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: RBPMS

Gene summary for RBPMS

Gene summary.

Gene information	Species	Human
	Gene symbol	RBPMS
	Gene ID	11030
	Gene name	RNA binding protein, mRNA processing factor
	Gene Alias	HERMES
	Cytomap	8p12
	Gene Type	protein-coding
	GO ID	GO:0001932
	UniProtAcc	Q93062

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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
11030	RBPMS	CCI_3	Human	Cervix	CC	3.92e-02	6.07e-01	0.516
11030	RBPMS	H2	Human	Cervix	HSIL_HPV	1.01e-04	3.05e-01	0.0632
11030	RBPMS	HTA11_78_2000001011	Human	Colorectum	AD	1.55e-08	5.84e-01	-0.1088
11030	RBPMS	HTA11_1391_2000001011	Human	Colorectum	AD	8.66e-12	5.29e-01	-0.059
11030	RBPMS	HTA11_6818_2000001021	Human	Colorectum	AD	1.98e-17	7.06e-01	0.0588
11030	RBPMS	HTA11_99999970781_79442	Human	Colorectum	MSS	1.89e-06	2.49e-01	0.294
11030	RBPMS	HTA11_99999965062_69753	Human	Colorectum	MSI-H	3.03e-04	9.58e-01	0.3487
11030	RBPMS	HTA11_99999971662_82457	Human	Colorectum	MSS	8.41e-09	3.69e-01	0.3859
11030	RBPMS	HTA11_99999973899_84307	Human	Colorectum	MSS	1.75e-07	6.02e-01	0.2585
11030	RBPMS	HTA11_99999974143_84620	Human	Colorectum	MSS	1.43e-24	6.61e-01	0.3005
11030	RBPMS	A002-C-203	Human	Colorectum	FAP	5.69e-07	5.00e-01	0.2786
11030	RBPMS	A001-C-104	Human	Colorectum	FAP	5.50e-06	3.66e-01	0.0184
11030	RBPMS	F072B	Human	Colorectum	FAP	8.78e-12	5.86e-01	0.257
11030	RBPMS	CRC-1-8810	Human	Colorectum	CRC	9.93e-07	4.06e-01	0.6257
11030	RBPMS	CRC-3-11773	Human	Colorectum	CRC	1.61e-10	5.78e-01	0.2564
11030	RBPMS	AEH-subject1	Human	Endometrium	AEH	2.23e-32	7.26e-01	-0.3059
11030	RBPMS	AEH-subject2	Human	Endometrium	AEH	1.02e-12	3.90e-01	-0.2525
11030	RBPMS	AEH-subject3	Human	Endometrium	AEH	4.16e-13	3.68e-01	-0.2576
11030	RBPMS	AEH-subject4	Human	Endometrium	AEH	4.04e-25	6.60e-01	-0.2657
11030	RBPMS	AEH-subject5	Human	Endometrium	AEH	1.41e-07	3.41e-01	-0.2953

