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: TNFRSF10B

Gene summary for TNFRSF10B

Gene summary.

Gene information	Species	Human
	Gene symbol	TNFRSF10B
	Gene ID	8795
	Gene name	TNF receptor superfamily member 10b
	Gene Alias	CD262
	Cytomap	8p21.3
	Gene Type	protein-coding
	GO ID	GO:0001932
	UniProtAcc	O14763

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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
8795	TNFRSF10B	CCI_1	Human	Cervix	CC	2.91e-02	5.41e-01	0.528
8795	TNFRSF10B	CCI_3	Human	Cervix	CC	5.63e-08	5.28e-01	0.516
8795	TNFRSF10B	sample3	Human	Cervix	CC	7.34e-03	1.14e-01	0.1387
8795	TNFRSF10B	AEH-subject1	Human	Endometrium	AEH	5.35e-23	6.15e-01	-0.3059
8795	TNFRSF10B	AEH-subject2	Human	Endometrium	AEH	8.58e-07	3.82e-01	-0.2525
8795	TNFRSF10B	AEH-subject3	Human	Endometrium	AEH	5.23e-07	3.93e-01	-0.2576
8795	TNFRSF10B	AEH-subject4	Human	Endometrium	AEH	7.29e-08	4.71e-01	-0.2657
8795	TNFRSF10B	AEH-subject5	Human	Endometrium	AEH	3.66e-14	5.29e-01	-0.2953
8795	TNFRSF10B	EEC-subject1	Human	Endometrium	EEC	4.63e-23	7.13e-01	-0.2682
8795	TNFRSF10B	EEC-subject2	Human	Endometrium	EEC	8.83e-07	4.14e-01	-0.2607
8795	TNFRSF10B	EEC-subject3	Human	Endometrium	EEC	5.57e-04	3.70e-01	-0.2525
8795	TNFRSF10B	EEC-subject4	Human	Endometrium	EEC	5.84e-15	5.59e-01	-0.2571
8795	TNFRSF10B	EEC-subject5	Human	Endometrium	EEC	6.56e-07	3.87e-01	-0.249
8795	TNFRSF10B	GSM5276934	Human	Endometrium	EEC	2.46e-04	3.14e-01	-0.0913
8795	TNFRSF10B	GSM5276937	Human	Endometrium	EEC	2.58e-09	4.12e-01	-0.0897
8795	TNFRSF10B	GSM6177620_NYU_UCEC1_lib1_lib1	Human	Endometrium	EEC	2.64e-04	1.45e-01	-0.1869
8795	TNFRSF10B	GSM6177620_NYU_UCEC1_lib3_lib3	Human	Endometrium	EEC	4.75e-04	1.05e-01	-0.1883
8795	TNFRSF10B	GSM6177621_NYU_UCEC2_lib1_lib1	Human	Endometrium	EEC	1.93e-05	2.46e-01	-0.1934
8795	TNFRSF10B	GSM6177622_NYU_UCEC3_lib1_lib1	Human	Endometrium	EEC	8.94e-03	-2.65e-02	-0.1917
8795	TNFRSF10B	GSM6177622_NYU_UCEC3_lib2_lib2	Human	Endometrium	EEC	2.39e-03	4.07e-02	-0.1916

