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: RBM3

Gene summary for RBM3

Gene summary.

Gene information	Species	Human
	Gene symbol	RBM3
	Gene ID	5935
	Gene name	RNA binding motif protein 3
	Gene Alias	IS1-RNPL
	Cytomap	Xp11.23
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	A0A024QYX3

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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
5935	RBM3	GSM5252133_BPH389PrSF	Human	Prostate	BPH	9.94e-04	7.12e-01	-0.2027
5935	RBM3	047563_1562-all-cells	Human	Prostate	BPH	1.92e-27	-1.74e-01	0.0791
5935	RBM3	Dong_P1	Human	Prostate	Tumor	8.68e-21	1.19e-01	0.035
5935	RBM3	Dong_P3	Human	Prostate	Tumor	4.53e-14	1.73e-01	0.0278
5935	RBM3	Dong_P4	Human	Prostate	Tumor	2.39e-06	1.89e-01	0.0292
5935	RBM3	Dong_P5	Human	Prostate	Tumor	6.60e-24	1.98e-01	0.053
5935	RBM3	Dong_P6	Human	Prostate	Tumor	1.50e-04	1.32e-01	0.0371
5935	RBM3	GSM5353216_PA_PB1A_Pool_1_3_S50_L002	Human	Prostate	Tumor	7.05e-05	2.96e-01	0.159
5935	RBM3	GSM5353228_PA_PR5199-640K_Pool_1_3_S108_L004	Human	Prostate	Tumor	4.34e-03	3.50e-01	0.1537
5935	RBM3	GSM5353240_PA_PR5254_T1_S15_L001	Human	Prostate	Tumor	2.31e-04	8.51e-02	0.1575
5935	RBM3	GSM5353243_PA_PR5261_T1_S23_L002	Human	Prostate	Tumor	1.08e-09	-1.81e-01	0.1545
5935	RBM3	GSM5353244_PA_PR5261_T2_S24_L002	Human	Prostate	Tumor	5.23e-09	1.93e-02	0.1569
5935	RBM3	GSM5353248_PA_PR5269_4_S28_L002	Human	Prostate	Tumor	2.06e-02	-2.47e-01	0.1541
5935	RBM3	P1_S1_AK	Human	Skin	AK	3.89e-10	-2.11e-01	-0.3399
5935	RBM3	P2_S3_AK	Human	Skin	AK	4.86e-16	-3.64e-01	-0.3287
5935	RBM3	P2_S4_SCCIS	Human	Skin	SCCIS	5.48e-15	-4.28e-01	-0.3043
5935	RBM3	P3_S6_AK	Human	Skin	AK	5.15e-03	-3.13e-01	-0.3256
5935	RBM3	P4_S8_cSCC	Human	Skin	cSCC	4.97e-13	-2.06e-01	-0.3095
5935	RBM3	P5_S10_cSCC	Human	Skin	cSCC	1.88e-45	-6.11e-01	-0.299
5935	RBM3	P1_cSCC	Human	Skin	cSCC	1.82e-59	2.87e+00	0.0292

