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: RBM23

Gene summary for RBM23

Gene summary.

Gene information	Species	Human
	Gene symbol	RBM23
	Gene ID	55147
	Gene name	RNA binding motif protein 23
	Gene Alias	CAPERbeta
	Cytomap	14q11.2
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	A0A0S2Z5D9

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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
55147	RBM23	HTA11_3410_2000001011	Human	Colorectum	AD	2.70e-02	1.26e-01	0.0155
55147	RBM23	HTA11_411_2000001011	Human	Colorectum	SER	6.36e-03	6.16e-01	-0.2602
55147	RBM23	HTA11_696_2000001011	Human	Colorectum	AD	8.83e-07	3.48e-01	-0.1464
55147	RBM23	HTA11_1391_2000001011	Human	Colorectum	AD	7.60e-04	3.59e-01	-0.059
55147	RBM23	HTA11_99999965104_69814	Human	Colorectum	MSS	1.12e-09	6.10e-01	0.281
55147	RBM23	A002-C-016	Human	Colorectum	FAP	2.87e-03	-8.57e-02	0.0521
55147	RBM23	LZE4T	Human	Esophagus	ESCC	2.97e-24	6.70e-01	0.0811
55147	RBM23	LZE5T	Human	Esophagus	ESCC	5.61e-05	2.68e-01	0.0514
55147	RBM23	LZE7T	Human	Esophagus	ESCC	2.46e-03	2.73e-01	0.0667
55147	RBM23	LZE8T	Human	Esophagus	ESCC	4.76e-09	2.52e-01	0.067
55147	RBM23	LZE20T	Human	Esophagus	ESCC	4.65e-04	2.37e-01	0.0662
55147	RBM23	LZE22T	Human	Esophagus	ESCC	1.50e-05	3.96e-01	0.068
55147	RBM23	LZE24T	Human	Esophagus	ESCC	1.05e-19	5.14e-01	0.0596
55147	RBM23	LZE21T	Human	Esophagus	ESCC	4.36e-06	5.62e-01	0.0655
55147	RBM23	LZE6T	Human	Esophagus	ESCC	6.70e-04	2.45e-01	0.0845
55147	RBM23	P1T-E	Human	Esophagus	ESCC	2.95e-08	5.89e-01	0.0875
55147	RBM23	P2T-E	Human	Esophagus	ESCC	5.55e-56	9.90e-01	0.1177
55147	RBM23	P4T-E	Human	Esophagus	ESCC	2.89e-32	5.10e-01	0.1323
55147	RBM23	P5T-E	Human	Esophagus	ESCC	6.22e-10	2.05e-01	0.1327
55147	RBM23	P8T-E	Human	Esophagus	ESCC	3.01e-49	8.47e-01	0.0889

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:0008380	Colorectum	AD	RNA splicing	169/3918	434/18723	3.59e-18	2.04e-15	169
GO:0000377	Colorectum	AD	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	130/3918	320/18723	5.88e-16	2.16e-13	130
GO:0000398	Colorectum	AD	mRNA splicing, via spliceosome	130/3918	320/18723	5.88e-16	2.16e-13	130
GO:0000375	Colorectum	AD	RNA splicing, via transesterification reactions	131/3918	324/18723	7.11e-16	2.22e-13	131
GO:1903311	Colorectum	AD	regulation of mRNA metabolic process	117/3918	288/18723	1.69e-14	4.23e-12	117
GO:0043484	Colorectum	AD	regulation of RNA splicing	70/3918	148/18723	6.47e-13	1.16e-10	70
GO:0048024	Colorectum	AD	regulation of mRNA splicing, via spliceosome	50/3918	101/18723	1.62e-10	1.56e-08	50
GO:0050684	Colorectum	AD	regulation of mRNA processing	61/3918	137/18723	4.23e-10	3.58e-08	61
GO:00083801	Colorectum	SER	RNA splicing	123/2897	434/18723	3.84e-12	8.41e-10	123
GO:00003751	Colorectum	SER	RNA splicing, via transesterification reactions	90/2897	324/18723	8.68e-09	7.50e-07	90
GO:00003771	Colorectum	SER	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	89/2897	320/18723	9.82e-09	8.14e-07	89
GO:00003981	Colorectum	SER	mRNA splicing, via spliceosome	89/2897	320/18723	9.82e-09	8.14e-07	89
GO:00434841	Colorectum	SER	regulation of RNA splicing	49/2897	148/18723	7.02e-08	4.49e-06	49
GO:19033111	Colorectum	SER	regulation of mRNA metabolic process	78/2897	288/18723	2.61e-07	1.43e-05	78
GO:00480241	Colorectum	SER	regulation of mRNA splicing, via spliceosome	35/2897	101/18723	1.52e-06	6.85e-05	35
GO:00506841	Colorectum	SER	regulation of mRNA processing	42/2897	137/18723	5.57e-06	2.01e-04	42
GO:00083802	Colorectum	MSS	RNA splicing	159/3467	434/18723	1.75e-19	1.22e-16	159
GO:19033112	Colorectum	MSS	regulation of mRNA metabolic process	115/3467	288/18723	1.23e-17	6.41e-15	115
GO:00003772	Colorectum	MSS	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	121/3467	320/18723	2.52e-16	8.27e-14	121
GO:00003982	Colorectum	MSS	mRNA splicing, via spliceosome	121/3467	320/18723	2.52e-16	8.27e-14	121

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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

RBM23

deletion

Frame_Shift_Del

novel

c.1237delN

p.Ala413LeufsTer2

p.A413Lfs*2

Q86U06

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

RBM23

SNV

Missense_Mutation

novel

c.1249N>G

p.Leu417Val

p.L417V

Q86U06

protein_coding

tolerated(0.26)

benign(0.074)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

RBM23

SNV

Missense_Mutation

novel

c.874N>G

p.Ile292Val

p.I292V

Q86U06

protein_coding

tolerated(0.13)

benign(0.124)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

RBM23

SNV

Missense_Mutation

novel

c.425N>A

p.Ser142Asn

p.S142N

Q86U06

protein_coding

tolerated(0.06)

benign(0.444)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

RBM23

SNV

Missense_Mutation

novel

c.56N>C

p.Lys19Thr

p.K19T

Q86U06

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.702)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

RBM23

SNV

Missense_Mutation

novel

c.1232C>A

p.Pro411Gln

p.P411Q

Q86U06

protein_coding

tolerated(0.06)

benign(0.308)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

RBM23

SNV

Missense_Mutation

novel

c.407G>T

p.Arg136Met

p.R136M

Q86U06

protein_coding

deleterious(0.01)

benign(0.007)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RBM23

SNV

Missense_Mutation

rs373264361

c.269G>A

p.Arg90Gln

p.R90Q

Q86U06

protein_coding

tolerated(0.23)

benign(0)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

RBM23

SNV

Missense_Mutation

c.727N>T

p.Ala243Ser

p.A243S

Q86U06

protein_coding

tolerated(0.06)

possibly_damaging(0.673)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

RBM23

SNV

Missense_Mutation

c.101N>T

p.Tyr34Phe

p.Y34F

Q86U06

protein_coding

tolerated_low_confidence(0.11)

benign(0.011)

TCGA-AP-A059-01

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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