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: HECW2

Gene summary for HECW2

Gene summary.

Gene information	Species	Human
	Gene symbol	HECW2
	Gene ID	57520
	Gene name	HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2
	Gene Alias	NDHSAL
	Cytomap	2q32.3
	Gene Type	protein-coding
	GO ID	GO:0000070
	UniProtAcc	A0A2C9F2N4

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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
57520	HECW2	ATC11	Human	Thyroid	ATC	1.80e-12	8.48e-01	0.3386
57520	HECW2	ATC12	Human	Thyroid	ATC	1.13e-11	2.47e-01	0.34
57520	HECW2	ATC3	Human	Thyroid	ATC	2.42e-14	7.06e-01	0.338
57520	HECW2	ATC4	Human	Thyroid	ATC	3.34e-18	3.50e-01	0.34

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:001049832	Thyroid	ATC	proteasomal protein catabolic process	309/6293	490/18723	1.78e-41	1.13e-37	309
GO:0043161210	Thyroid	ATC	proteasome-mediated ubiquitin-dependent protein catabolic process	265/6293	412/18723	7.09e-38	1.49e-34	265
GO:0009896210	Thyroid	ATC	positive regulation of catabolic process	290/6293	492/18723	2.15e-31	1.94e-28	290
GO:004217635	Thyroid	ATC	regulation of protein catabolic process	239/6293	391/18723	2.63e-29	1.85e-26	239
GO:0045732210	Thyroid	ATC	positive regulation of protein catabolic process	148/6293	231/18723	1.93e-21	4.36e-19	148
GO:014001416	Thyroid	ATC	mitotic nuclear division	171/6293	287/18723	1.13e-19	1.66e-17	171
GO:003304423	Thyroid	ATC	regulation of chromosome organization	119/6293	187/18723	3.55e-17	3.40e-15	119
GO:004477219	Thyroid	ATC	mitotic cell cycle phase transition	223/6293	424/18723	3.46e-16	2.88e-14	223
GO:000007013	Thyroid	ATC	mitotic sister chromatid segregation	108/6293	168/18723	3.53e-16	2.90e-14	108
GO:000734622	Thyroid	ATC	regulation of mitotic cell cycle	236/6293	457/18723	7.58e-16	5.92e-14	236
GO:000081913	Thyroid	ATC	sister chromatid segregation	122/6293	202/18723	4.71e-15	3.17e-13	122
GO:000705913	Thyroid	ATC	chromosome segregation	183/6293	346/18723	8.03e-14	4.23e-12	183
GO:0000209110	Thyroid	ATC	protein polyubiquitination	134/6293	236/18723	1.86e-13	9.20e-12	134
GO:190199015	Thyroid	ATC	regulation of mitotic cell cycle phase transition	156/6293	299/18723	2.19e-11	7.80e-10	156
GO:005198311	Thyroid	ATC	regulation of chromosome segregation	60/6293	91/18723	2.83e-10	8.10e-09	60
GO:009881312	Thyroid	ATC	nuclear chromosome segregation	145/6293	281/18723	3.06e-10	8.61e-09	145
GO:003007111	Thyroid	ATC	regulation of mitotic metaphase/anaphase transition	44/6293	60/18723	3.54e-10	9.86e-09	44
GO:000709111	Thyroid	ATC	metaphase/anaphase transition of mitotic cell cycle	45/6293	62/18723	3.93e-10	1.08e-08	45
GO:001097523	Thyroid	ATC	regulation of neuron projection development	212/6293	445/18723	4.16e-10	1.14e-08	212
GO:004828512	Thyroid	ATC	organelle fission	229/6293	488/18723	4.79e-10	1.29e-08	229

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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

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

HECW2

SNV

Missense_Mutation

c.3028N>G

p.Thr1010Ala

p.T1010A

Q9P2P5

protein_coding

tolerated(1)

benign(0.012)

TCGA-A2-A04R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

HECW2

SNV

Missense_Mutation

novel

c.3629N>C

p.Gly1210Ala

p.G1210A

Q9P2P5

protein_coding

deleterious(0.04)

probably_damaging(0.996)

TCGA-A7-A4SE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

HECW2

SNV

Missense_Mutation

c.2051N>C

p.Cys684Ser

p.C684S

Q9P2P5

protein_coding

tolerated_low_confidence(0.8)

benign(0.011)

TCGA-A8-A094-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HECW2

SNV

Missense_Mutation

c.1390N>A

p.Asp464Asn

p.D464N

Q9P2P5

protein_coding

deleterious_low_confidence(0.02)

probably_damaging(0.989)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HECW2

SNV

Missense_Mutation

c.403N>A

p.Glu135Lys

p.E135K

Q9P2P5

protein_coding

deleterious(0)

probably_damaging(0.977)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HECW2

SNV

Missense_Mutation

c.76N>A

p.Glu26Lys

p.E26K

Q9P2P5

protein_coding

deleterious_low_confidence(0.01)

benign(0.395)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HECW2

SNV

Missense_Mutation

c.1270N>A

p.Glu424Lys

p.E424K

Q9P2P5

protein_coding

deleterious_low_confidence(0.01)

benign(0.028)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HECW2

SNV

Missense_Mutation

c.3726G>C

p.Gln1242His

p.Q1242H

Q9P2P5

protein_coding

deleterious(0.04)

probably_damaging(0.986)

TCGA-AR-A0TX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HECW2

SNV

Missense_Mutation

rs776128886

c.59N>A

p.Arg20Gln

p.R20Q

Q9P2P5

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.978)

TCGA-AR-A256-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

HECW2

SNV

Missense_Mutation

novel

c.739G>A

p.Glu247Lys

p.E247K

Q9P2P5

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AR-A2LE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

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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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