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: RBM5

Gene summary for RBM5

Gene summary.

Gene information	Species	Human
	Gene symbol	RBM5
	Gene ID	10181
	Gene name	RNA binding motif protein 5
	Gene Alias	G15
	Cytomap	3p21.31
	Gene Type	protein-coding
	GO ID	GO:0000245
	UniProtAcc	A0A024R2U6

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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
10181	RBM5	LZE4T	Human	Esophagus	ESCC	2.79e-25	4.32e-01	0.0811
10181	RBM5	LZE5T	Human	Esophagus	ESCC	4.30e-10	3.52e-01	0.0514
10181	RBM5	LZE7T	Human	Esophagus	ESCC	1.19e-09	2.77e-01	0.0667
10181	RBM5	LZE8T	Human	Esophagus	ESCC	1.48e-07	7.36e-02	0.067
10181	RBM5	LZE20T	Human	Esophagus	ESCC	2.95e-05	1.02e-01	0.0662
10181	RBM5	LZE21D1	Human	Esophagus	HGIN	6.42e-05	5.66e-01	0.0632
10181	RBM5	LZE22T	Human	Esophagus	ESCC	6.63e-08	3.03e-01	0.068
10181	RBM5	LZE24T	Human	Esophagus	ESCC	2.17e-18	2.71e-01	0.0596
10181	RBM5	LZE21T	Human	Esophagus	ESCC	8.87e-05	9.24e-02	0.0655
10181	RBM5	P1T-E	Human	Esophagus	ESCC	1.42e-04	2.10e-01	0.0875
10181	RBM5	P2T-E	Human	Esophagus	ESCC	7.24e-28	2.26e-01	0.1177
10181	RBM5	P4T-E	Human	Esophagus	ESCC	1.37e-13	2.43e-01	0.1323
10181	RBM5	P5T-E	Human	Esophagus	ESCC	8.73e-19	1.14e-01	0.1327
10181	RBM5	P8T-E	Human	Esophagus	ESCC	1.39e-27	2.96e-01	0.0889
10181	RBM5	P9T-E	Human	Esophagus	ESCC	4.95e-20	2.75e-01	0.1131
10181	RBM5	P10T-E	Human	Esophagus	ESCC	1.25e-21	3.50e-01	0.116
10181	RBM5	P11T-E	Human	Esophagus	ESCC	4.19e-09	3.77e-01	0.1426
10181	RBM5	P12T-E	Human	Esophagus	ESCC	6.09e-22	4.72e-01	0.1122
10181	RBM5	P15T-E	Human	Esophagus	ESCC	1.59e-19	2.68e-01	0.1149
10181	RBM5	P16T-E	Human	Esophagus	ESCC	1.76e-21	2.80e-01	0.1153

