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: RBP1

Gene summary for RBP1

Gene summary.

Gene information	Species	Human
	Gene symbol	RBP1
	Gene ID	5947
	Gene name	retinol binding protein 1
	Gene Alias	CRABP-I
	Cytomap	3q23
	Gene Type	protein-coding
	GO ID	GO:0001523
	UniProtAcc	P09455

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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
5947	RBP1	GSM4909282	Human	Breast	IDC	8.89e-36	7.68e-01	-0.0288
5947	RBP1	GSM4909285	Human	Breast	IDC	1.09e-51	9.46e-01	0.21
5947	RBP1	GSM4909287	Human	Breast	IDC	6.65e-15	4.91e-01	0.2057
5947	RBP1	GSM4909289	Human	Breast	IDC	5.28e-21	1.06e+00	0.1064
5947	RBP1	GSM4909293	Human	Breast	IDC	1.41e-103	1.42e+00	0.1581
5947	RBP1	GSM4909294	Human	Breast	IDC	9.09e-06	2.73e-01	0.2022
5947	RBP1	GSM4909297	Human	Breast	IDC	1.01e-03	1.61e-01	0.1517
5947	RBP1	GSM4909298	Human	Breast	IDC	2.45e-33	6.73e-01	0.1551
5947	RBP1	GSM4909299	Human	Breast	IDC	2.66e-08	3.48e-01	0.035
5947	RBP1	GSM4909300	Human	Breast	IDC	8.33e-15	6.78e-01	0.0334
5947	RBP1	GSM4909301	Human	Breast	IDC	5.28e-11	4.13e-01	0.1577
5947	RBP1	GSM4909304	Human	Breast	IDC	1.87e-04	-1.80e-01	0.1636
5947	RBP1	GSM4909305	Human	Breast	IDC	3.87e-05	2.96e-01	0.0436
5947	RBP1	GSM4909306	Human	Breast	IDC	1.41e-10	3.71e-01	0.1564
5947	RBP1	GSM4909309	Human	Breast	IDC	6.33e-03	2.63e-01	0.0483
5947	RBP1	GSM4909311	Human	Breast	IDC	1.57e-05	-9.80e-02	0.1534
5947	RBP1	GSM4909312	Human	Breast	IDC	1.77e-06	-1.84e-01	0.1552
5947	RBP1	GSM4909313	Human	Breast	IDC	6.12e-05	3.23e-01	0.0391
5947	RBP1	GSM4909319	Human	Breast	IDC	1.77e-06	-1.86e-01	0.1563
5947	RBP1	GSM4909321	Human	Breast	IDC	9.21e-03	-1.41e-01	0.1559

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:000640220	Esophagus	HGIN	mRNA catabolic process	67/2587	232/18723	1.47e-09	1.13e-07	67
GO:003465519	Esophagus	HGIN	nucleobase-containing compound catabolic process	98/2587	407/18723	1.44e-08	8.94e-07	98
GO:004670017	Esophagus	HGIN	heterocycle catabolic process	103/2587	445/18723	5.44e-08	2.99e-06	103
GO:004427018	Esophagus	HGIN	cellular nitrogen compound catabolic process	103/2587	451/18723	1.10e-07	5.56e-06	103
GO:001943917	Esophagus	HGIN	aromatic compound catabolic process	105/2587	467/18723	1.89e-07	9.31e-06	105
GO:00068889	Esophagus	HGIN	endoplasmic reticulum to Golgi vesicle-mediated transport	40/2587	130/18723	4.67e-07	2.07e-05	40
GO:190136117	Esophagus	HGIN	organic cyclic compound catabolic process	106/2587	495/18723	1.94e-06	7.13e-05	106
GO:006101318	Esophagus	HGIN	regulation of mRNA catabolic process	43/2587	166/18723	2.48e-05	6.53e-04	43
GO:00069975	Esophagus	HGIN	nucleus organization	34/2587	133/18723	2.20e-04	4.00e-03	34
GO:000164917	Esophagus	HGIN	osteoblast differentiation	50/2587	229/18723	5.88e-04	8.30e-03	50
GO:004348818	Esophagus	HGIN	regulation of mRNA stability	37/2587	158/18723	7.53e-04	9.97e-03	37
GO:004348718	Esophagus	HGIN	regulation of RNA stability	39/2587	170/18723	8.42e-04	1.09e-02	39
GO:000150316	Esophagus	HGIN	ossification	75/2587	408/18723	5.49e-03	4.49e-02	75
GO:003447015	Esophagus	ESCC	ncRNA processing	300/8552	395/18723	3.09e-35	3.26e-32	300
GO:003466012	Esophagus	ESCC	ncRNA metabolic process	346/8552	485/18723	4.35e-31	2.51e-28	346
GO:004819318	Esophagus	ESCC	Golgi vesicle transport	231/8552	296/18723	1.82e-30	9.63e-28	231
GO:1903311110	Esophagus	ESCC	regulation of mRNA metabolic process	210/8552	288/18723	3.25e-21	5.56e-19	210
GO:0006401110	Esophagus	ESCC	RNA catabolic process	204/8552	278/18723	3.39e-21	5.66e-19	204
GO:0034655110	Esophagus	ESCC	nucleobase-containing compound catabolic process	272/8552	407/18723	2.92e-18	2.90e-16	272
GO:0006402110	Esophagus	ESCC	mRNA catabolic process	170/8552	232/18723	8.70e-18	8.00e-16	170

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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

RBP1

SNV

Missense_Mutation

novel

c.88N>T

p.Arg30Trp

p.R30W

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.855)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RBP1

SNV

Missense_Mutation

c.10N>T

p.Pro4Ser

p.P4S

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.651)

TCGA-BH-A18P-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

RBP1

SNV

Missense_Mutation

c.196N>A

p.Asp66Asn

p.D66N

protein_coding

tolerated(0.4)

benign(0.006)

TCGA-C8-A26W-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

RBP1

SNV

Missense_Mutation

c.575T>C

p.Val192Ala

p.V192A

protein_coding

deleterious(0.03)

probably_damaging(0.989)

TCGA-D8-A142-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyclophosphamid

RBP1

SNV

Missense_Mutation

novel

c.428G>A

p.Arg143His

p.R143H

protein_coding

deleterious(0)

probably_damaging(0.972)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RBP1

SNV

Missense_Mutation

c.286N>A

p.Ala96Thr

p.A96T

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AA-3715-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

RBP1

SNV

Missense_Mutation

c.161N>A

p.Ala54Asp

p.A54D

protein_coding

deleterious_low_confidence(0.01)

benign(0.037)

TCGA-WS-AB45-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

RBP1

SNV

Missense_Mutation

c.286G>A

p.Ala96Thr

p.A96T

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A5-A7WJ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RBP1

SNV

Missense_Mutation

novel

c.151C>T

p.Pro51Ser

p.P51S

protein_coding

tolerated_low_confidence(0.51)

benign(0.006)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RBP1

SNV

Missense_Mutation

novel

c.231G>T

p.Glu77Asp

p.E77D

protein_coding

tolerated(0.44)

benign(0)

TCGA-AP-A1E0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

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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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