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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
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:000697910	Cervix	CC	response to oxidative stress	102/2311	446/18723	2.99e-10	4.36e-08	102
GO:00071786	Cervix	CC	transmembrane receptor protein serine/threonine kinase signaling pathway	67/2311	355/18723	2.39e-04	2.67e-03	67
GO:000697915	Cervix	HSIL_HPV	response to oxidative stress	48/737	446/18723	2.76e-10	7.02e-08	48
GO:000717813	Cervix	HSIL_HPV	transmembrane receptor protein serine/threonine kinase signaling pathway	26/737	355/18723	1.86e-03	1.97e-02	26
GO:0006979	Colorectum	AD	response to oxidative stress	145/3918	446/18723	5.16e-09	3.23e-07	145
GO:0007178	Colorectum	AD	transmembrane receptor protein serine/threonine kinase signaling pathway	99/3918	355/18723	9.92e-04	9.28e-03	99
GO:0060390	Colorectum	AD	regulation of SMAD protein signal transduction	14/3918	31/18723	2.10e-03	1.67e-02	14
GO:0060395	Colorectum	AD	SMAD protein signal transduction	28/3918	82/18723	3.73e-03	2.63e-02	28
GO:00069792	Colorectum	MSS	response to oxidative stress	128/3467	446/18723	7.65e-08	3.81e-06	128
GO:00603901	Colorectum	MSS	regulation of SMAD protein signal transduction	14/3467	31/18723	5.98e-04	6.60e-03	14
GO:00071781	Colorectum	MSS	transmembrane receptor protein serine/threonine kinase signaling pathway	86/3467	355/18723	4.04e-03	2.95e-02	86
GO:00069793	Colorectum	MSI-H	response to oxidative stress	68/1319	446/18723	1.17e-09	1.59e-07	68
GO:00069794	Colorectum	FAP	response to oxidative stress	102/2622	446/18723	2.29e-07	1.33e-05	102
GO:00071782	Colorectum	FAP	transmembrane receptor protein serine/threonine kinase signaling pathway	81/2622	355/18723	4.28e-06	1.46e-04	81
GO:00603951	Colorectum	FAP	SMAD protein signal transduction	24/2622	82/18723	2.55e-04	3.51e-03	24
GO:00603902	Colorectum	FAP	regulation of SMAD protein signal transduction	12/2622	31/18723	5.86e-04	6.51e-03	12
GO:0060389	Colorectum	FAP	pathway-restricted SMAD protein phosphorylation	18/2622	65/18723	2.85e-03	2.19e-02	18
GO:0090092	Colorectum	FAP	regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	52/2622	256/18723	3.33e-03	2.44e-02	52
GO:0060391	Colorectum	FAP	positive regulation of SMAD protein signal transduction	7/2622	18/18723	8.10e-03	4.77e-02	7
GO:00071783	Colorectum	CRC	transmembrane receptor protein serine/threonine kinase signaling pathway	66/2078	355/18723	1.74e-05	5.28e-04	66

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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

RBPMS

SNV

Missense_Mutation

novel

c.57N>T

p.Gln19His

p.Q19H

Q93062

protein_coding

tolerated(0.19)

benign(0)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RBPMS

SNV

Missense_Mutation

novel

c.43N>A

p.Glu15Lys

p.E15K

Q93062

protein_coding

tolerated(0.51)

benign(0.037)

TCGA-MA-AA41-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

RBPMS

SNV

Missense_Mutation

novel

c.50A>C

p.Asn17Thr

p.N17T

Q93062

protein_coding

tolerated(0.32)

benign(0.005)

TCGA-MU-A8JM-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

RBPMS

SNV

Missense_Mutation

novel

c.110N>A

p.Pro37His

p.P37H

Q93062

protein_coding

deleterious(0)

possibly_damaging(0.544)

TCGA-VS-A8EL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RBPMS

SNV

Missense_Mutation

c.381N>A

p.Phe127Leu

p.F127L

Q93062

protein_coding

tolerated(0.36)

benign(0.042)

TCGA-AA-3510-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

RBPMS

SNV

Missense_Mutation

c.532C>T

p.Arg178Cys

p.R178C

Q93062

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.973)

TCGA-D5-6930-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

RBPMS

SNV

Missense_Mutation

novel

c.511G>A

p.Ala171Thr

p.A171T

Q93062

protein_coding

deleterious(0.02)

benign(0.196)

TCGA-AG-A00Y-01

Colorectum

rectum adenocarcinoma

Male

>=65

I/II

Unknown

RBPMS

SNV

Missense_Mutation

c.432N>A

p.Ser144Arg

p.S144R

Q93062

protein_coding

tolerated(0.05)

possibly_damaging(0.881)

TCGA-A5-A0G9-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

RBPMS

SNV

Missense_Mutation

c.532N>T

p.Arg178Cys

p.R178C

Q93062

protein_coding

deleterious_low_confidence(0.01)

probably_damaging(0.973)

TCGA-AJ-A3NE-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RBPMS

SNV

Missense_Mutation

c.71G>A

p.Arg24Gln

p.R24Q

Q93062

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AJ-A8CW-01

Endometrium

uterine corpus endometrioid carcinoma

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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