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: GPS2

Gene summary for GPS2

Gene summary.

Gene information	Species	Human
	Gene symbol	GPS2
	Gene ID	2874
	Gene name	G protein pathway suppressor 2
	Gene Alias	AMF-1
	Cytomap	17p13.1
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	Q13227

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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
2874	GPS2	LZE2T	Human	Esophagus	ESCC	5.44e-10	7.33e-01	0.082
2874	GPS2	LZE3D	Human	Esophagus	HGIN	8.88e-07	6.74e-01	0.0668
2874	GPS2	LZE4T	Human	Esophagus	ESCC	6.89e-31	7.05e-01	0.0811
2874	GPS2	LZE5T	Human	Esophagus	ESCC	8.47e-11	4.86e-01	0.0514
2874	GPS2	LZE7T	Human	Esophagus	ESCC	7.39e-21	6.82e-01	0.0667
2874	GPS2	LZE8T	Human	Esophagus	ESCC	1.17e-14	3.72e-01	0.067
2874	GPS2	LZE20T	Human	Esophagus	ESCC	4.10e-17	4.14e-01	0.0662
2874	GPS2	LZE21D1	Human	Esophagus	HGIN	7.28e-11	5.94e-01	0.0632
2874	GPS2	LZE22D1	Human	Esophagus	HGIN	6.24e-14	5.73e-01	0.0595
2874	GPS2	LZE22T	Human	Esophagus	ESCC	1.54e-17	7.33e-01	0.068
2874	GPS2	LZE24D1	Human	Esophagus	HGIN	3.66e-03	9.22e-01	0.054
2874	GPS2	LZE24T	Human	Esophagus	ESCC	5.67e-63	1.31e+00	0.0596
2874	GPS2	LZE22D3	Human	Esophagus	HGIN	1.73e-02	4.36e-01	0.0653
2874	GPS2	LZE21T	Human	Esophagus	ESCC	2.27e-11	7.55e-01	0.0655
2874	GPS2	LZE6T	Human	Esophagus	ESCC	1.60e-16	6.46e-01	0.0845
2874	GPS2	P1T-E	Human	Esophagus	ESCC	1.05e-17	5.81e-01	0.0875
2874	GPS2	P2T-E	Human	Esophagus	ESCC	3.28e-14	2.65e-01	0.1177
2874	GPS2	P4T-E	Human	Esophagus	ESCC	1.81e-30	5.50e-01	0.1323
2874	GPS2	P5T-E	Human	Esophagus	ESCC	9.20e-06	1.52e-01	0.1327
2874	GPS2	P8T-E	Human	Esophagus	ESCC	9.67e-18	3.67e-01	0.0889

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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
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:00323762	Oral cavity	NEOLP	positive regulation of cholesterol transport	11/2005	38/18723	1.60e-03	1.12e-02	11
GO:005072712	Oral cavity	NEOLP	regulation of inflammatory response	60/2005	386/18723	1.99e-03	1.33e-02	60
GO:00022242	Oral cavity	NEOLP	toll-like receptor signaling pathway	24/2005	121/18723	2.08e-03	1.38e-02	24
GO:009878013	Oral cavity	NEOLP	response to mitochondrial depolarisation	7/2005	19/18723	2.51e-03	1.59e-02	7
GO:000725422	Oral cavity	NEOLP	JNK cascade	30/2005	167/18723	3.16e-03	1.91e-02	30
GO:003210212	Oral cavity	NEOLP	negative regulation of response to external stimulus	63/2005	420/18723	3.67e-03	2.14e-02	63
GO:1902915	Oral cavity	NEOLP	negative regulation of protein polyubiquitination	5/2005	11/18723	3.72e-03	2.15e-02	5
GO:00108752	Oral cavity	NEOLP	positive regulation of cholesterol efflux	8/2005	26/18723	4.54e-03	2.54e-02	8
GO:004632921	Oral cavity	NEOLP	negative regulation of JNK cascade	10/2005	38/18723	5.51e-03	2.93e-02	10
GO:19029141	Oral cavity	NEOLP	regulation of protein polyubiquitination	8/2005	27/18723	5.85e-03	3.05e-02	8
GO:003287332	Oral cavity	NEOLP	negative regulation of stress-activated MAPK cascade	12/2005	51/18723	6.57e-03	3.36e-02	12
GO:007030332	Oral cavity	NEOLP	negative regulation of stress-activated protein kinase signaling cascade	12/2005	51/18723	6.57e-03	3.36e-02	12
GO:006220721	Oral cavity	NEOLP	regulation of pattern recognition receptor signaling pathway	20/2005	105/18723	7.48e-03	3.74e-02	20
GO:0030183	Oral cavity	NEOLP	B cell differentiation	25/2005	141/18723	7.85e-03	3.90e-02	25
GO:1900044	Oral cavity	NEOLP	regulation of protein K63-linked ubiquitination	5/2005	13/18723	8.62e-03	4.15e-02	5
GO:000225313	Oral cavity	NEOLP	activation of immune response	55/2005	375/18723	9.87e-03	4.62e-02	55
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:000726514	Prostate	Tumor	Ras protein signal transduction	101/3246	337/18723	6.29e-09	2.44e-07	101

