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: CRB3

Gene summary for CRB3

Gene summary.

Gene information	Species	Human
	Gene symbol	CRB3
	Gene ID	92359
	Gene name	crumbs cell polarity complex component 3
	Gene Alias	CRB3
	Cytomap	19p13.3
	Gene Type	protein-coding
	GO ID	GO:0008104
	UniProtAcc	Q9BUF7

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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
92359	CRB3	LZE4T	Human	Esophagus	ESCC	2.64e-16	3.85e-01	0.0811
92359	CRB3	LZE5T	Human	Esophagus	ESCC	6.58e-03	4.10e-01	0.0514
92359	CRB3	LZE7T	Human	Esophagus	ESCC	9.04e-10	5.64e-01	0.0667
92359	CRB3	LZE20T	Human	Esophagus	ESCC	1.47e-02	2.26e-01	0.0662
92359	CRB3	LZE22D1	Human	Esophagus	HGIN	3.44e-03	1.82e-01	0.0595
92359	CRB3	LZE24T	Human	Esophagus	ESCC	3.24e-33	9.83e-01	0.0596
92359	CRB3	LZE21T	Human	Esophagus	ESCC	3.26e-05	6.36e-01	0.0655
92359	CRB3	LZE6T	Human	Esophagus	ESCC	5.71e-06	2.40e-01	0.0845
92359	CRB3	P1T-E	Human	Esophagus	ESCC	5.83e-14	1.05e+00	0.0875
92359	CRB3	P2T-E	Human	Esophagus	ESCC	7.93e-10	2.27e-01	0.1177
92359	CRB3	P4T-E	Human	Esophagus	ESCC	1.27e-47	1.06e+00	0.1323
92359	CRB3	P5T-E	Human	Esophagus	ESCC	8.48e-43	8.52e-01	0.1327
92359	CRB3	P8T-E	Human	Esophagus	ESCC	5.95e-31	6.79e-01	0.0889
92359	CRB3	P9T-E	Human	Esophagus	ESCC	2.53e-16	4.96e-01	0.1131
92359	CRB3	P10T-E	Human	Esophagus	ESCC	2.33e-16	2.26e-01	0.116
92359	CRB3	P11T-E	Human	Esophagus	ESCC	5.21e-06	2.93e-01	0.1426
92359	CRB3	P12T-E	Human	Esophagus	ESCC	3.59e-29	4.51e-01	0.1122
92359	CRB3	P15T-E	Human	Esophagus	ESCC	6.14e-20	5.36e-01	0.1149
92359	CRB3	P16T-E	Human	Esophagus	ESCC	7.12e-22	1.82e-01	0.1153
92359	CRB3	P17T-E	Human	Esophagus	ESCC	1.99e-20	6.59e-01	0.1278

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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
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:007265920	Esophagus	HGIN	protein localization to plasma membrane	66/2587	284/18723	1.11e-05	3.18e-04	66
GO:199077818	Esophagus	HGIN	protein localization to cell periphery	71/2587	333/18723	1.05e-04	2.24e-03	71
GO:0072659110	Esophagus	ESCC	protein localization to plasma membrane	193/8552	284/18723	1.95e-14	1.03e-12	193
GO:199077819	Esophagus	ESCC	protein localization to cell periphery	217/8552	333/18723	4.08e-13	1.88e-11	217
GO:003432918	Esophagus	ESCC	cell junction assembly	227/8552	420/18723	3.06e-04	1.83e-03	227
GO:190188810	Esophagus	ESCC	regulation of cell junction assembly	109/8552	204/18723	1.53e-02	4.96e-02	109
GO:199077811	Liver	Cirrhotic	protein localization to cell periphery	135/4634	333/18723	1.18e-10	6.21e-09	135
GO:007265911	Liver	Cirrhotic	protein localization to plasma membrane	119/4634	284/18723	1.30e-10	6.80e-09	119
GO:007265921	Liver	HCC	protein localization to plasma membrane	177/7958	284/18723	1.02e-11	4.18e-10	177
GO:199077821	Liver	HCC	protein localization to cell periphery	200/7958	333/18723	6.07e-11	2.23e-09	200
GO:007265918	Oral cavity	OSCC	protein localization to plasma membrane	169/7305	284/18723	1.69e-12	7.21e-11	169
GO:199077816	Oral cavity	OSCC	protein localization to cell periphery	190/7305	333/18723	1.46e-11	5.13e-10	190
GO:003432916	Oral cavity	OSCC	cell junction assembly	190/7305	420/18723	4.99e-03	1.96e-02	190
GO:007265916	Prostate	BPH	protein localization to plasma membrane	89/3107	284/18723	5.00e-10	2.56e-08	89
GO:003432910	Prostate	BPH	cell junction assembly	114/3107	420/18723	2.52e-08	7.49e-07	114
GO:199077810	Prostate	BPH	protein localization to cell periphery	95/3107	333/18723	2.78e-08	8.13e-07	95
GO:19018888	Prostate	BPH	regulation of cell junction assembly	62/3107	204/18723	6.71e-07	1.30e-05	62
GO:1901890	Prostate	BPH	positive regulation of cell junction assembly	28/3107	104/18723	5.18e-03	2.43e-02	28
GO:007265917	Prostate	Tumor	protein localization to plasma membrane	90/3246	284/18723	2.07e-09	8.99e-08	90
GO:199077815	Prostate	Tumor	protein localization to cell periphery	97/3246	333/18723	5.88e-08	1.75e-06	97

