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: CD70

Gene summary for CD70

Gene summary.

Gene information	Species	Human
	Gene symbol	CD70
	Gene ID	970
	Gene name	CD70 molecule
	Gene Alias	CD27-L
	Cytomap	19p13.3
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	A0A0U5JA32

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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
970	CD70	LZE8T	Human	Esophagus	ESCC	4.41e-02	1.10e-01	0.067
970	CD70	LZE6T	Human	Esophagus	ESCC	1.16e-11	5.79e-01	0.0845
970	CD70	P2T-E	Human	Esophagus	ESCC	2.78e-38	7.69e-01	0.1177
970	CD70	P5T-E	Human	Esophagus	ESCC	4.31e-06	1.37e-01	0.1327
970	CD70	P16T-E	Human	Esophagus	ESCC	3.97e-04	1.18e-01	0.1153
970	CD70	P21T-E	Human	Esophagus	ESCC	3.75e-03	1.54e-01	0.1617
970	CD70	P24T-E	Human	Esophagus	ESCC	4.30e-10	2.58e-01	0.1287
970	CD70	P37T-E	Human	Esophagus	ESCC	1.53e-03	1.49e-01	0.1371
970	CD70	P38T-E	Human	Esophagus	ESCC	6.27e-24	9.03e-01	0.127
970	CD70	P52T-E	Human	Esophagus	ESCC	3.50e-02	1.02e-01	0.1555
970	CD70	P56T-E	Human	Esophagus	ESCC	1.10e-03	4.55e-01	0.1613
970	CD70	P62T-E	Human	Esophagus	ESCC	4.45e-39	9.00e-01	0.1302
970	CD70	P74T-E	Human	Esophagus	ESCC	2.11e-10	3.75e-01	0.1479
970	CD70	P75T-E	Human	Esophagus	ESCC	3.52e-19	6.32e-01	0.1125
970	CD70	P76T-E	Human	Esophagus	ESCC	6.62e-20	6.89e-01	0.1207
970	CD70	P79T-E	Human	Esophagus	ESCC	2.06e-08	2.29e-01	0.1154
970	CD70	P80T-E	Human	Esophagus	ESCC	2.37e-09	3.80e-01	0.155
970	CD70	P107T-E	Human	Esophagus	ESCC	2.29e-02	2.73e-01	0.171
970	CD70	P130T-E	Human	Esophagus	ESCC	1.47e-75	1.79e+00	0.1676
970	CD70	HCC1	Human	Liver	HCC	1.33e-15	9.42e-01	0.5336

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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
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:0097191111	Esophagus	ESCC	extrinsic apoptotic signaling pathway	159/8552	219/18723	4.12e-16	2.94e-14	159
GO:004578527	Esophagus	ESCC	positive regulation of cell adhesion	255/8552	437/18723	5.07e-08	9.11e-07	255
GO:003320914	Esophagus	ESCC	tumor necrosis factor-mediated signaling pathway	67/8552	99/18723	7.87e-06	7.72e-05	67
GO:003461220	Esophagus	ESCC	response to tumor necrosis factor	149/8552	253/18723	1.47e-05	1.33e-04	149
GO:007135620	Esophagus	ESCC	cellular response to tumor necrosis factor	132/8552	229/18723	1.69e-04	1.11e-03	132
GO:002240720	Esophagus	ESCC	regulation of cell-cell adhesion	239/8552	448/18723	5.88e-04	3.19e-03	239
GO:004211018	Esophagus	ESCC	T cell activation	256/8552	487/18723	1.18e-03	5.87e-03	256
GO:002240919	Esophagus	ESCC	positive regulation of cell-cell adhesion	155/8552	284/18723	1.50e-03	7.06e-03	155
GO:005087015	Esophagus	ESCC	positive regulation of T cell activation	117/8552	216/18723	7.23e-03	2.62e-02	117
GO:190303916	Esophagus	ESCC	positive regulation of leukocyte cell-cell adhesion	128/8552	239/18723	8.40e-03	2.96e-02	128
GO:000715918	Esophagus	ESCC	leukocyte cell-cell adhesion	192/8552	371/18723	1.03e-02	3.51e-02	192
GO:190303717	Esophagus	ESCC	regulation of leukocyte cell-cell adhesion	174/8552	336/18723	1.36e-02	4.43e-02	174
GO:009719122	Liver	HCC	extrinsic apoptotic signaling pathway	143/7958	219/18723	6.99e-12	2.97e-10	143
GO:003461211	Liver	HCC	response to tumor necrosis factor	132/7958	253/18723	1.14e-03	6.48e-03	132
GO:004578512	Liver	HCC	positive regulation of cell adhesion	215/7958	437/18723	2.53e-03	1.22e-02	215
GO:007135611	Liver	HCC	cellular response to tumor necrosis factor	115/7958	229/18723	1.08e-02	3.99e-02	115
GO:009719120	Oral cavity	OSCC	extrinsic apoptotic signaling pathway	142/7305	219/18723	7.34e-15	4.55e-13	142
GO:003461218	Oral cavity	OSCC	response to tumor necrosis factor	143/7305	253/18723	1.09e-08	2.23e-07	143
GO:004578520	Oral cavity	OSCC	positive regulation of cell adhesion	225/7305	437/18723	6.06e-08	1.09e-06	225
GO:007135618	Oral cavity	OSCC	cellular response to tumor necrosis factor	128/7305	229/18723	1.49e-07	2.49e-06	128

