	AD	1.17e-04	-5.65e-01	-0.1207
3096	HIVEP1	HTA11_696_2000001011	Human	Colorectum	AD	2.43e-11	-4.77e-01	-0.1464
3096	HIVEP1	HTA11_866_2000001011	Human	Colorectum	AD	4.96e-04	-3.35e-01	-0.1001
3096	HIVEP1	HTA11_866_3004761011	Human	Colorectum	AD	1.63e-07	-4.90e-01	0.096
3096	HIVEP1	HTA11_10711_2000001011	Human	Colorectum	AD	1.07e-05	-5.84e-01	0.0338
3096	HIVEP1	HTA11_7696_3000711011	Human	Colorectum	AD	1.91e-16	-5.13e-01	0.0674
3096	HIVEP1	HTA11_6818_2000001021	Human	Colorectum	AD	3.76e-02	-4.57e-01	0.0588
3096	HIVEP1	HTA11_99999970781_79442	Human	Colorectum	MSS	6.49e-07	-3.46e-01	0.294
3096	HIVEP1	HTA11_99999971662_82457	Human	Colorectum	MSS	2.91e-14	-4.74e-01	0.3859
3096	HIVEP1	HTA11_99999974143_84620	Human	Colorectum	MSS	1.21e-19	-6.10e-01	0.3005
3096	HIVEP1	A015-C-203	Human	Colorectum	FAP	9.98e-28	-2.87e-01	-0.1294
3096	HIVEP1	A015-C-204	Human	Colorectum	FAP	2.46e-02	-4.64e-02	-0.0228
3096	HIVEP1	A002-C-201	Human	Colorectum	FAP	8.71e-08	-2.17e-01	0.0324
3096	HIVEP1	A002-C-203	Human	Colorectum	FAP	4.88e-02	-6.82e-02	0.2786
3096	HIVEP1	A001-C-108	Human	Colorectum	FAP	2.29e-17	-5.47e-02	-0.0272
3096	HIVEP1	A002-C-205	Human	Colorectum	FAP	4.40e-14	-1.51e-01	-0.1236

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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
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:00071786	Cervix	CC	transmembrane receptor protein serine/threonine kinase signaling pathway	67/2311	355/18723	2.39e-04	2.67e-03	67
GO:0007178	Colorectum	AD	transmembrane receptor protein serine/threonine kinase signaling pathway	99/3918	355/18723	9.92e-04	9.28e-03	99
GO:00071781	Colorectum	MSS	transmembrane receptor protein serine/threonine kinase signaling pathway	86/3467	355/18723	4.04e-03	2.95e-02	86
GO:00071782	Colorectum	FAP	transmembrane receptor protein serine/threonine kinase signaling pathway	81/2622	355/18723	4.28e-06	1.46e-04	81
GO:0071772	Colorectum	FAP	response to BMP	37/2622	165/18723	2.20e-03	1.80e-02	37
GO:0071773	Colorectum	FAP	cellular response to BMP stimulus	37/2622	165/18723	2.20e-03	1.80e-02	37
GO:0030509	Colorectum	FAP	BMP signaling pathway	34/2622	152/18723	3.38e-03	2.47e-02	34
GO:00071783	Colorectum	CRC	transmembrane receptor protein serine/threonine kinase signaling pathway	66/2078	355/18723	1.74e-05	5.28e-04	66
GO:00305091	Colorectum	CRC	BMP signaling pathway	31/2078	152/18723	5.73e-04	7.89e-03	31
GO:00717721	Colorectum	CRC	response to BMP	32/2078	165/18723	1.16e-03	1.33e-02	32
GO:00717731	Colorectum	CRC	cellular response to BMP stimulus	32/2078	165/18723	1.16e-03	1.33e-02	32
GO:00071787	Endometrium	AEH	transmembrane receptor protein serine/threonine kinase signaling pathway	67/2100	355/18723	1.28e-05	2.80e-04	67
GO:00305092	Endometrium	AEH	BMP signaling pathway	32/2100	152/18723	3.15e-04	3.54e-03	32
GO:00717722	Endometrium	AEH	response to BMP	32/2100	165/18723	1.38e-03	1.16e-02	32
GO:00717732	Endometrium	AEH	cellular response to BMP stimulus	32/2100	165/18723	1.38e-03	1.16e-02	32
GO:000717814	Endometrium	EEC	transmembrane receptor protein serine/threonine kinase signaling pathway	68/2168	355/18723	1.90e-05	3.50e-04	68
GO:003050911	Endometrium	EEC	BMP signaling pathway	32/2168	152/18723	5.52e-04	5.52e-03	32
GO:007177211	Endometrium	EEC	response to BMP	33/2168	165/18723	1.16e-03	9.90e-03	33
GO:007177311	Endometrium	EEC	cellular response to BMP stimulus	33/2168	165/18723	1.16e-03	9.90e-03	33
GO:000717810	Esophagus	ESCC	transmembrane receptor protein serine/threonine kinase signaling pathway	195/8552	355/18723	2.58e-04	1.58e-03	195