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
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:009719310	Cervix	CC	intrinsic apoptotic signaling pathway	85/2311	288/18723	4.56e-15	6.46e-12	85
GO:007149610	Cervix	CC	cellular response to external stimulus	78/2311	320/18723	1.82e-09	1.98e-07	78
GO:003367410	Cervix	CC	positive regulation of kinase activity	101/2311	467/18723	8.66e-09	7.22e-07	101
GO:00458608	Cervix	CC	positive regulation of protein kinase activity	85/2311	386/18723	5.61e-08	3.29e-06	85
GO:009719110	Cervix	CC	extrinsic apoptotic signaling pathway	52/2311	219/18723	2.06e-06	6.34e-05	52
GO:003497610	Cervix	CC	response to endoplasmic reticulum stress	57/2311	256/18723	5.81e-06	1.42e-04	57
GO:00712148	Cervix	CC	cellular response to abiotic stimulus	69/2311	331/18723	7.36e-06	1.73e-04	69
GO:01040048	Cervix	CC	cellular response to environmental stimulus	69/2311	331/18723	7.36e-06	1.73e-04	69
GO:00700599	Cervix	CC	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	21/2311	63/18723	1.18e-05	2.51e-04	21
GO:00096127	Cervix	CC	response to mechanical stimulus	48/2311	216/18723	3.23e-05	5.29e-04	48
GO:00431228	Cervix	CC	regulation of I-kappaB kinase/NF-kappaB signaling	53/2311	249/18723	4.50e-05	6.87e-04	53
GO:00712602	Cervix	CC	cellular response to mechanical stimulus	23/2311	81/18723	8.34e-05	1.12e-03	23
GO:00072497	Cervix	CC	I-kappaB kinase/NF-kappaB signaling	56/2311	281/18723	1.81e-04	2.12e-03	56
GO:00431237	Cervix	CC	positive regulation of I-kappaB kinase/NF-kappaB signaling	37/2311	186/18723	2.15e-03	1.55e-02	37
GO:00086259	Cervix	CC	extrinsic apoptotic signaling pathway via death domain receptors	19/2311	82/18723	4.57e-03	2.77e-02	19
GO:009719316	Endometrium	AEH	intrinsic apoptotic signaling pathway	75/2100	288/18723	1.46e-12	2.83e-10	75
GO:003497616	Endometrium	AEH	response to endoplasmic reticulum stress	62/2100	256/18723	2.88e-09	2.13e-07	62
GO:009719116	Endometrium	AEH	extrinsic apoptotic signaling pathway	49/2100	219/18723	1.58e-06	4.94e-05	49
GO:00431229	Endometrium	AEH	regulation of I-kappaB kinase/NF-kappaB signaling	52/2100	249/18723	6.58e-06	1.59e-04	52
GO:00431238	Endometrium	AEH	positive regulation of I-kappaB kinase/NF-kappaB signaling	41/2100	186/18723	1.59e-05	3.32e-04	41

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513020	Cervix	CC	Pathogenic Escherichia coli infection	63/1267	197/8465	9.28e-10	2.00e-08	1.19e-08	63
hsa0513220	Cervix	CC	Salmonella infection	74/1267	249/8465	1.33e-09	2.54e-08	1.50e-08	74
hsa0541720	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa0516414	Cervix	CC	Influenza A	43/1267	171/8465	3.03e-04	1.64e-03	9.68e-04	43
hsa042109	Cervix	CC	Apoptosis	36/1267	136/8465	3.21e-04	1.68e-03	9.91e-04	36
hsa05130110	Cervix	CC	Pathogenic Escherichia coli infection	63/1267	197/8465	9.28e-10	2.00e-08	1.19e-08	63
hsa05132110	Cervix	CC	Salmonella infection	74/1267	249/8465	1.33e-09	2.54e-08	1.50e-08	74
hsa05417110	Cervix	CC	Lipid and atherosclerosis	65/1267	215/8465	6.47e-09	1.10e-07	6.52e-08	65
hsa0516415	Cervix	CC	Influenza A	43/1267	171/8465	3.03e-04	1.64e-03	9.68e-04	43
hsa0421014	Cervix	CC	Apoptosis	36/1267	136/8465	3.21e-04	1.68e-03	9.91e-04	36
hsa0513226	Endometrium	AEH	Salmonella infection	71/1197	249/8465	1.69e-09	3.44e-08	2.52e-08	71
hsa0513026	Endometrium	AEH	Pathogenic Escherichia coli infection	50/1197	197/8465	1.72e-05	1.86e-04	1.36e-04	50
hsa0541726	Endometrium	AEH	Lipid and atherosclerosis	47/1197	215/8465	1.24e-03	7.62e-03	5.58e-03	47
hsa0421010	Endometrium	AEH	Apoptosis	30/1197	136/8465	7.72e-03	4.05e-02	2.96e-02	30
hsa05132112	Endometrium	AEH	Salmonella infection	71/1197	249/8465	1.69e-09	3.44e-08	2.52e-08	71
hsa05130112	Endometrium	AEH	Pathogenic Escherichia coli infection	50/1197	197/8465	1.72e-05	1.86e-04	1.36e-04	50
hsa05417111	Endometrium	AEH	Lipid and atherosclerosis	47/1197	215/8465	1.24e-03	7.62e-03	5.58e-03	47
hsa0421015	Endometrium	AEH	Apoptosis	30/1197	136/8465	7.72e-03	4.05e-02	2.96e-02	30
hsa0513227	Endometrium	EEC	Salmonella infection	71/1237	249/8465	7.11e-09	1.30e-07	9.69e-08	71
hsa0513027	Endometrium	EEC	Pathogenic Escherichia coli infection	51/1237	197/8465	1.98e-05	2.28e-04	1.70e-04	51