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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
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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:00083809	Breast	Precancer	RNA splicing	65/1080	434/18723	1.27e-12	2.53e-10	65
GO:00434849	Breast	Precancer	regulation of RNA splicing	34/1080	148/18723	2.66e-12	4.75e-10	34
GO:00064179	Breast	Precancer	regulation of translation	67/1080	468/18723	4.71e-12	7.64e-10	67
GO:00457279	Breast	Precancer	positive regulation of translation	32/1080	136/18723	5.89e-12	9.27e-10	32
GO:00003759	Breast	Precancer	RNA splicing, via transesterification reactions	52/1080	324/18723	1.74e-11	2.22e-09	52
GO:00003779	Breast	Precancer	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	51/1080	320/18723	3.55e-11	4.04e-09	51
GO:00003989	Breast	Precancer	mRNA splicing, via spliceosome	51/1080	320/18723	3.55e-11	4.04e-09	51
GO:00342509	Breast	Precancer	positive regulation of cellular amide metabolic process	33/1080	162/18723	1.72e-10	1.77e-08	33
GO:00480249	Breast	Precancer	regulation of mRNA splicing, via spliceosome	22/1080	101/18723	5.29e-08	3.18e-06	22
GO:19033118	Breast	Precancer	regulation of mRNA metabolic process	38/1080	288/18723	1.63e-06	5.97e-05	38
GO:00506848	Breast	Precancer	regulation of mRNA processing	23/1080	137/18723	3.49e-06	1.13e-04	23
GO:00331207	Breast	Precancer	positive regulation of RNA splicing	9/1080	37/18723	1.96e-04	3.10e-03	9
GO:00480266	Breast	Precancer	positive regulation of mRNA splicing, via spliceosome	5/1080	22/18723	7.32e-03	4.88e-02	5
GO:000838014	Breast	IDC	RNA splicing	73/1434	434/18723	1.27e-10	1.57e-08	73
GO:004348414	Breast	IDC	regulation of RNA splicing	36/1434	148/18723	3.32e-10	3.77e-08	36
GO:000037514	Breast	IDC	RNA splicing, via transesterification reactions	58/1434	324/18723	9.44e-10	9.58e-08	58
GO:000037714	Breast	IDC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	57/1434	320/18723	1.60e-09	1.49e-07	57
GO:000039814	Breast	IDC	mRNA splicing, via spliceosome	57/1434	320/18723	1.60e-09	1.49e-07	57
GO:000641714	Breast	IDC	regulation of translation	74/1434	468/18723	1.67e-09	1.53e-07	74
GO:004572714	Breast	IDC	positive regulation of translation	33/1434	136/18723	1.92e-09	1.73e-07	33

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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

RBM3

SNV

Missense_Mutation

c.185N>A

p.Val62Asp

p.V62D

P98179

protein_coding

tolerated(1)

benign(0)

TCGA-E9-A1R2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

taxotere

RBM3

SNV

Missense_Mutation

c.287N>T

p.Ala96Val

p.A96V

P98179

protein_coding

tolerated(0.08)

benign(0.003)

TCGA-EK-A2H1-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cetuximab

RBM3

SNV

Missense_Mutation

novel

c.269N>C

p.Arg90Thr

p.R90T

P98179

protein_coding

deleterious(0.01)

possibly_damaging(0.587)

TCGA-VS-A94Z-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RBM3

SNV

Missense_Mutation

rs782287047

c.295N>T

p.Arg99Cys

p.R99C

P98179

protein_coding

tolerated(0.14)

benign(0)

TCGA-D5-6927-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

RBM3

SNV

Missense_Mutation

novel

c.42N>A

p.Asn14Lys

p.N14K

P98179

protein_coding

deleterious(0.01)

possibly_damaging(0.9)

TCGA-A5-A1OG-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Chemotherapy

taxol

RBM3

SNV

Missense_Mutation

novel

c.392N>A

p.Arg131His

p.R131H

P98179

protein_coding

tolerated(0.27)

benign(0.078)

TCGA-AJ-A8CW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RBM3

SNV

Missense_Mutation

novel

c.305N>T

p.Ser102Ile

p.S102I

P98179

protein_coding

deleterious(0.02)

benign(0)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

RBM3

SNV

Missense_Mutation

c.113T>G

p.Val38Gly

p.V38G

P98179

protein_coding

deleterious(0)

probably_damaging(0.975)

TCGA-BS-A0UV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

RBM3

SNV

Missense_Mutation

c.284N>A

p.Gly95Glu

p.G95E

P98179

protein_coding

tolerated(0.28)

possibly_damaging(0.604)

TCGA-D1-A17F-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

RBM3

SNV

Missense_Mutation

novel

c.88N>A

p.Gly30Arg

p.G30R

P98179

protein_coding

tolerated(0.11)

possibly_damaging(0.729)

TCGA-EO-A22X-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unspecific

Carboplatin

Complete Response

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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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