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: CAND1

Gene summary for CAND1

Gene summary.

Gene information	Species	Human
	Gene symbol	CAND1
	Gene ID	55832
	Gene name	cullin associated and neddylation dissociated 1
	Gene Alias	TIP120
	Cytomap	12q14.3-q15
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	Q86VP6

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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
55832	CAND1	LZE4T	Human	Esophagus	ESCC	3.48e-16	6.63e-01	0.0811
55832	CAND1	LZE7T	Human	Esophagus	ESCC	1.73e-12	8.60e-01	0.0667
55832	CAND1	LZE8T	Human	Esophagus	ESCC	6.56e-08	6.46e-02	0.067
55832	CAND1	LZE20T	Human	Esophagus	ESCC	4.56e-08	1.31e-01	0.0662
55832	CAND1	LZE24T	Human	Esophagus	ESCC	3.18e-18	4.63e-01	0.0596
55832	CAND1	LZE21T	Human	Esophagus	ESCC	5.70e-05	1.76e-01	0.0655
55832	CAND1	LZE6T	Human	Esophagus	ESCC	1.80e-02	5.51e-02	0.0845
55832	CAND1	P1T-E	Human	Esophagus	ESCC	3.12e-13	1.05e+00	0.0875
55832	CAND1	P2T-E	Human	Esophagus	ESCC	5.21e-87	1.36e+00	0.1177
55832	CAND1	P4T-E	Human	Esophagus	ESCC	6.60e-26	4.23e-01	0.1323
55832	CAND1	P5T-E	Human	Esophagus	ESCC	7.15e-28	4.47e-01	0.1327
55832	CAND1	P8T-E	Human	Esophagus	ESCC	1.07e-45	7.33e-01	0.0889
55832	CAND1	P9T-E	Human	Esophagus	ESCC	4.80e-12	2.73e-01	0.1131
55832	CAND1	P10T-E	Human	Esophagus	ESCC	1.55e-53	7.98e-01	0.116
55832	CAND1	P11T-E	Human	Esophagus	ESCC	3.63e-20	8.56e-01	0.1426
55832	CAND1	P12T-E	Human	Esophagus	ESCC	1.42e-54	9.56e-01	0.1122
55832	CAND1	P15T-E	Human	Esophagus	ESCC	7.83e-25	5.79e-01	0.1149
55832	CAND1	P16T-E	Human	Esophagus	ESCC	2.93e-49	7.20e-01	0.1153
55832	CAND1	P17T-E	Human	Esophagus	ESCC	2.51e-08	5.37e-01	0.1278
55832	CAND1	P19T-E	Human	Esophagus	ESCC	1.38e-05	6.02e-01	0.1662