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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
CD70	CD27	CD70_CD27	CD70	Breast	ADJ
CD70	CD27	CD70_CD27	CD70	Cervix	ADJ
CD70	CD27	CD70_CD27	CD70	Endometrium	ADJ
CD70	CD27	CD70_CD27	CD70	Endometrium	AEH
CD70	CD27	CD70_CD27	CD70	Endometrium	EEC
CD70	CD27	CD70_CD27	CD70	Esophagus	ESCC
CD70	CD27	CD70_CD27	CD70	GC	GC
CD70	CD27	CD70_CD27	CD70	HNSCC	OSCC
CD70	CD27	CD70_CD27	CD70	HNSCC	Precancer
CD70	CD27	CD70_CD27	CD70	Liver	Precancer
CD70	CD27	CD70_CD27	CD70	Lung	AIS
CD70	CD27	CD70_CD27	CD70	Lung	MIAC
CD70	CD27	CD70_CD27	CD70	Lung	Precancer
CD70	CD27	CD70_CD27	CD70	Prostate	BPH
CD70	CD27	CD70_CD27	CD70	Skin	ADJ
CD70	CD27	CD70_CD27	CD70	Skin	SCCIS
CD70	CD27	CD70_CD27	CD70	THCA	Cancer

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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

CD70

SNV

Missense_Mutation

c.377N>A

p.Thr126Asn

p.T126N

P32970

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.462)

TCGA-A2-A04R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxol

CD70

SNV

Missense_Mutation

rs548095306

c.388N>A

p.Val130Met

p.V130M

P32970

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.954)

TCGA-AA-3845-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

CD70

SNV

Missense_Mutation

c.32N>A

p.Arg11Gln

p.R11Q

P32970

protein_coding

tolerated_low_confidence(0.49)

benign(0.441)

TCGA-AA-3848-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

CD70

SNV

Missense_Mutation

novel

c.62N>T

p.Ala21Val

p.A21V

P32970

protein_coding

tolerated_low_confidence(0.67)

benign(0.006)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CD70

SNV

Missense_Mutation

novel

c.275A>G

p.Asp92Gly

p.D92G

P32970

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.816)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CD70

SNV

Missense_Mutation

rs141989071

c.290N>A

p.Arg97His

p.R97H

P32970

protein_coding

tolerated_low_confidence(0.06)

benign(0.068)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

CD70

SNV

Missense_Mutation

novel

c.365N>T

p.Arg122Met

p.R122M

P32970

protein_coding

tolerated_low_confidence(0.13)

possibly_damaging(0.572)

TCGA-AP-A1DO-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CD70

SNV

Missense_Mutation

novel

c.416N>T

p.Ser139Ile

p.S139I

P32970

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.684)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CD70

SNV

Missense_Mutation

novel

c.401C>T

p.Ser134Phe

p.S134F

P32970

protein_coding

deleterious_low_confidence(0.02)

benign(0.063)

TCGA-B5-A3FC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

CD70

SNV

Missense_Mutation

rs750046562

c.289C>T

p.Arg97Cys

p.R97C

P32970

protein_coding

deleterious_low_confidence(0.03)

probably_damaging(0.958)

TCGA-D1-A176-01

Endometrium

uterine corpus endometrioid carcinoma

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
970	CD70	CLINICALLY ACTIONABLE, DRUGGABLE GENOME		AMG 172
970	CD70	CLINICALLY ACTIONABLE, DRUGGABLE GENOME		SGN-70
970	CD70	CLINICALLY ACTIONABLE, DRUGGABLE GENOME		4SCAR19 and 4SCAR70
970	CD70	CLINICALLY ACTIONABLE, DRUGGABLE GENOME		MDX-1411	MDX-1411
970	CD70	CLINICALLY ACTIONABLE, DRUGGABLE GENOME		MDX-1411	MDX-1411
970	CD70	CLINICALLY ACTIONABLE, DRUGGABLE GENOME		MDX-1203
970	CD70	CLINICALLY ACTIONABLE, DRUGGABLE GENOME		SGN-CD70A
970	CD70	CLINICALLY ACTIONABLE, DRUGGABLE GENOME		SGN-75	VORSETUZUMAB MAFODOTIN
970	CD70	CLINICALLY ACTIONABLE, DRUGGABLE GENOME		MDX-1203
970	CD70	CLINICALLY ACTIONABLE, DRUGGABLE GENOME		Anti-hCD70 CAR transduced PBL

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