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
HIVEP1	CFIB	Colorectum	ADJ	PTPRD,UNC13C,MED12, etc.	4.30e-01
HIVEP1	CFIB	Colorectum	FAP	PTPRD,UNC13C,MED12, etc.	2.82e-01
HIVEP1	CFIB	Colorectum	Healthy	PTPRD,UNC13C,MED12, etc.	1.79e-01
HIVEP1	ECM	Colorectum	Healthy	PTPRD,UNC13C,MED12, etc.	1.40e-01
HIVEP1	STM	Endometrium	ADJ	HIVEP2,NFKB1,DENND4A, etc.	6.44e-01
HIVEP1	MSC	Liver	Cirrhotic	GPBP1,GMDS-DT,NUP153, etc.	2.63e-01
HIVEP1	LC	Lung	ADJ	SIPA1L1,HIVEP2,NFKB1, etc.	1.93e-01
HIVEP1	MALTB	Lung	MIAC	HIVEP2,ATP2B1,DLEU2, etc.	9.05e-02
HIVEP1	INCAF	Oral cavity	ADJ	DENND4A,RACK1,TRABD2B, etc.	8.43e-02
HIVEP1	ECM	Pancreas	PDAC	AFTPH,FP236383.3,NFKB1, etc.	2.53e-01

∗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

HIVEP1

SNV

Missense_Mutation

novel

c.6496N>G

p.Gln2166Glu

p.Q2166E

P15822

protein_coding

deleterious(0.02)

possibly_damaging(0.519)

TCGA-A2-A4RW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

HIVEP1

SNV

Missense_Mutation

rs753435750

c.125C>T

p.Ser42Leu

p.S42L

P15822

protein_coding

tolerated(0.12)

probably_damaging(0.918)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HIVEP1

SNV

Missense_Mutation

c.1148T>C

p.Val383Ala

p.V383A

P15822

protein_coding

deleterious(0.01)

probably_damaging(0.928)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HIVEP1

SNV

Missense_Mutation

rs373301856

c.4835C>T

p.Ser1612Leu

p.S1612L

P15822

protein_coding

tolerated(0.4)

benign(0.026)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HIVEP1

SNV

Missense_Mutation

c.5461N>T

p.Pro1821Ser

p.P1821S

P15822

protein_coding

tolerated(0.12)

probably_damaging(1)

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

HIVEP1

SNV

Missense_Mutation

rs371327892

c.4604N>T

p.Thr1535Met

p.T1535M

P15822

protein_coding

tolerated(0.09)

benign(0.202)

TCGA-AO-A0JM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

HIVEP1

SNV

Missense_Mutation

rs368115054

c.3794N>A

p.Arg1265His

p.R1265H

P15822

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AR-A0TS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

HIVEP1

SNV

Missense_Mutation

c.7345N>C

p.Ser2449Pro

p.S2449P

P15822

protein_coding

tolerated(0.38)

benign(0.024)

TCGA-AR-A1AL-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

anastrozole

HIVEP1

SNV

Missense_Mutation

c.2372N>G

p.Ser791Cys

p.S791C

P15822

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-B6-A0IJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HIVEP1

SNV

Missense_Mutation

rs746004351

c.1930G>A

p.Ala644Thr

p.A644T

P15822

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-BH-A0AW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

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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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