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: GPSM2

Gene summary for GPSM2

Gene summary.

Gene information	Species	Human
	Gene symbol	GPSM2
	Gene ID	29899
	Gene name	G protein signaling modulator 2
	Gene Alias	CMCS
	Cytomap	1p13.3
	Gene Type	protein-coding
	GO ID	GO:0000132
	UniProtAcc	A0A024R0F8

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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
29899	GPSM2	CA_HPV_3	Human	Cervix	CC	1.23e-05	2.70e-01	0.0414
29899	GPSM2	CCI_1	Human	Cervix	CC	3.07e-02	4.69e-01	0.528
29899	GPSM2	CCI_2	Human	Cervix	CC	2.41e-03	6.30e-01	0.5249
29899	GPSM2	CCI_3	Human	Cervix	CC	3.70e-02	5.02e-01	0.516
29899	GPSM2	LZE22T	Human	Esophagus	ESCC	2.93e-03	3.12e-01	0.068
29899	GPSM2	P2T-E	Human	Esophagus	ESCC	7.79e-04	2.63e-01	0.1177
29899	GPSM2	P4T-E	Human	Esophagus	ESCC	1.53e-09	2.46e-01	0.1323
29899	GPSM2	P5T-E	Human	Esophagus	ESCC	1.33e-11	2.47e-01	0.1327
29899	GPSM2	P8T-E	Human	Esophagus	ESCC	1.71e-02	1.11e-02	0.0889
29899	GPSM2	P9T-E	Human	Esophagus	ESCC	1.14e-02	1.49e-01	0.1131
29899	GPSM2	P10T-E	Human	Esophagus	ESCC	3.49e-05	2.99e-01	0.116
29899	GPSM2	P11T-E	Human	Esophagus	ESCC	5.91e-09	2.34e-01	0.1426
29899	GPSM2	P12T-E	Human	Esophagus	ESCC	2.86e-03	1.88e-01	0.1122
29899	GPSM2	P15T-E	Human	Esophagus	ESCC	2.78e-02	1.50e-01	0.1149
29899	GPSM2	P17T-E	Human	Esophagus	ESCC	4.31e-03	5.52e-01	0.1278
29899	GPSM2	P19T-E	Human	Esophagus	ESCC	3.01e-04	5.69e-01	0.1662
29899	GPSM2	P20T-E	Human	Esophagus	ESCC	6.85e-22	6.69e-01	0.1124
29899	GPSM2	P21T-E	Human	Esophagus	ESCC	1.72e-11	3.01e-01	0.1617
29899	GPSM2	P23T-E	Human	Esophagus	ESCC	1.28e-10	6.15e-01	0.108
29899	GPSM2	P24T-E	Human	Esophagus	ESCC	3.54e-06	2.85e-01	0.1287

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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
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:0051651111	Esophagus	ESCC	maintenance of location in cell	126/8552	214/18723	6.57e-05	5.00e-04	126
GO:009016914	Esophagus	ESCC	regulation of spindle assembly	21/8552	25/18723	9.12e-05	6.54e-04	21
GO:190437719	Esophagus	ESCC	positive regulation of protein localization to cell periphery	47/8552	69/18723	1.37e-04	9.27e-04	47
GO:0000132	Esophagus	ESCC	establishment of mitotic spindle orientation	23/8552	30/18723	5.47e-04	3.00e-03	23
GO:00400011	Esophagus	ESCC	establishment of mitotic spindle localization	26/8552	35/18723	5.57e-04	3.04e-03	26
GO:00512941	Esophagus	ESCC	establishment of spindle orientation	27/8552	37/18723	7.00e-04	3.66e-03	27
GO:00328864	Esophagus	ESCC	regulation of microtubule-based process	134/8552	240/18723	9.44e-04	4.80e-03	134
GO:00516533	Esophagus	ESCC	spindle localization	37/8552	56/18723	1.65e-03	7.65e-03	37
GO:19021174	Esophagus	ESCC	positive regulation of organelle assembly	42/8552	67/18723	3.72e-03	1.52e-02	42
GO:0051293	Esophagus	ESCC	establishment of spindle localization	33/8552	51/18723	4.77e-03	1.85e-02	33
GO:190382922	Liver	HCC	positive regulation of cellular protein localization	199/7958	276/18723	1.15e-23	2.62e-21	199
GO:199077821	Liver	HCC	protein localization to cell periphery	200/7958	333/18723	6.07e-11	2.23e-09	200
GO:005165621	Liver	HCC	establishment of organelle localization	226/7958	390/18723	4.15e-10	1.34e-08	226
GO:005149522	Liver	HCC	positive regulation of cytoskeleton organization	138/7958	226/18723	1.26e-08	3.12e-07	138
GO:000705111	Liver	HCC	spindle organization	116/7958	184/18723	1.40e-08	3.40e-07	116
GO:000716322	Liver	HCC	establishment or maintenance of cell polarity	133/7958	218/18723	2.48e-08	5.73e-07	133
GO:190437521	Liver	HCC	regulation of protein localization to cell periphery	83/7958	125/18723	5.60e-08	1.19e-06	83
GO:000705211	Liver	HCC	mitotic spindle organization	80/7958	120/18723	7.43e-08	1.50e-06	80
GO:005123521	Liver	HCC	maintenance of location	185/7958	327/18723	1.70e-07	3.12e-06	185
GO:190285011	Liver	HCC	microtubule cytoskeleton organization involved in mitosis	93/7958	147/18723	2.91e-07	5.09e-06	93

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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

GPSM2

SNV

Missense_Mutation

c.1114C>G

p.Gln372Glu

p.Q372E

P81274

protein_coding

tolerated(0.15)

benign(0)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GPSM2

SNV

Missense_Mutation

c.1463G>C

p.Gly488Ala

p.G488A

P81274

protein_coding

tolerated(0.14)

benign(0.011)

TCGA-AO-A0J3-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyclophosphamide

GPSM2

SNV

Missense_Mutation

c.1629C>A

p.Asn543Lys

p.N543K

P81274

protein_coding

tolerated(0.49)

benign(0.015)

TCGA-AR-A0TX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GPSM2

SNV

Missense_Mutation

rs867670266

c.815N>T

p.Ala272Val

p.A272V

P81274

protein_coding

tolerated(0.06)

probably_damaging(0.948)

TCGA-B6-A0IA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

GPSM2

SNV

Missense_Mutation

c.1672N>A

p.Arg558Ser

p.R558S

P81274

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A1FC-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GPSM2

SNV

Missense_Mutation

c.1258N>A

p.Glu420Lys

p.E420K

P81274

protein_coding

tolerated(0.1)

benign(0.08)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GPSM2

SNV

Missense_Mutation

c.970N>A

p.Ala324Thr

p.A324T

P81274

protein_coding

deleterious(0.02)

benign(0.241)

TCGA-E2-A152-01

Breast

breast invasive carcinoma

Female

<65

I/II

Targeted Molecular therapy

trastuzumab

GPSM2

SNV

Missense_Mutation

c.1778C>A

p.Ala593Asp

p.A593D

P81274

protein_coding

deleterious(0.03)

benign(0.078)

TCGA-E2-A15L-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

GPSM2

SNV

Missense_Mutation

novel

c.1525T>C

p.Cys509Arg

p.C509R

P81274

protein_coding

deleterious(0)

possibly_damaging(0.677)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GPSM2

SNV

Missense_Mutation

novel

c.1673G>C

p.Arg558Pro

p.R558P

P81274

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-DS-A1OC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

gemcitabine

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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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