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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

TNFRSF10B

SNV

Missense_Mutation

novel

c.1284N>A

p.Phe428Leu

p.F428L

O14763

protein_coding

deleterious(0.01)

benign(0.125)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TNFRSF10B

SNV

Missense_Mutation

novel

c.1030G>T

p.Asp344Tyr

p.D344Y

O14763

protein_coding

tolerated(0.12)

benign(0.001)

TCGA-AR-A2LR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TNFRSF10B

insertion

Frame_Shift_Ins

novel

c.858_859insACTAGCCTGGCCAACATGGTGAAACCCTGTCT

p.Gln287ThrfsTer63

p.Q287Tfs*63

O14763

protein_coding

TCGA-A7-A0CG-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TNFRSF10B

insertion

In_Frame_Ins

novel

c.955_956insTCGTCCCGAGATCTGGGCAGCATTGCTCGGTCTTTG

p.Arg319delinsIleValProArgSerGlyGlnHisCysSerValPheGly

p.R319delinsIVPRSGQHCSVFG

O14763

protein_coding

TCGA-A8-A08H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TNFRSF10B

SNV

Missense_Mutation

rs748928192

c.826N>A

p.Val276Met

p.V276M

O14763

protein_coding

tolerated(0.26)

benign(0.006)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TNFRSF10B

SNV

Missense_Mutation

novel

c.187N>T

p.Pro63Ser

p.P63S

O14763

protein_coding

tolerated(0.29)

benign(0.264)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TNFRSF10B

SNV

Missense_Mutation

c.864N>C

p.Glu288Asp

p.E288D

O14763

protein_coding

tolerated(0.22)

possibly_damaging(0.76)

TCGA-FU-A3HZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TNFRSF10B

SNV

Missense_Mutation

rs529765232

c.344N>A

p.Arg115His

p.R115H

O14763

protein_coding

tolerated(0.16)

possibly_damaging(0.87)

TCGA-AA-3949-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

TNFRSF10B

SNV

Missense_Mutation

c.791G>A

p.Arg264Gln

p.R264Q

O14763

protein_coding

tolerated(0.6)

benign(0.003)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

TNFRSF10B

SNV

Missense_Mutation

c.1189N>A

p.Ala397Thr

p.A397T

O14763

protein_coding

tolerated(0.06)

probably_damaging(0.996)

TCGA-CK-4951-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

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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
8795	TNFRSF10B	DRUGGABLE GENOME, CELL SURFACE	agonist	CHEMBL2107846	DULANERMIN
8795	TNFRSF10B	DRUGGABLE GENOME, CELL SURFACE	antibody	APOMAB	APOMAB
8795	TNFRSF10B	DRUGGABLE GENOME, CELL SURFACE		LUTEOLIN	LUTEOLIN	21265555
8795	TNFRSF10B	DRUGGABLE GENOME, CELL SURFACE		HGS-TR2J
8795	TNFRSF10B	DRUGGABLE GENOME, CELL SURFACE		Conatumumab	CONATUMUMAB
8795	TNFRSF10B	DRUGGABLE GENOME, CELL SURFACE	antibody	318164853	TIGATUZUMAB
8795	TNFRSF10B	DRUGGABLE GENOME, CELL SURFACE	antibody	DULANERMIN	DULANERMIN
8795	TNFRSF10B	DRUGGABLE GENOME, CELL SURFACE		Anti-DR5 cells
8795	TNFRSF10B	DRUGGABLE GENOME, CELL SURFACE	antibody	DULANERMIN	DULANERMIN
8795	TNFRSF10B	DRUGGABLE GENOME, CELL SURFACE		LEXATUMUMAB	LEXATUMUMAB

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