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: XPR1

Gene summary for XPR1

Gene summary.

Gene information	Species	Human
	Gene symbol	XPR1
	Gene ID	9213
	Gene name	xenotropic and polytropic retrovirus receptor 1
	Gene Alias	IBGC6
	Cytomap	1q25.3
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	Q9UBH6

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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
9213	XPR1	Dong_P5	Human	Prostate	Tumor	2.36e-06	-2.82e-02	0.053
9213	XPR1	P1_S1_AK	Human	Skin	AK	5.03e-23	5.51e-01	-0.3399
9213	XPR1	P2_S3_AK	Human	Skin	AK	4.91e-19	4.44e-01	-0.3287
9213	XPR1	P2_S4_SCCIS	Human	Skin	SCCIS	3.61e-14	3.79e-01	-0.3043
9213	XPR1	P3_S6_AK	Human	Skin	AK	6.64e-05	2.89e-01	-0.3256
9213	XPR1	P4_S8_cSCC	Human	Skin	cSCC	1.04e-04	2.22e-01	-0.3095
9213	XPR1	P5_S10_cSCC	Human	Skin	cSCC	1.45e-49	8.77e-01	-0.299
9213	XPR1	P1_cSCC	Human	Skin	cSCC	3.74e-05	2.86e-01	0.0292
9213	XPR1	P4_cSCC	Human	Skin	cSCC	1.53e-09	2.42e-01	-0.00290000000000005
9213	XPR1	P10_cSCC	Human	Skin	cSCC	3.87e-22	5.59e-01	0.1017
9213	XPR1	male-WTA	Human	Thyroid	PTC	9.66e-44	4.17e-01	0.1037
9213	XPR1	female-WTA	Human	Thyroid	PTC	2.91e-03	3.93e-01	0.0726
9213	XPR1	PTC01	Human	Thyroid	PTC	2.75e-05	2.46e-01	0.1899
9213	XPR1	PTC04	Human	Thyroid	PTC	7.32e-17	4.70e-01	0.1927
9213	XPR1	PTC05	Human	Thyroid	PTC	1.61e-25	8.48e-01	0.2065
9213	XPR1	PTC06	Human	Thyroid	PTC	4.46e-50	1.17e+00	0.2057
9213	XPR1	PTC07	Human	Thyroid	PTC	8.60e-25	4.45e-01	0.2044
9213	XPR1	ATC13	Human	Thyroid	ATC	2.70e-13	-8.16e-03	0.34
9213	XPR1	ATC2	Human	Thyroid	ATC	1.31e-08	5.62e-01	0.34
9213	XPR1	ATC4	Human	Thyroid	ATC	2.42e-02	-5.36e-02	0.34

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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
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
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
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:001603210	Cervix	CC	viral process	109/2311	415/18723	5.40e-15	6.46e-12	109
GO:001905810	Cervix	CC	viral life cycle	87/2311	317/18723	2.20e-13	1.20e-10	87
GO:005212610	Cervix	CC	movement in host environment	52/2311	175/18723	7.03e-10	8.76e-08	52
GO:004440910	Cervix	CC	entry into host	47/2311	151/18723	8.45e-10	1.03e-07	47
GO:005170110	Cervix	CC	biological process involved in interaction with host	57/2311	203/18723	1.18e-09	1.41e-07	57
GO:007149610	Cervix	CC	cellular response to external stimulus	78/2311	320/18723	1.82e-09	1.98e-07	78
GO:004671810	Cervix	CC	viral entry into host cell	44/2311	144/18723	5.47e-09	5.03e-07	44
GO:004440310	Cervix	CC	biological process involved in symbiotic interaction	71/2311	290/18723	7.94e-09	6.98e-07	71
GO:00316689	Cervix	CC	cellular response to extracellular stimulus	59/2311	246/18723	3.03e-07	1.24e-05	59
GO:003166710	Cervix	CC	response to nutrient levels	92/2311	474/18723	5.80e-06	1.42e-04	92
GO:00092678	Cervix	CC	cellular response to starvation	39/2311	156/18723	1.04e-05	2.32e-04	39
GO:00425948	Cervix	CC	response to starvation	46/2311	197/18723	1.24e-05	2.59e-04	46
GO:00316698	Cervix	CC	cellular response to nutrient levels	49/2311	215/18723	1.32e-05	2.68e-04	49
GO:00096158	Cervix	CC	response to virus	73/2311	367/18723	2.22e-05	3.95e-04	73
GO:0016032	Colorectum	AD	viral process	168/3918	415/18723	4.67e-20	3.66e-17	168
GO:0019058	Colorectum	AD	viral life cycle	119/3918	317/18723	6.18e-12	8.23e-10	119
GO:0044403	Colorectum	AD	biological process involved in symbiotic interaction	99/3918	290/18723	1.02e-07	4.93e-06	99
GO:0051701	Colorectum	AD	biological process involved in interaction with host	73/3918	203/18723	5.08e-07	1.88e-05	73
GO:0052126	Colorectum	AD	movement in host environment	63/3918	175/18723	2.85e-06	8.11e-05	63
GO:0031667	Colorectum	AD	response to nutrient levels	138/3918	474/18723	1.22e-05	2.68e-04	138

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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

XPR1

SNV

Missense_Mutation

c.101N>G

p.Asp34Gly

p.D34G

Q9UBH6

protein_coding

deleterious(0.02)

benign(0.3)

TCGA-A7-A26H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

XPR1

SNV

Missense_Mutation

c.2077G>A

p.Glu693Lys

p.E693K

Q9UBH6

protein_coding

deleterious_low_confidence(0.02)

benign(0.257)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

XPR1

SNV

Missense_Mutation

novel

c.926N>A

p.Ser309Asn

p.S309N

Q9UBH6

protein_coding

tolerated(1)

benign(0.001)

TCGA-AC-A7VC-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

XPR1

SNV

Missense_Mutation

novel

c.1376G>A

p.Arg459His

p.R459H

Q9UBH6

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

XPR1

SNV

Missense_Mutation

novel

c.1005N>A

p.Phe335Leu

p.F335L

Q9UBH6

protein_coding

tolerated(1)

benign(0)

TCGA-D8-A4Z1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

XPR1

SNV

Missense_Mutation

c.1832G>A

p.Arg611His

p.R611H

Q9UBH6

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-EW-A2FS-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

goserelin

XPR1

SNV

Missense_Mutation

rs751223491

c.1342C>T

p.Arg448Trp

p.R448W

Q9UBH6

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

XPR1

SNV

Missense_Mutation

c.817C>T

p.Arg273Trp

p.R273W

Q9UBH6

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

XPR1

SNV

Missense_Mutation

c.2077N>A

p.Glu693Lys

p.E693K

Q9UBH6

protein_coding

deleterious_low_confidence(0.02)

benign(0.257)

TCGA-EK-A3GN-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

XPR1

SNV

Missense_Mutation

c.1798N>A

p.Glu600Lys

p.E600K

Q9UBH6

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

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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