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0071826111	Esophagus	ESCC	ribonucleoprotein complex subunit organization	166/8552	227/18723	2.94e-17	2.42e-15	166
GO:0043484111	Esophagus	ESCC	regulation of RNA splicing	116/8552	148/18723	3.18e-16	2.38e-14	116
GO:0050684110	Esophagus	ESCC	regulation of mRNA processing	109/8552	137/18723	3.51e-16	2.59e-14	109
GO:0022618111	Esophagus	ESCC	ribonucleoprotein complex assembly	159/8552	220/18723	8.19e-16	5.71e-14	159
GO:0048024111	Esophagus	ESCC	regulation of mRNA splicing, via spliceosome	78/8552	101/18723	8.72e-11	2.66e-09	78
GO:000038019	Esophagus	ESCC	alternative mRNA splicing, via spliceosome	55/8552	77/18723	4.07e-06	4.38e-05	55
GO:000038119	Esophagus	ESCC	regulation of alternative mRNA splicing, via spliceosome	40/8552	60/18723	8.30e-04	4.28e-03	40
GO:000024514	Esophagus	ESCC	spliceosomal complex assembly	48/8552	79/18723	4.93e-03	1.89e-02	48
GO:19033116	Liver	NAFLD	regulation of mRNA metabolic process	66/1882	288/18723	1.06e-10	2.96e-08	66
GO:00434847	Liver	NAFLD	regulation of RNA splicing	35/1882	148/18723	1.14e-06	5.55e-05	35
GO:00506846	Liver	NAFLD	regulation of mRNA processing	33/1882	137/18723	1.47e-06	6.73e-05	33
GO:00480247	Liver	NAFLD	regulation of mRNA splicing, via spliceosome	26/1882	101/18723	5.10e-06	1.89e-04	26
GO:00226137	Liver	NAFLD	ribonucleoprotein complex biogenesis	76/1882	463/18723	1.19e-05	3.67e-04	76
GO:00226187	Liver	NAFLD	ribonucleoprotein complex assembly	42/1882	220/18723	3.40e-05	8.80e-04	42
GO:00083807	Liver	NAFLD	RNA splicing	70/1882	434/18723	4.62e-05	1.10e-03	70
GO:00003806	Liver	NAFLD	alternative mRNA splicing, via spliceosome	20/1882	77/18723	5.30e-05	1.21e-03	20
GO:00003816	Liver	NAFLD	regulation of alternative mRNA splicing, via spliceosome	17/1882	60/18723	5.81e-05	1.30e-03	17
GO:00718267	Liver	NAFLD	ribonucleoprotein complex subunit organization	42/1882	227/18723	7.21e-05	1.51e-03	42
GO:00003777	Liver	NAFLD	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	51/1882	320/18723	6.21e-04	8.18e-03	51
GO:00003987	Liver	NAFLD	mRNA splicing, via spliceosome	51/1882	320/18723	6.21e-04	8.18e-03	51

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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

RBM5

SNV

Missense_Mutation

novel

c.1909N>A

p.Glu637Lys

p.E637K

P52756

protein_coding

tolerated(0.36)

benign(0.012)

TCGA-A2-A3XZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

RBM5

SNV

Missense_Mutation

novel

c.443A>G

p.Tyr148Cys

p.Y148C

P52756

protein_coding

tolerated(0.09)

probably_damaging(0.998)

TCGA-OL-A66I-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

RBM5

insertion

In_Frame_Ins

novel

c.476_477insAGTGAGAGA

p.Ala159_Asn160insValArgAsp

p.A159_N160insVRD

P52756

protein_coding

TCGA-A8-A097-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

RBM5

insertion

Frame_Shift_Ins

novel

c.477_478insAGAGACTCCCATCTTA

p.Asn160ArgfsTer22

p.N160Rfs*22

P52756

protein_coding

TCGA-A8-A097-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

RBM5

insertion

Nonsense_Mutation

novel

c.497_498insAGTGGCATTAACATTCTAATCTCCTTGAGAATGCCTTTTATAG

p.Gln167ValfsTer6

p.Q167Vfs*6

P52756

protein_coding

TCGA-BH-A0EB-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

RBM5

deletion

Frame_Shift_Del

novel

c.1046delN

p.Ser350ValfsTer52

p.S350Vfs*52

P52756

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

RBM5

SNV

Missense_Mutation

rs147593355

c.1217C>T

p.Ala406Val

p.A406V

P52756

protein_coding

tolerated(0.21)

benign(0.039)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RBM5

SNV

Missense_Mutation

rs145873632

c.2185G>A

p.Gly729Ser

p.G729S

P52756

protein_coding

tolerated(0.25)

benign(0.083)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RBM5

SNV

Missense_Mutation

novel

c.593N>C

p.Arg198Thr

p.R198T

P52756

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-C5-A1M7-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

RBM5

SNV

Missense_Mutation

novel

c.2111N>A

p.Arg704Gln

p.R704Q

P52756

protein_coding

deleterious(0)

probably_damaging(0.963)

TCGA-C5-A7UI-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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