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: TRAF3

Gene summary for TRAF3

Gene summary.

Gene information	Species	Human
	Gene symbol	TRAF3
	Gene ID	7187
	Gene name	TNF receptor associated factor 3
	Gene Alias	CAP-1
	Cytomap	14q32.32
	Gene Type	protein-coding
	GO ID	GO:0000165
	UniProtAcc	Q13114

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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
7187	TRAF3	CCI_1	Human	Cervix	CC	5.87e-10	8.68e-01	0.528
7187	TRAF3	CCI_3	Human	Cervix	CC	8.19e-07	6.75e-01	0.516
7187	TRAF3	LZE7T	Human	Esophagus	ESCC	2.33e-03	2.19e-01	0.0667
7187	TRAF3	P2T-E	Human	Esophagus	ESCC	3.22e-22	3.82e-01	0.1177
7187	TRAF3	P4T-E	Human	Esophagus	ESCC	1.64e-11	2.45e-01	0.1323
7187	TRAF3	P5T-E	Human	Esophagus	ESCC	8.07e-11	1.30e-01	0.1327
7187	TRAF3	P8T-E	Human	Esophagus	ESCC	2.25e-08	1.02e-01	0.0889
7187	TRAF3	P9T-E	Human	Esophagus	ESCC	3.00e-05	1.18e-01	0.1131
7187	TRAF3	P10T-E	Human	Esophagus	ESCC	1.55e-03	1.39e-01	0.116
7187	TRAF3	P11T-E	Human	Esophagus	ESCC	1.50e-04	1.43e-01	0.1426
7187	TRAF3	P12T-E	Human	Esophagus	ESCC	8.48e-12	1.65e-01	0.1122
7187	TRAF3	P15T-E	Human	Esophagus	ESCC	3.10e-06	1.44e-01	0.1149
7187	TRAF3	P16T-E	Human	Esophagus	ESCC	4.63e-09	1.90e-01	0.1153
7187	TRAF3	P21T-E	Human	Esophagus	ESCC	1.03e-10	1.50e-01	0.1617
7187	TRAF3	P22T-E	Human	Esophagus	ESCC	2.09e-08	9.27e-02	0.1236
7187	TRAF3	P23T-E	Human	Esophagus	ESCC	1.35e-06	1.78e-01	0.108
7187	TRAF3	P24T-E	Human	Esophagus	ESCC	1.50e-08	1.37e-01	0.1287
7187	TRAF3	P26T-E	Human	Esophagus	ESCC	2.68e-21	2.26e-01	0.1276
7187	TRAF3	P27T-E	Human	Esophagus	ESCC	3.01e-10	1.85e-01	0.1055
7187	TRAF3	P28T-E	Human	Esophagus	ESCC	1.98e-15	2.83e-01	0.1149

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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
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
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

∗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:00027644	Cervix	CC	immune response-regulating signaling pathway	97/2311	468/18723	1.49e-07	7.07e-06	97
GO:00002097	Cervix	CC	protein polyubiquitination	58/2311	236/18723	1.57e-07	7.41e-06	58
GO:00310988	Cervix	CC	stress-activated protein kinase signaling cascade	58/2311	247/18723	8.02e-07	2.89e-05	58
GO:00514038	Cervix	CC	stress-activated MAPK cascade	55/2311	239/18723	2.96e-06	8.31e-05	55
GO:00510904	Cervix	CC	regulation of DNA-binding transcription factor activity	87/2311	440/18723	4.85e-06	1.22e-04	87
GO:00703027	Cervix	CC	regulation of stress-activated protein kinase signaling cascade	46/2311	195/18723	9.35e-06	2.11e-04	46
GO:00346129	Cervix	CC	response to tumor necrosis factor	55/2311	253/18723	1.75e-05	3.32e-04	55
GO:00713569	Cervix	CC	cellular response to tumor necrosis factor	51/2311	229/18723	1.75e-05	3.32e-04	51
GO:00028315	Cervix	CC	regulation of response to biotic stimulus	67/2311	327/18723	1.79e-05	3.36e-04	67
GO:00096158	Cervix	CC	response to virus	73/2311	367/18723	2.22e-05	3.95e-04	73
GO:00434104	Cervix	CC	positive regulation of MAPK cascade	90/2311	480/18723	2.92e-05	4.83e-04	90
GO:00328727	Cervix	CC	regulation of stress-activated MAPK cascade	44/2311	192/18723	3.09e-05	5.10e-04	44
GO:00431228	Cervix	CC	regulation of I-kappaB kinase/NF-kappaB signaling	53/2311	249/18723	4.50e-05	6.87e-04	53
GO:00022212	Cervix	CC	pattern recognition receptor signaling pathway	39/2311	172/18723	1.08e-04	1.38e-03	39
GO:00072497	Cervix	CC	I-kappaB kinase/NF-kappaB signaling	56/2311	281/18723	1.81e-04	2.12e-03	56
GO:00192213	Cervix	CC	cytokine-mediated signaling pathway	84/2311	472/18723	3.25e-04	3.44e-03	84
GO:00072545	Cervix	CC	JNK cascade	35/2311	167/18723	1.10e-03	9.09e-03	35
GO:00332097	Cervix	CC	tumor necrosis factor-mediated signaling pathway	23/2311	99/18723	1.86e-03	1.38e-02	23
GO:00463285	Cervix	CC	regulation of JNK cascade	28/2311	133/18723	3.06e-03	2.01e-02	28
GO:00703043	Cervix	CC	positive regulation of stress-activated protein kinase signaling cascade	27/2311	128/18723	3.49e-03	2.26e-02	27

