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: HERC1

Gene summary for HERC1

Gene summary.

Gene information	Species	Human
	Gene symbol	HERC1
	Gene ID	8925
	Gene name	HECT and RLD domain containing E3 ubiquitin protein ligase family member 1
	Gene Alias	MDFPMR
	Cytomap	15q22.31
	Gene Type	protein-coding
	GO ID	GO:0003008
	UniProtAcc	A0A024R5W0

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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
8925	HERC1	CA_HPV_1	Human	Cervix	CC	1.18e-05	-5.16e-02	0.0264
8925	HERC1	CCI_2	Human	Cervix	CC	4.20e-09	1.03e+00	0.5249
8925	HERC1	CCI_3	Human	Cervix	CC	3.79e-04	6.31e-01	0.516
8925	HERC1	HTA11_3410_2000001011	Human	Colorectum	AD	5.88e-15	-5.91e-01	0.0155
8925	HERC1	HTA11_3361_2000001011	Human	Colorectum	AD	3.57e-04	-5.05e-01	-0.1207
8925	HERC1	HTA11_696_2000001011	Human	Colorectum	AD	2.12e-02	-3.26e-01	-0.1464
8925	HERC1	HTA11_866_2000001011	Human	Colorectum	AD	8.88e-04	-3.58e-01	-0.1001
8925	HERC1	HTA11_866_3004761011	Human	Colorectum	AD	3.44e-08	-5.41e-01	0.096
8925	HERC1	HTA11_10711_2000001011	Human	Colorectum	AD	2.18e-02	-4.50e-01	0.0338
8925	HERC1	HTA11_7696_3000711011	Human	Colorectum	AD	1.06e-02	-3.30e-01	0.0674
8925	HERC1	HTA11_6818_2000001021	Human	Colorectum	AD	4.13e-03	-4.72e-01	0.0588
8925	HERC1	HTA11_99999970781_79442	Human	Colorectum	MSS	1.29e-12	-5.07e-01	0.294
8925	HERC1	HTA11_99999971662_82457	Human	Colorectum	MSS	6.08e-16	-5.71e-01	0.3859
8925	HERC1	HTA11_99999973899_84307	Human	Colorectum	MSS	1.32e-03	-5.68e-01	0.2585
8925	HERC1	HTA11_99999974143_84620	Human	Colorectum	MSS	1.70e-14	-5.43e-01	0.3005
8925	HERC1	A002-C-010	Human	Colorectum	FAP	1.68e-02	-2.25e-01	0.242
8925	HERC1	A001-C-207	Human	Colorectum	FAP	4.59e-05	-2.24e-01	0.1278
8925	HERC1	A015-C-203	Human	Colorectum	FAP	3.47e-30	-2.77e-01	-0.1294
8925	HERC1	A015-C-204	Human	Colorectum	FAP	1.12e-08	-3.82e-01	-0.0228
8925	HERC1	A014-C-040	Human	Colorectum	FAP	1.25e-05	-3.46e-01	-0.1184

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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
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
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:003133010	Cervix	CC	negative regulation of cellular catabolic process	63/2311	262/18723	1.10e-07	5.68e-06	63
GO:000989510	Cervix	CC	negative regulation of catabolic process	69/2311	320/18723	2.15e-06	6.55e-05	69
GO:00105067	Cervix	CC	regulation of autophagy	61/2311	317/18723	2.61e-04	2.87e-03	61
GO:0009895	Colorectum	AD	negative regulation of catabolic process	124/3918	320/18723	1.66e-13	3.35e-11	124
GO:0031330	Colorectum	AD	negative regulation of cellular catabolic process	104/3918	262/18723	2.66e-12	3.96e-10	104
GO:0010506	Colorectum	AD	regulation of autophagy	111/3918	317/18723	3.57e-09	2.35e-07	111
GO:0010507	Colorectum	AD	negative regulation of autophagy	31/3918	85/18723	6.91e-04	7.05e-03	31
GO:00313302	Colorectum	MSS	negative regulation of cellular catabolic process	96/3467	262/18723	2.67e-12	4.63e-10	96
GO:00098952	Colorectum	MSS	negative regulation of catabolic process	110/3467	320/18723	7.88e-12	1.20e-09	110
GO:00105062	Colorectum	MSS	regulation of autophagy	95/3467	317/18723	4.36e-07	1.71e-05	95
GO:00105071	Colorectum	MSS	negative regulation of autophagy	26/3467	85/18723	4.84e-03	3.38e-02	26
GO:00098954	Colorectum	FAP	negative regulation of catabolic process	91/2622	320/18723	9.66e-12	4.96e-09	91
GO:00313304	Colorectum	FAP	negative regulation of cellular catabolic process	77/2622	262/18723	6.79e-11	2.31e-08	77
GO:00105063	Colorectum	FAP	regulation of autophagy	80/2622	317/18723	6.43e-08	4.54e-06	80
GO:00105072	Colorectum	FAP	negative regulation of autophagy	24/2622	85/18723	4.59e-04	5.39e-03	24
GO:00098955	Colorectum	CRC	negative regulation of catabolic process	75/2078	320/18723	2.02e-10	9.31e-08	75
GO:00313305	Colorectum	CRC	negative regulation of cellular catabolic process	61/2078	262/18723	1.27e-08	2.54e-06	61
GO:00105064	Colorectum	CRC	regulation of autophagy	62/2078	317/18723	6.04e-06	2.35e-04	62
GO:00105073	Colorectum	CRC	negative regulation of autophagy	18/2078	85/18723	5.04e-03	3.87e-02	18
GO:0021953	Colorectum	CRC	central nervous system neuron differentiation	29/2078	162/18723	6.36e-03	4.62e-02	29

