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:00463946	Breast	Precancer	carboxylic acid biosynthetic process	32/1080	314/18723	1.30e-03	1.38e-02	32
GO:00723304	Breast	Precancer	monocarboxylic acid biosynthetic process	24/1080	214/18723	1.41e-03	1.48e-02	24
GO:00160536	Breast	Precancer	organic acid biosynthetic process	32/1080	316/18723	1.44e-03	1.50e-02	32
GO:000164912	Breast	IDC	osteoblast differentiation	35/1434	229/18723	6.64e-05	1.35e-03	35
GO:000150311	Breast	IDC	ossification	50/1434	408/18723	6.51e-04	8.04e-03	50
GO:007233012	Breast	IDC	monocarboxylic acid biosynthetic process	29/1434	214/18723	1.91e-03	1.83e-02	29
GO:001605313	Breast	IDC	organic acid biosynthetic process	39/1434	316/18723	2.13e-03	1.99e-02	39
GO:004639413	Breast	IDC	carboxylic acid biosynthetic process	38/1434	314/18723	3.39e-03	2.83e-02	38
GO:000164921	Breast	DCIS	osteoblast differentiation	32/1390	229/18723	4.00e-04	5.48e-03	32
GO:001605322	Breast	DCIS	organic acid biosynthetic process	38/1390	316/18723	2.22e-03	2.04e-02	38
GO:007233022	Breast	DCIS	monocarboxylic acid biosynthetic process	28/1390	214/18723	2.43e-03	2.18e-02	28
GO:004639422	Breast	DCIS	carboxylic acid biosynthetic process	37/1390	314/18723	3.56e-03	2.92e-02	37
GO:000150321	Breast	DCIS	ossification	45/1390	408/18723	4.98e-03	3.72e-02	45
GO:00064029	Cervix	CC	mRNA catabolic process	56/2311	232/18723	4.81e-07	1.83e-05	56
GO:19033119	Cervix	CC	regulation of mRNA metabolic process	64/2311	288/18723	1.71e-06	5.64e-05	64
GO:00064019	Cervix	CC	RNA catabolic process	62/2311	278/18723	2.18e-06	6.56e-05	62
GO:00610139	Cervix	CC	regulation of mRNA catabolic process	38/2311	166/18723	1.07e-04	1.36e-03	38
GO:00467008	Cervix	CC	heterocycle catabolic process	80/2311	445/18723	3.23e-04	3.42e-03	80
GO:00346559	Cervix	CC	nucleobase-containing compound catabolic process	74/2311	407/18723	3.77e-04	3.88e-03	74
GO:00434889	Cervix	CC	regulation of mRNA stability	35/2311	158/18723	3.80e-04	3.89e-03	35

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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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