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0453039	Esophagus	HGIN	Tight junction	40/1383	169/8465	8.18e-03	4.71e-02	3.74e-02	40
hsa04530115	Esophagus	HGIN	Tight junction	40/1383	169/8465	8.18e-03	4.71e-02	3.74e-02	40
hsa0516510	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa04530211	Esophagus	ESCC	Tight junction	105/4205	169/8465	6.73e-04	2.23e-03	1.14e-03	105
hsa0516515	Esophagus	ESCC	Human papillomavirus infection	215/4205	331/8465	7.86e-09	7.12e-08	3.65e-08	215
hsa04530310	Esophagus	ESCC	Tight junction	105/4205	169/8465	6.73e-04	2.23e-03	1.14e-03	105
hsa0453022	Liver	Cirrhotic	Tight junction	82/2530	169/8465	2.14e-07	2.85e-06	1.76e-06	82
hsa05165	Liver	Cirrhotic	Human papillomavirus infection	124/2530	331/8465	1.55e-03	7.83e-03	4.83e-03	124
hsa0453032	Liver	Cirrhotic	Tight junction	82/2530	169/8465	2.14e-07	2.85e-06	1.76e-06	82
hsa051651	Liver	Cirrhotic	Human papillomavirus infection	124/2530	331/8465	1.55e-03	7.83e-03	4.83e-03	124
hsa0453042	Liver	HCC	Tight junction	110/4020	169/8465	2.45e-06	2.28e-05	1.27e-05	110
hsa051652	Liver	HCC	Human papillomavirus infection	188/4020	331/8465	3.34e-04	1.49e-03	8.29e-04	188
hsa0453052	Liver	HCC	Tight junction	110/4020	169/8465	2.45e-06	2.28e-05	1.27e-05	110
hsa051653	Liver	HCC	Human papillomavirus infection	188/4020	331/8465	3.34e-04	1.49e-03	8.29e-04	188
hsa051659	Oral cavity	OSCC	Human papillomavirus infection	200/3704	331/8465	3.83e-10	4.93e-09	2.51e-09	200
hsa0453030	Oral cavity	OSCC	Tight junction	102/3704	169/8465	8.68e-06	3.93e-05	2.00e-05	102
hsa0516514	Oral cavity	OSCC	Human papillomavirus infection	200/3704	331/8465	3.83e-10	4.93e-09	2.51e-09	200
hsa04530114	Oral cavity	OSCC	Tight junction	102/3704	169/8465	8.68e-06	3.93e-05	2.00e-05	102
hsa0453028	Prostate	BPH	Tight junction	68/1718	169/8465	1.70e-09	2.55e-08	1.58e-08	68
hsa051658	Prostate	BPH	Human papillomavirus infection	111/1718	331/8465	6.15e-09	7.81e-08	4.83e-08	111

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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

CRB3

SNV

Missense_Mutation

c.84N>G

p.Ile28Met

p.I28M

Q9BUF7

protein_coding

tolerated_low_confidence(0.14)

benign(0)

TCGA-D5-6540-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

CRB3

SNV

Missense_Mutation

c.220N>A

p.Val74Met

p.V74M

Q9BUF7

protein_coding

tolerated(0.1)

benign(0.316)

TCGA-WS-AB45-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

CRB3

SNV

Missense_Mutation

novel

c.131C>T

p.Thr44Ile

p.T44I

Q9BUF7

protein_coding

deleterious(0.03)

benign(0.082)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

CRB3

SNV

Missense_Mutation

rs369374366

c.266N>T

p.Thr89Met

p.T89M

Q9BUF7

protein_coding

deleterious(0)

possibly_damaging(0.883)

TCGA-AX-A3FS-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CRB3

SNV

Missense_Mutation

rs748268475

c.316G>A

p.Glu106Lys

p.E106K

Q9BUF7

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.963)

TCGA-BK-A0C9-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CRB3

SNV

Missense_Mutation

novel

c.188N>C

p.Val63Ala

p.V63A

Q9BUF7

protein_coding

deleterious(0.03)

probably_damaging(0.979)

TCGA-D1-A175-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

paclitaxel

CRB3

SNV

Missense_Mutation

novel

c.58N>G

p.Arg20Gly

p.R20G

Q9BUF7

protein_coding

tolerated_low_confidence(0.28)

benign(0.005)

TCGA-DD-AADC-01

Liver

liver hepatocellular carcinoma

Male

<65

I/II

Unknown

CRB3

SNV

Missense_Mutation

rs754598571

c.241C>T

p.Arg81Trp

p.R81W

Q9BUF7

protein_coding

deleterious(0.04)

benign(0.007)

TCGA-63-A5MM-01

Lung

lung squamous cell carcinoma

Female

>=65

I/II

Chemotherapy

cisplatin

CRB3

SNV

Missense_Mutation

rs751295212

c.292G>A

p.Glu98Lys

p.E98K

Q9BUF7

protein_coding

deleterious(0)

probably_damaging(0.974)

TCGA-CN-4734-01

Oral cavity

head & neck squamous cell carcinoma

Male

>=65

I/II

Unknown

CRB3

SNV

Missense_Mutation

novel

c.143N>G

p.Ser48Cys

p.S48C

Q9BUF7

protein_coding

deleterious(0)

possibly_damaging(0.634)

TCGA-CR-7388-01

Oral cavity

head & neck squamous cell 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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