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: TRIM33

Gene summary for TRIM33

Gene summary.

Gene information	Species	Human
	Gene symbol	TRIM33
	Gene ID	51592
	Gene name	tripartite motif containing 33
	Gene Alias	ECTO
	Cytomap	1p13.2
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	B3KN30

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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
51592	TRIM33	HTA11_3410_2000001011	Human	Colorectum	AD	2.76e-09	-4.08e-01	0.0155
51592	TRIM33	HTA11_866_3004761011	Human	Colorectum	AD	1.57e-02	-3.47e-01	0.096
51592	TRIM33	HTA11_7696_3000711011	Human	Colorectum	AD	1.90e-05	-2.68e-01	0.0674
51592	TRIM33	HTA11_99999974143_84620	Human	Colorectum	MSS	2.87e-05	-2.99e-01	0.3005
51592	TRIM33	A001-C-207	Human	Colorectum	FAP	1.95e-05	-2.68e-01	0.1278
51592	TRIM33	A015-C-203	Human	Colorectum	FAP	4.38e-30	-3.16e-01	-0.1294
51592	TRIM33	A015-C-204	Human	Colorectum	FAP	6.80e-12	-3.84e-01	-0.0228
51592	TRIM33	A014-C-040	Human	Colorectum	FAP	2.62e-07	-4.83e-01	-0.1184
51592	TRIM33	A002-C-201	Human	Colorectum	FAP	2.25e-17	-3.29e-01	0.0324
51592	TRIM33	A002-C-203	Human	Colorectum	FAP	2.07e-06	-2.61e-01	0.2786
51592	TRIM33	A001-C-119	Human	Colorectum	FAP	1.23e-12	-5.37e-01	-0.1557
51592	TRIM33	A001-C-108	Human	Colorectum	FAP	1.01e-18	-2.56e-01	-0.0272
51592	TRIM33	A002-C-205	Human	Colorectum	FAP	1.16e-24	-3.32e-01	-0.1236
51592	TRIM33	A001-C-104	Human	Colorectum	FAP	1.42e-06	-2.88e-01	0.0184
51592	TRIM33	A015-C-005	Human	Colorectum	FAP	4.05e-05	-2.23e-01	-0.0336
51592	TRIM33	A015-C-006	Human	Colorectum	FAP	4.37e-16	-3.54e-01	-0.0994
51592	TRIM33	A015-C-106	Human	Colorectum	FAP	2.03e-15	-1.88e-01	-0.0511
51592	TRIM33	A002-C-114	Human	Colorectum	FAP	3.15e-21	-3.97e-01	-0.1561
51592	TRIM33	A015-C-104	Human	Colorectum	FAP	1.17e-32	-4.17e-01	-0.1899
51592	TRIM33	A001-C-014	Human	Colorectum	FAP	1.59e-14	-3.21e-01	0.0135

