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:00022215	Thyroid	PTC	pattern recognition receptor signaling pathway	77/5968	172/18723	2.56e-04	1.84e-03	77
GO:0071356111	Thyroid	PTC	cellular response to tumor necrosis factor	96/5968	229/18723	8.24e-04	5.10e-03	96
GO:000725419	Thyroid	PTC	JNK cascade	73/5968	167/18723	8.41e-04	5.17e-03	73
GO:0070302110	Thyroid	PTC	regulation of stress-activated protein kinase signaling cascade	83/5968	195/18723	1.04e-03	6.21e-03	83
GO:00607597	Thyroid	PTC	regulation of response to cytokine stimulus	70/5968	162/18723	1.54e-03	8.58e-03	70
GO:0032872110	Thyroid	PTC	regulation of stress-activated MAPK cascade	81/5968	192/18723	1.62e-03	8.95e-03	81
GO:0043409112	Thyroid	PTC	negative regulation of MAPK cascade	76/5968	180/18723	2.15e-03	1.14e-02	76
GO:00019596	Thyroid	PTC	regulation of cytokine-mediated signaling pathway	64/5968	150/18723	3.43e-03	1.66e-02	64
GO:004559814	Thyroid	PTC	regulation of fat cell differentiation	59/5968	139/18723	5.50e-03	2.50e-02	59
GO:003320916	Thyroid	PTC	tumor necrosis factor-mediated signaling pathway	44/5968	99/18723	5.77e-03	2.60e-02	44
GO:190332034	Thyroid	ATC	regulation of protein modification by small protein conjugation or removal	152/6293	242/18723	9.76e-21	1.71e-18	152
GO:003139634	Thyroid	ATC	regulation of protein ubiquitination	132/6293	210/18723	3.13e-18	3.98e-16	132
GO:0000209110	Thyroid	ATC	protein polyubiquitination	134/6293	236/18723	1.86e-13	9.20e-12	134
GO:003139734	Thyroid	ATC	negative regulation of protein ubiquitination	56/6293	83/18723	2.90e-10	8.20e-09	56
GO:190332135	Thyroid	ATC	negative regulation of protein modification by small protein conjugation or removal	60/6293	95/18723	3.53e-09	8.14e-08	60
GO:0030522112	Thyroid	ATC	intracellular receptor signaling pathway	134/6293	265/18723	7.58e-09	1.63e-07	134
GO:003109826	Thyroid	ATC	stress-activated protein kinase signaling cascade	120/6293	247/18723	7.06e-07	9.46e-06	120
GO:005140326	Thyroid	ATC	stress-activated MAPK cascade	115/6293	239/18723	2.17e-06	2.58e-05	115
GO:003461228	Thyroid	ATC	response to tumor necrosis factor	116/6293	253/18723	3.22e-05	2.68e-04	116
GO:004544423	Thyroid	ATC	fat cell differentiation	105/6293	229/18723	7.42e-05	5.62e-04	105

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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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