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: ARFIP2

Gene summary for ARFIP2

Gene summary.

Gene information	Species	Human
	Gene symbol	ARFIP2
	Gene ID	23647
	Gene name	ADP ribosylation factor interacting protein 2
	Gene Alias	POR1
	Cytomap	11p15.4
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	A0A087X1E4

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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
23647	ARFIP2	LZE4T	Human	Esophagus	ESCC	8.89e-04	1.24e-01	0.0811
23647	ARFIP2	LZE5T	Human	Esophagus	ESCC	1.27e-03	3.03e-01	0.0514
23647	ARFIP2	LZE7T	Human	Esophagus	ESCC	4.42e-03	3.54e-01	0.0667
23647	ARFIP2	LZE8T	Human	Esophagus	ESCC	5.78e-04	2.00e-01	0.067
23647	ARFIP2	LZE20T	Human	Esophagus	ESCC	7.89e-05	1.03e-01	0.0662
23647	ARFIP2	LZE24T	Human	Esophagus	ESCC	2.49e-17	5.22e-01	0.0596
23647	ARFIP2	LZE21T	Human	Esophagus	ESCC	4.37e-03	1.39e-01	0.0655
23647	ARFIP2	P1T-E	Human	Esophagus	ESCC	9.51e-04	3.73e-01	0.0875
23647	ARFIP2	P2T-E	Human	Esophagus	ESCC	5.18e-19	3.82e-01	0.1177
23647	ARFIP2	P4T-E	Human	Esophagus	ESCC	1.33e-15	2.20e-01	0.1323
23647	ARFIP2	P5T-E	Human	Esophagus	ESCC	4.59e-17	1.18e-01	0.1327
23647	ARFIP2	P8T-E	Human	Esophagus	ESCC	1.57e-23	2.22e-01	0.0889
23647	ARFIP2	P9T-E	Human	Esophagus	ESCC	9.23e-12	3.47e-01	0.1131
23647	ARFIP2	P10T-E	Human	Esophagus	ESCC	3.15e-23	4.79e-01	0.116
23647	ARFIP2	P11T-E	Human	Esophagus	ESCC	4.62e-07	5.68e-01	0.1426
23647	ARFIP2	P12T-E	Human	Esophagus	ESCC	4.54e-21	2.73e-01	0.1122
23647	ARFIP2	P15T-E	Human	Esophagus	ESCC	2.06e-13	3.16e-01	0.1149
23647	ARFIP2	P16T-E	Human	Esophagus	ESCC	3.47e-11	2.81e-01	0.1153
23647	ARFIP2	P17T-E	Human	Esophagus	ESCC	2.44e-09	5.77e-01	0.1278
23647	ARFIP2	P20T-E	Human	Esophagus	ESCC	5.68e-09	3.86e-01	0.1124

