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: RGL2

Gene summary for RGL2

Gene summary.

Gene information	Species	Human
	Gene symbol	RGL2
	Gene ID	5863
	Gene name	ral guanine nucleotide dissociation stimulator like 2
	Gene Alias	HKE1.5
	Cytomap	6p21.32
	Gene Type	protein-coding
	GO ID	GO:0006915
	UniProtAcc	O15211

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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
5863	RGL2	LZE4T	Human	Esophagus	ESCC	6.93e-12	6.56e-02	0.0811
5863	RGL2	LZE7T	Human	Esophagus	ESCC	5.67e-04	-9.79e-03	0.0667
5863	RGL2	LZE8T	Human	Esophagus	ESCC	6.91e-04	-4.52e-03	0.067
5863	RGL2	LZE20T	Human	Esophagus	ESCC	5.19e-08	5.59e-02	0.0662
5863	RGL2	LZE22T	Human	Esophagus	ESCC	2.23e-08	2.36e-01	0.068
5863	RGL2	LZE24T	Human	Esophagus	ESCC	5.90e-16	3.24e-01	0.0596
5863	RGL2	P1T-E	Human	Esophagus	ESCC	1.08e-06	3.80e-01	0.0875
5863	RGL2	P2T-E	Human	Esophagus	ESCC	1.46e-24	4.57e-01	0.1177
5863	RGL2	P4T-E	Human	Esophagus	ESCC	3.16e-18	2.60e-01	0.1323
5863	RGL2	P5T-E	Human	Esophagus	ESCC	2.12e-02	-1.28e-01	0.1327
5863	RGL2	P8T-E	Human	Esophagus	ESCC	3.27e-21	4.04e-01	0.0889
5863	RGL2	P9T-E	Human	Esophagus	ESCC	2.29e-07	3.39e-03	0.1131
5863	RGL2	P10T-E	Human	Esophagus	ESCC	4.55e-10	5.12e-03	0.116
5863	RGL2	P11T-E	Human	Esophagus	ESCC	1.05e-05	4.36e-01	0.1426
5863	RGL2	P12T-E	Human	Esophagus	ESCC	2.22e-16	2.54e-01	0.1122
5863	RGL2	P15T-E	Human	Esophagus	ESCC	1.37e-14	2.48e-01	0.1149
5863	RGL2	P16T-E	Human	Esophagus	ESCC	3.77e-24	2.99e-01	0.1153
5863	RGL2	P17T-E	Human	Esophagus	ESCC	1.77e-07	4.52e-01	0.1278
5863	RGL2	P19T-E	Human	Esophagus	ESCC	6.29e-06	5.40e-01	0.1662
5863	RGL2	P20T-E	Human	Esophagus	ESCC	4.16e-12	4.51e-02	0.1124

