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	GSM4909281	Human	Breast	IDC	7.51e-07	3.37e-01	0.21
5935	RBM3	GSM4909282	Human	Breast	IDC	2.11e-04	-2.58e-01	-0.0288
5935	RBM3	GSM4909285	Human	Breast	IDC	1.93e-08	-3.44e-01	0.21
5935	RBM3	GSM4909286	Human	Breast	IDC	2.45e-05	-1.02e-01	0.1081
5935	RBM3	GSM4909294	Human	Breast	IDC	3.57e-03	-1.24e-01	0.2022
5935	RBM3	GSM4909295	Human	Breast	IDC	4.02e-02	2.81e-01	0.0898
5935	RBM3	GSM4909296	Human	Breast	IDC	4.07e-15	-4.49e-01	0.1524
5935	RBM3	GSM4909297	Human	Breast	IDC	6.89e-15	-1.64e-01	0.1517
5935	RBM3	GSM4909298	Human	Breast	IDC	2.49e-16	4.79e-01	0.1551
5935	RBM3	GSM4909305	Human	Breast	IDC	4.64e-42	7.17e-01	0.0436
5935	RBM3	GSM4909306	Human	Breast	IDC	1.22e-40	6.48e-01	0.1564
5935	RBM3	GSM4909307	Human	Breast	IDC	4.24e-08	3.45e-01	0.1569
5935	RBM3	GSM4909308	Human	Breast	IDC	5.47e-15	4.02e-01	0.158
5935	RBM3	GSM4909309	Human	Breast	IDC	8.09e-05	-4.11e-01	0.0483
5935	RBM3	GSM4909311	Human	Breast	IDC	3.00e-39	-3.98e-01	0.1534
5935	RBM3	GSM4909312	Human	Breast	IDC	1.33e-13	1.05e-01	0.1552
5935	RBM3	GSM4909315	Human	Breast	IDC	1.25e-12	3.88e-01	0.21
5935	RBM3	GSM4909316	Human	Breast	IDC	1.53e-04	1.47e-01	0.21
5935	RBM3	GSM4909317	Human	Breast	IDC	6.92e-04	2.29e-01	0.1355
5935	RBM3	GSM4909318	Human	Breast	IDC	1.65e-02	2.22e-01	0.2031

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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:003425014	Breast	IDC	positive regulation of cellular amide metabolic process	35/1434	162/18723	1.63e-08	1.16e-06	35
GO:004802414	Breast	IDC	regulation of mRNA splicing, via spliceosome	23/1434	101/18723	1.74e-06	7.28e-05	23
GO:005068413	Breast	IDC	regulation of mRNA processing	24/1434	137/18723	1.09e-04	2.04e-03	24
GO:190331113	Breast	IDC	regulation of mRNA metabolic process	40/1434	288/18723	1.79e-04	3.01e-03	40
GO:003312014	Breast	IDC	positive regulation of RNA splicing	10/1434	37/18723	3.45e-04	5.07e-03	10
GO:004802613	Breast	IDC	positive regulation of mRNA splicing, via spliceosome	6/1434	22/18723	5.12e-03	3.82e-02	6
GO:000838024	Breast	DCIS	RNA splicing	73/1390	434/18723	3.05e-11	5.08e-09	73
GO:004348424	Breast	DCIS	regulation of RNA splicing	36/1390	148/18723	1.40e-10	1.69e-08	36
GO:000037524	Breast	DCIS	RNA splicing, via transesterification reactions	58/1390	324/18723	2.89e-10	3.34e-08	58
GO:000037724	Breast	DCIS	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	57/1390	320/18723	5.01e-10	5.35e-08	57
GO:000039824	Breast	DCIS	mRNA splicing, via spliceosome	57/1390	320/18723	5.01e-10	5.35e-08	57
GO:000641724	Breast	DCIS	regulation of translation	72/1390	468/18723	2.46e-09	2.17e-07	72
GO:004572724	Breast	DCIS	positive regulation of translation	32/1390	136/18723	3.56e-09	3.10e-07	32
GO:003425023	Breast	DCIS	positive regulation of cellular amide metabolic process	34/1390	162/18723	2.60e-08	1.73e-06	34
GO:004802424	Breast	DCIS	regulation of mRNA splicing, via spliceosome	23/1390	101/18723	1.02e-06	4.04e-05	23
GO:005068423	Breast	DCIS	regulation of mRNA processing	24/1390	137/18723	6.71e-05	1.33e-03	24
GO:190331123	Breast	DCIS	regulation of mRNA metabolic process	40/1390	288/18723	9.26e-05	1.71e-03	40
GO:003312023	Breast	DCIS	positive regulation of RNA splicing	10/1390	37/18723	2.68e-04	4.06e-03	10
GO:004802623	Breast	DCIS	positive regulation of mRNA splicing, via spliceosome	6/1390	22/18723	4.39e-03	3.41e-02	6
GO:004348410	Cervix	CC	regulation of RNA splicing	42/2311	148/18723	1.25e-07	6.24e-06	42

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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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