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0516639	Esophagus	HGIN	Human T-cell leukemia virus 1 infection	51/1383	222/8465	5.84e-03	4.05e-02	3.22e-02	51
hsa05166114	Esophagus	HGIN	Human T-cell leukemia virus 1 infection	51/1383	222/8465	5.84e-03	4.05e-02	3.22e-02	51
hsa05166211	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
hsa05166310	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
hsa0516622	Liver	HCC	Human T-cell leukemia virus 1 infection	139/4020	222/8465	3.17e-06	2.79e-05	1.55e-05	139
hsa0516632	Liver	HCC	Human T-cell leukemia virus 1 infection	139/4020	222/8465	3.17e-06	2.79e-05	1.55e-05	139
hsa0516630	Oral cavity	OSCC	Human T-cell leukemia virus 1 infection	150/3704	222/8465	3.68e-13	7.26e-12	3.70e-12	150
hsa05166113	Oral cavity	OSCC	Human T-cell leukemia virus 1 infection	150/3704	222/8465	3.68e-13	7.26e-12	3.70e-12	150
hsa0516662	Oral cavity	NEOLP	Human T-cell leukemia virus 1 infection	50/1112	222/8465	6.91e-05	5.23e-04	3.29e-04	50
hsa0516672	Oral cavity	NEOLP	Human T-cell leukemia virus 1 infection	50/1112	222/8465	6.91e-05	5.23e-04	3.29e-04	50

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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

GPS2

SNV

Missense_Mutation

novel

c.632N>C

p.Arg211Thr

p.R211T

Q13227

protein_coding

deleterious(0)

benign(0.001)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

GPS2

insertion

Frame_Shift_Ins

novel

c.161_162insA

p.Glu55GlyfsTer42

p.E55Gfs*42

Q13227

protein_coding

TCGA-A2-A04V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

GPS2

insertion

Nonsense_Mutation

novel

c.181_182insAAT

p.Met60_Ser61insTer

p.M60_S61ins*

Q13227

protein_coding

TCGA-A2-A0EO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

GPS2

deletion

Frame_Shift_Del

c.310delG

p.Glu104AsnfsTer5

p.E104Nfs*5

Q13227

protein_coding

TCGA-A2-A0SY-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

arimidex

GPS2

deletion

Frame_Shift_Del

novel

c.517_536delNNNNNNNNNNNNNNNNNNNN

p.Gly173IlefsTer26

p.G173Ifs*26

Q13227

protein_coding

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

GPS2

deletion

Frame_Shift_Del

c.141_148delACAGGAGA

p.Gln48LysfsTer46

p.Q48Kfs*46

Q13227

protein_coding

TCGA-AR-A24O-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

GPS2

deletion

Frame_Shift_Del

novel

c.469delN

p.Gln157LysfsTer188

p.Q157Kfs*188

Q13227

protein_coding

TCGA-E2-A15I-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

GPS2

deletion

Frame_Shift_Del

c.281delT

p.Leu94TyrfsTer15

p.L94Yfs*15

Q13227

protein_coding

TCGA-EW-A1PG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

docetaxel

GPS2

SNV

Missense_Mutation

novel

c.709C>G

p.Gln237Glu

p.Q237E

Q13227

protein_coding

tolerated_low_confidence(0.26)

benign(0.015)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

GPS2

SNV

Missense_Mutation

rs780901898

c.902N>T

p.Ser301Leu

p.S301L

Q13227

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.776)

TCGA-MY-A5BE-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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