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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
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:0043254111	Esophagus	ESCC	regulation of protein-containing complex assembly	278/8552	428/18723	3.81e-16	2.77e-14	278
GO:0031334111	Esophagus	ESCC	positive regulation of protein-containing complex assembly	166/8552	237/18723	2.06e-14	1.07e-12	166
GO:1902905111	Esophagus	ESCC	positive regulation of supramolecular fiber organization	142/8552	209/18723	5.51e-11	1.76e-09	142
GO:1902903111	Esophagus	ESCC	regulation of supramolecular fiber organization	237/8552	383/18723	9.06e-11	2.75e-09	237
GO:005149520	Esophagus	ESCC	positive regulation of cytoskeleton organization	147/8552	226/18723	2.93e-09	6.38e-08	147
GO:0051258111	Esophagus	ESCC	protein polymerization	183/8552	297/18723	1.94e-08	3.75e-07	183
GO:000701527	Esophagus	ESCC	actin filament organization	259/8552	442/18723	2.37e-08	4.50e-07	259
GO:0032273111	Esophagus	ESCC	positive regulation of protein polymerization	95/8552	138/18723	2.97e-08	5.57e-07	95
GO:003253520	Esophagus	ESCC	regulation of cellular component size	227/8552	383/18723	4.77e-08	8.60e-07	227
GO:0032970111	Esophagus	ESCC	regulation of actin filament-based process	231/8552	397/18723	2.91e-07	4.20e-06	231
GO:0032956111	Esophagus	ESCC	regulation of actin cytoskeleton organization	210/8552	358/18723	4.40e-07	6.00e-06	210
GO:0032271111	Esophagus	ESCC	regulation of protein polymerization	143/8552	233/18723	9.21e-07	1.17e-05	143
GO:011005327	Esophagus	ESCC	regulation of actin filament organization	166/8552	278/18723	1.54e-06	1.85e-05	166
GO:003083819	Esophagus	ESCC	positive regulation of actin filament polymerization	66/8552	99/18723	1.96e-05	1.72e-04	66
GO:000815420	Esophagus	ESCC	actin polymerization or depolymerization	130/8552	218/18723	2.19e-05	1.88e-04	130
GO:0030041110	Esophagus	ESCC	actin filament polymerization	114/8552	191/18723	6.46e-05	4.92e-04	114
GO:000806419	Esophagus	ESCC	regulation of actin polymerization or depolymerization	112/8552	188/18723	8.31e-05	6.06e-04	112
GO:003083218	Esophagus	ESCC	regulation of actin filament length	112/8552	189/18723	1.13e-04	7.85e-04	112
GO:003083320	Esophagus	ESCC	regulation of actin filament polymerization	103/8552	172/18723	1.19e-04	8.15e-04	103
GO:00315299	Esophagus	ESCC	ruffle organization	39/8552	56/18723	2.44e-04	1.51e-03	39

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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

ARFIP2

SNV

Missense_Mutation

novel

c.373N>C

p.Lys125Gln

p.K125Q

protein_coding

deleterious(0.02)

probably_damaging(0.995)

TCGA-3C-AALJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

ARFIP2

SNV

Missense_Mutation

novel

c.472N>A

p.Glu158Lys

p.E158K

protein_coding

deleterious(0.01)

probably_damaging(0.984)

TCGA-AR-A2LE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

ARFIP2

insertion

Frame_Shift_Ins

novel

c.425_426insTT

p.Gln142HisfsTer19

p.Q142Hfs*19

protein_coding

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

ARFIP2

insertion

Frame_Shift_Ins

novel

c.424_425insTTTTAATAAATAAAAATTTAGAAAAG

p.Gln142LeufsTer27

p.Q142Lfs*27

protein_coding

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

ARFIP2

insertion

Nonsense_Mutation

novel

c.1047_1048insTCTTCTGGGCTTTGATCA

p.Leu349_Glu350insSerSerGlyLeuTerSer

p.L349_E350insSSGL*S

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

ARFIP2

SNV

Missense_Mutation

rs773493084

c.1081C>T

p.Arg361Trp

p.R361W

protein_coding

deleterious(0)

possibly_damaging(0.847)

TCGA-EK-A2PL-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

ARFIP2

SNV

Missense_Mutation

c.502N>C

p.Glu168Gln

p.E168Q

protein_coding

deleterious(0)

benign(0.234)

TCGA-EK-A3GK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

ARFIP2

SNV

Missense_Mutation

rs766340094

c.221G>A

p.Arg74Lys

p.R74K

protein_coding

tolerated(0.95)

benign(0)

TCGA-JX-A3Q0-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

ARFIP2

SNV

Missense_Mutation

c.458N>T

p.Arg153Leu

p.R153L

protein_coding

deleterious(0)

probably_damaging(0.984)

TCGA-AA-3966-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

ARFIP2

SNV

Missense_Mutation

novel

c.358N>A

p.Gly120Ser

p.G120S

protein_coding

tolerated(0.43)

probably_damaging(0.999)

TCGA-AJ-A23O-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

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