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0412014	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa0412015	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa04120	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041201	Colorectum	AD	Ubiquitin mediated proteolysis	58/2092	142/8465	1.46e-05	1.53e-04	9.76e-05	58
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041205	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa041206	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa041207	Colorectum	FAP	Ubiquitin mediated proteolysis	51/1404	142/8465	1.55e-08	5.84e-07	3.55e-07	51
hsa041208	Colorectum	CRC	Ubiquitin mediated proteolysis	42/1091	142/8465	9.98e-08	6.67e-06	4.52e-06	42
hsa041209	Colorectum	CRC	Ubiquitin mediated proteolysis	42/1091	142/8465	9.98e-08	6.67e-06	4.52e-06	42
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0412036	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0412010	Liver	NAFLD	Ubiquitin mediated proteolysis	44/1043	142/8465	2.59e-09	1.70e-07	1.37e-07	44
hsa0412011	Liver	NAFLD	Ubiquitin mediated proteolysis	44/1043	142/8465	2.59e-09	1.70e-07	1.37e-07	44
hsa0412041	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa0412051	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa0412012	Lung	IAC	Ubiquitin mediated proteolysis	40/1053	142/8465	3.24e-07	1.76e-05	1.17e-05	40
hsa0412013	Lung	IAC	Ubiquitin mediated proteolysis	40/1053	142/8465	3.24e-07	1.76e-05	1.17e-05	40
hsa0412022	Lung	AIS	Ubiquitin mediated proteolysis	41/961	142/8465	8.01e-09	4.33e-07	2.77e-07	41
hsa0412032	Lung	AIS	Ubiquitin mediated proteolysis	41/961	142/8465	8.01e-09	4.33e-07	2.77e-07	41

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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

HERC1

SNV

Missense_Mutation

novel

c.11710N>A

p.Pro3904Thr

p.P3904T

Q15751

protein_coding

deleterious(0.03)

probably_damaging(0.994)

TCGA-A7-A3J0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

anastrazole

HERC1

SNV

Missense_Mutation

novel

c.1118N>T

p.Glu373Val

p.E373V

Q15751

protein_coding

tolerated(0.06)

benign(0.376)

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

HERC1

SNV

Missense_Mutation

c.8243N>T

p.Pro2748Leu

p.P2748L

Q15751

protein_coding

tolerated(0.08)

probably_damaging(0.996)

TCGA-A8-A08B-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

HERC1

SNV

Missense_Mutation

c.8878G>C

p.Glu2960Gln

p.E2960Q

Q15751

protein_coding

tolerated(0.05)

probably_damaging(0.979)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HERC1

SNV

Missense_Mutation

c.3290G>A

p.Arg1097Lys

p.R1097K

Q15751

protein_coding

tolerated(0.48)

benign(0.003)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HERC1

SNV

Missense_Mutation

novel

c.1382N>T

p.Ser461Leu

p.S461L

Q15751

protein_coding

deleterious(0)

possibly_damaging(0.448)

TCGA-AC-A8OQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HERC1

SNV

Missense_Mutation

novel

c.13958C>A

p.Ser4653Tyr

p.S4653Y

Q15751

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HERC1

SNV

Missense_Mutation

rs748693076

c.13771C>T

p.Arg4591Cys

p.R4591C

Q15751

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HERC1

SNV

Missense_Mutation

rs774633591

c.11846C>A

p.Ser3949Tyr

p.S3949Y

Q15751

protein_coding

deleterious(0)

benign(0.259)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HERC1

SNV

Missense_Mutation

rs757745102

c.4529C>T

p.Ser1510Leu

p.S1510L

Q15751

protein_coding

tolerated(0.13)

probably_damaging(0.921)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

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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