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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:000726510	Esophagus	ESCC	Ras protein signal transduction	201/8552	337/18723	1.44e-07	2.30e-06	201
GO:00465789	Esophagus	ESCC	regulation of Ras protein signal transduction	106/8552	189/18723	2.49e-03	1.08e-02	106
GO:005105610	Esophagus	ESCC	regulation of small GTPase mediated signal transduction	157/8552	302/18723	1.55e-02	4.98e-02	157
GO:000726511	Liver	Cirrhotic	Ras protein signal transduction	119/4634	337/18723	8.16e-06	1.22e-04	119
GO:000726521	Liver	HCC	Ras protein signal transduction	187/7958	337/18723	8.89e-07	1.35e-05	187
GO:004657811	Liver	HCC	regulation of Ras protein signal transduction	100/7958	189/18723	2.42e-03	1.18e-02	100
GO:00072659	Oral cavity	OSCC	Ras protein signal transduction	185/7305	337/18723	1.95e-09	4.60e-08	185
GO:00465788	Oral cavity	OSCC	regulation of Ras protein signal transduction	90/7305	189/18723	9.58e-03	3.40e-02	90
GO:000726515	Oral cavity	LP	Ras protein signal transduction	109/4623	337/18723	8.44e-04	7.36e-03	109
GO:00072658	Prostate	BPH	Ras protein signal transduction	101/3107	337/18723	5.64e-10	2.79e-08	101
GO:00510568	Prostate	BPH	regulation of small GTPase mediated signal transduction	78/3107	302/18723	2.69e-05	3.16e-04	78
GO:00465787	Prostate	BPH	regulation of Ras protein signal transduction	53/3107	189/18723	5.08e-05	5.24e-04	53
GO:00140652	Prostate	BPH	phosphatidylinositol 3-kinase signaling	35/3107	144/18723	1.10e-02	4.53e-02	35
GO:000726514	Prostate	Tumor	Ras protein signal transduction	101/3246	337/18723	6.29e-09	2.44e-07	101
GO:005105613	Prostate	Tumor	regulation of small GTPase mediated signal transduction	80/3246	302/18723	3.96e-05	4.57e-04	80
GO:004657814	Prostate	Tumor	regulation of Ras protein signal transduction	53/3246	189/18723	1.63e-04	1.46e-03	53
GO:00140651	Prostate	Tumor	phosphatidylinositol 3-kinase signaling	37/3246	144/18723	7.29e-03	3.25e-02	37
GO:000726523	Skin	cSCC	Ras protein signal transduction	132/4864	337/18723	6.17e-08	1.57e-06	132
GO:000726519	Thyroid	PTC	Ras protein signal transduction	162/5968	337/18723	3.16e-10	1.02e-08	162
GO:005105617	Thyroid	PTC	regulation of small GTPase mediated signal transduction	132/5968	302/18723	9.26e-06	1.04e-04	132

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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

RGL2

SNV

Missense_Mutation

c.616G>A

p.Asp206Asn

p.D206N

O15211

protein_coding

tolerated(0.42)

benign(0.086)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

RGL2

SNV

Missense_Mutation

c.2017C>G

p.Gln673Glu

p.Q673E

O15211

protein_coding

deleterious(0.01)

possibly_damaging(0.891)

TCGA-BH-A0BM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

RGL2

SNV

Missense_Mutation

novel

c.970N>T

p.Arg324Cys

p.R324C

O15211

protein_coding

deleterious(0)

benign(0.003)

TCGA-OL-A66N-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

RGL2

insertion

Frame_Shift_Ins

novel

c.2161_2162insGTGTTCCAGATGGTCAAATTTG

p.Met721SerfsTer43

p.M721Sfs*43

O15211

protein_coding

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

RGL2

insertion

Nonsense_Mutation

novel

c.1646_1647insAAAAGTACTAATAGAGATGCCAGGGCTGTTGGCAA

p.Cys549Ter

p.C549*

O15211

protein_coding

TCGA-BH-A0B1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin

RGL2

SNV

Missense_Mutation

c.1099N>T

p.Arg367Trp

p.R367W

O15211

protein_coding

deleterious(0)

probably_damaging(0.938)

TCGA-C5-A7UE-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

RGL2

SNV

Missense_Mutation

rs367652018

c.263C>G

p.Ser88Cys

p.S88C

O15211

protein_coding

tolerated(0.13)

benign(0.001)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

RGL2

SNV

Missense_Mutation

c.136G>C

p.Glu46Gln

p.E46Q

O15211

protein_coding

tolerated_low_confidence(0.19)

benign(0.087)

TCGA-EK-A2RN-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

RGL2

SNV

Missense_Mutation

c.962N>A

p.Arg321Gln

p.R321Q

O15211

protein_coding

deleterious_low_confidence(0.01)

benign(0.223)

TCGA-LP-A4AW-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

RGL2

SNV

Missense_Mutation

c.1783N>G

p.Pro595Ala

p.P595A

O15211

protein_coding

tolerated(0.46)

benign(0)

TCGA-LP-A5U2-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

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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