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0007178	Colorectum	AD	transmembrane receptor protein serine/threonine kinase signaling pathway	99/3918	355/18723	9.92e-04	9.28e-03	99
GO:0071559	Colorectum	AD	response to transforming growth factor beta	74/3918	256/18723	1.45e-03	1.23e-02	74
GO:0071560	Colorectum	AD	cellular response to transforming growth factor beta stimulus	72/3918	250/18723	1.85e-03	1.52e-02	72
GO:0007179	Colorectum	AD	transforming growth factor beta receptor signaling pathway	59/3918	198/18723	1.94e-03	1.58e-02	59
GO:00071781	Colorectum	MSS	transmembrane receptor protein serine/threonine kinase signaling pathway	86/3467	355/18723	4.04e-03	2.95e-02	86
GO:00715591	Colorectum	FAP	response to transforming growth factor beta	63/2622	256/18723	3.82e-06	1.32e-04	63
GO:00071782	Colorectum	FAP	transmembrane receptor protein serine/threonine kinase signaling pathway	81/2622	355/18723	4.28e-06	1.46e-04	81
GO:00715601	Colorectum	FAP	cellular response to transforming growth factor beta stimulus	61/2622	250/18723	7.22e-06	2.19e-04	61
GO:00071791	Colorectum	FAP	transforming growth factor beta receptor signaling pathway	50/2622	198/18723	1.75e-05	4.44e-04	50
GO:0017015	Colorectum	FAP	regulation of transforming growth factor beta receptor signaling pathway	31/2622	128/18723	1.35e-03	1.24e-02	31
GO:1903844	Colorectum	FAP	regulation of cellular response to transforming growth factor beta stimulus	31/2622	131/18723	2.01e-03	1.67e-02	31
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:0090092	Colorectum	FAP	regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	52/2622	256/18723	3.33e-03	2.44e-02	52
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:00715592	Colorectum	CRC	response to transforming growth factor beta	51/2078	256/18723	2.33e-05	6.65e-04	51
GO:00715602	Colorectum	CRC	cellular response to transforming growth factor beta stimulus	49/2078	250/18723	5.17e-05	1.19e-03	49
GO:00071792	Colorectum	CRC	transforming growth factor beta receptor signaling pathway	39/2078	198/18723	2.58e-04	4.19e-03	39
GO:00305091	Colorectum	CRC	BMP signaling pathway	31/2078	152/18723	5.73e-04	7.89e-03	31

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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

TRIM33

SNV

Missense_Mutation

novel

c.2950N>A

p.Glu984Lys

p.E984K

Q9UPN9

protein_coding

tolerated(0.19)

benign(0.049)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

TRIM33

SNV

Missense_Mutation

novel

c.2134N>A

p.Gln712Lys

p.Q712K

Q9UPN9

protein_coding

tolerated(1)

benign(0.191)

TCGA-AN-A03Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TRIM33

SNV

Missense_Mutation

c.2923N>C

p.Cys975Arg

p.C975R

Q9UPN9

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AR-A255-01

Breast

breast invasive carcinoma

Female

<65

I/II

Targeted Molecular therapy

trastuzumab

TRIM33

SNV

Missense_Mutation

novel

c.3162N>G

p.Ile1054Met

p.I1054M

Q9UPN9

protein_coding

tolerated(0.05)

possibly_damaging(0.674)

TCGA-BH-A0DI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TRIM33

insertion

Nonsense_Mutation

novel

c.1321_1322insCAGAAAGAGCTTTTTAAAATA

p.His441delinsProGluArgAlaPheTerAsnAsn

p.H441delinsPERAF*NN

Q9UPN9

protein_coding

TCGA-A8-A0A4-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

TRIM33

SNV

Missense_Mutation

novel

c.3079N>A

p.Asp1027Asn

p.D1027N

Q9UPN9

protein_coding

deleterious(0.02)

probably_damaging(0.998)

TCGA-C5-A7X5-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

carboplatin

TRIM33

SNV

Missense_Mutation

c.3363G>C

p.Glu1121Asp

p.E1121D

Q9UPN9

protein_coding

tolerated(0.31)

benign(0.007)

TCGA-EK-A2PG-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

TRIM33

SNV

Missense_Mutation

novel

c.3301N>A

p.Val1101Ile

p.V1101I

Q9UPN9

protein_coding

tolerated(0.45)

benign(0)

TCGA-5M-AAT6-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Unknown

TRIM33

SNV

Missense_Mutation

c.1154A>T

p.Glu385Val

p.E385V

Q9UPN9

protein_coding

deleterious(0)

possibly_damaging(0.874)

TCGA-A6-2686-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

TRIM33

SNV

Missense_Mutation

novel

c.2045N>C

p.Asp682Ala

p.D682A

Q9UPN9

protein_coding

deleterious(0)

possibly_damaging(0.837)

TCGA-A6-6141-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

5-fu

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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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