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0043254111	Esophagus	ESCC	regulation of protein-containing complex assembly	278/8552	428/18723	3.81e-16	2.77e-14	278
GO:0031334111	Esophagus	ESCC	positive regulation of protein-containing complex assembly	166/8552	237/18723	2.06e-14	1.07e-12	166
GO:00063673	Esophagus	ESCC	transcription initiation from RNA polymerase II promoter	56/8552	77/18723	1.30e-06	1.59e-05	56
GO:000635211	Esophagus	ESCC	DNA-templated transcription, initiation	86/8552	130/18723	1.88e-06	2.19e-05	86
GO:00708973	Esophagus	ESCC	transcription preinitiation complex assembly	30/8552	36/18723	3.60e-06	3.95e-05	30
GO:00602603	Esophagus	ESCC	regulation of transcription initiation from RNA polymerase II promoter	25/8552	33/18723	4.30e-04	2.43e-03	25
GO:200014212	Esophagus	ESCC	regulation of DNA-templated transcription, initiation	29/8552	40/18723	5.32e-04	2.93e-03	29
GO:00511232	Esophagus	ESCC	RNA polymerase II preinitiation complex assembly	18/8552	24/18723	3.43e-03	1.41e-02	18
GO:20001443	Esophagus	ESCC	positive regulation of DNA-templated transcription, initiation	21/8552	31/18723	1.10e-02	3.70e-02	21
GO:004325412	Liver	Cirrhotic	regulation of protein-containing complex assembly	169/4634	428/18723	7.40e-12	4.99e-10	169
GO:00313347	Liver	Cirrhotic	positive regulation of protein-containing complex assembly	95/4634	237/18723	1.21e-07	3.39e-06	95
GO:0006367	Liver	Cirrhotic	transcription initiation from RNA polymerase II promoter	31/4634	77/18723	1.91e-03	1.20e-02	31
GO:0070897	Liver	Cirrhotic	transcription preinitiation complex assembly	17/4634	36/18723	2.82e-03	1.63e-02	17
GO:0051123	Liver	Cirrhotic	RNA polymerase II preinitiation complex assembly	12/4634	24/18723	6.58e-03	3.25e-02	12
GO:0060260	Liver	Cirrhotic	regulation of transcription initiation from RNA polymerase II promoter	15/4634	33/18723	7.61e-03	3.60e-02	15
GO:2000142	Liver	Cirrhotic	regulation of DNA-templated transcription, initiation	17/4634	40/18723	1.04e-02	4.61e-02	17
GO:004325422	Liver	HCC	regulation of protein-containing complex assembly	264/7958	428/18723	5.47e-16	4.39e-14	264
GO:003133412	Liver	HCC	positive regulation of protein-containing complex assembly	150/7958	237/18723	7.35e-11	2.63e-09	150
GO:00063671	Liver	HCC	transcription initiation from RNA polymerase II promoter	52/7958	77/18723	7.87e-06	9.27e-05	52
GO:0006352	Liver	HCC	DNA-templated transcription, initiation	78/7958	130/18723	4.19e-05	4.11e-04	78

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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

CAND1

SNV

Missense_Mutation

c.486N>C

p.Leu162Phe

p.L162F

Q86VP6

protein_coding

deleterious(0.01)

benign(0.384)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CAND1

SNV

Missense_Mutation

novel

c.3425N>C

p.Leu1142Ser

p.L1142S

Q86VP6

protein_coding

deleterious(0)

probably_damaging(0.971)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CAND1

SNV

Missense_Mutation

rs199801743

c.3152A>G

p.His1051Arg

p.H1051R

Q86VP6

protein_coding

tolerated(0.42)

benign(0.007)

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

CAND1

SNV

Missense_Mutation

c.520N>T

p.Pro174Ser

p.P174S

Q86VP6

protein_coding

tolerated(1)

benign(0.003)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CAND1

SNV

Missense_Mutation

rs773906312

c.1673C>T

p.Ser558Leu

p.S558L

Q86VP6

protein_coding

tolerated(0.31)

benign(0)

TCGA-BH-A0DK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

CAND1

SNV

Missense_Mutation

c.292N>A

p.Asp98Asn

p.D98N

Q86VP6

protein_coding

tolerated(0.2)

benign(0.055)

TCGA-BH-A18U-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

CAND1

SNV

Missense_Mutation

c.541N>T

p.Leu181Phe

p.L181F

Q86VP6

protein_coding

deleterious(0.03)

possibly_damaging(0.839)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CAND1

insertion

Frame_Shift_Ins

novel

c.2485_2486insACCAGAGAGCTTTGAAACTGGGTACTCTTTCTGCCCTT

p.Arg829AsnfsTer22

p.R829Nfs*22

Q86VP6

protein_coding

TCGA-A8-A09E-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

CAND1

insertion

Nonsense_Mutation

novel

c.3349_3350insA

p.Tyr1117Ter

p.Y1117*

Q86VP6

protein_coding

TCGA-AO-A0JE-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

CAND1

insertion

Frame_Shift_Ins

novel

c.3154_3155insAACTGGTG

p.Leu1052GlnfsTer15

p.L1052Qfs*15

Q86VP6

protein_coding

TCGA-AO-A128-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

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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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