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0517120	Cervix	CC	Coronavirus disease - COVID-19	111/1267	232/8465	1.82e-33	5.90e-31	3.49e-31	111
hsa0541720	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa0516720	Cervix	CC	Kaposi sarcoma-associated herpesvirus infection	60/1267	194/8465	9.74e-09	1.58e-07	9.33e-08	60
hsa0516920	Cervix	CC	Epstein-Barr virus infection	57/1267	202/8465	7.30e-07	7.39e-06	4.37e-06	57
hsa0465718	Cervix	CC	IL-17 signaling pathway	31/1267	94/8465	8.71e-06	7.43e-05	4.39e-05	31
hsa052226	Cervix	CC	Small cell lung cancer	29/1267	92/8465	4.38e-05	3.09e-04	1.83e-04	29
hsa051657	Cervix	CC	Human papillomavirus infection	74/1267	331/8465	1.70e-04	1.02e-03	6.03e-04	74
hsa0516414	Cervix	CC	Influenza A	43/1267	171/8465	3.03e-04	1.64e-03	9.68e-04	43
hsa046686	Cervix	CC	TNF signaling pathway	28/1267	114/8465	4.60e-03	1.62e-02	9.59e-03	28
hsa046213	Cervix	CC	NOD-like receptor signaling pathway	41/1267	186/8465	5.90e-03	1.95e-02	1.15e-02	41
hsa05171110	Cervix	CC	Coronavirus disease - COVID-19	111/1267	232/8465	1.82e-33	5.90e-31	3.49e-31	111
hsa05417110	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa05167110	Cervix	CC	Kaposi sarcoma-associated herpesvirus infection	60/1267	194/8465	9.74e-09	1.58e-07	9.33e-08	60
hsa05169110	Cervix	CC	Epstein-Barr virus infection	57/1267	202/8465	7.30e-07	7.39e-06	4.37e-06	57
hsa0465719	Cervix	CC	IL-17 signaling pathway	31/1267	94/8465	8.71e-06	7.43e-05	4.39e-05	31
hsa0522213	Cervix	CC	Small cell lung cancer	29/1267	92/8465	4.38e-05	3.09e-04	1.83e-04	29
hsa0516512	Cervix	CC	Human papillomavirus infection	74/1267	331/8465	1.70e-04	1.02e-03	6.03e-04	74
hsa0516415	Cervix	CC	Influenza A	43/1267	171/8465	3.03e-04	1.64e-03	9.68e-04	43
hsa0466813	Cervix	CC	TNF signaling pathway	28/1267	114/8465	4.60e-03	1.62e-02	9.59e-03	28
hsa0462112	Cervix	CC	NOD-like receptor signaling pathway	41/1267	186/8465	5.90e-03	1.95e-02	1.15e-02	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

TRAF3

SNV

Missense_Mutation

novel

c.1552A>G

p.Ser518Gly

p.S518G

Q13114

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A0FK-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

TRAF3

SNV

Missense_Mutation

novel

c.1591N>A

p.Ala531Thr

p.A531T

Q13114

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AR-A24T-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

TRAF3

SNV

Missense_Mutation

c.599N>C

p.Val200Ala

p.V200A

Q13114

protein_coding

tolerated(0.6)

benign(0.079)

TCGA-C8-A26Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TRAF3

SNV

Missense_Mutation

novel

c.1624N>T

p.Val542Phe

p.V542F

Q13114

protein_coding

deleterious(0)

probably_damaging(0.966)

TCGA-E9-A54X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TRAF3

insertion

Frame_Shift_Ins

novel

c.1553_1554insATTCTGCACTGTC

p.Ser518ArgfsTer37

p.S518Rfs*37

Q13114

protein_coding

TCGA-AN-A0FK-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

TRAF3

insertion

Nonsense_Mutation

novel

c.194_195insTATTTGATCATGTTTTGTTCCCAACACATATTAAAGTTGG

p.Gln65HisfsTer3

p.Q65Hfs*3

Q13114

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

TRAF3

insertion

Nonsense_Mutation

novel

c.1541_1542insTGGGCCCCGGGCGAGTGCTGGGGCGGGGTCCGTGGGATGAGGG

p.Asp515GlyfsTer13

p.D515Gfs*13

Q13114

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

TRAF3

deletion

Frame_Shift_Del

c.1520_1523delNNNN

p.His507ArgfsTer21

p.H507Rfs*21

Q13114

protein_coding

TCGA-AR-A1AI-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

TRAF3

SNV

Missense_Mutation

c.26N>T

p.Ser9Phe

p.S9F

Q13114

protein_coding

deleterious_low_confidence(0.02)

benign(0.037)

TCGA-C5-A1MK-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

carboplatin

TRAF3

SNV

Missense_Mutation

novel

c.1234G>A

p.Ala412Thr

p.A412T

Q13114

protein_coding

tolerated(0.06)

benign(0.183)

TCGA-C5-A7X5-01

Cervix

cervical & endocervical cancer

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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