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: MTSS1

Gene summary for MTSS1

Gene summary.

Gene information	Species	Human
	Gene symbol	MTSS1
	Gene ID	9788
	Gene name	MTSS I-BAR domain containing 1
	Gene Alias	MIM
	Cytomap	8q24.13
	Gene Type	protein-coding
	GO ID	GO:0001655
	UniProtAcc	O43312

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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
9788	MTSS1	CA_HPV_1	Human	Cervix	CC	9.58e-07	-1.98e-01	0.0264
9788	MTSS1	CCI_1	Human	Cervix	CC	6.66e-11	1.37e+00	0.528
9788	MTSS1	CCI_2	Human	Cervix	CC	6.06e-07	1.11e+00	0.5249
9788	MTSS1	CCI_3	Human	Cervix	CC	6.23e-11	1.32e+00	0.516
9788	MTSS1	Tumor	Human	Cervix	CC	1.83e-04	3.15e-01	0.1241
9788	MTSS1	sample3	Human	Cervix	CC	4.56e-12	4.30e-01	0.1387
9788	MTSS1	H2	Human	Cervix	HSIL_HPV	6.48e-04	-1.83e-01	0.0632
9788	MTSS1	T3	Human	Cervix	CC	1.06e-08	4.04e-01	0.1389
9788	MTSS1	HTA11_3410_2000001011	Human	Colorectum	AD	1.48e-06	-4.10e-01	0.0155
9788	MTSS1	HTA11_866_3004761011	Human	Colorectum	AD	3.18e-05	-4.38e-01	0.096
9788	MTSS1	HTA11_99999970781_79442	Human	Colorectum	MSS	6.66e-12	-5.54e-01	0.294
9788	MTSS1	HTA11_99999965104_69814	Human	Colorectum	MSS	3.22e-06	-5.88e-01	0.281
9788	MTSS1	HTA11_99999971662_82457	Human	Colorectum	MSS	1.45e-03	-4.32e-01	0.3859
9788	MTSS1	HTA11_99999973899_84307	Human	Colorectum	MSS	3.90e-12	-8.22e-01	0.2585
9788	MTSS1	HTA11_99999974143_84620	Human	Colorectum	MSS	8.41e-15	-6.20e-01	0.3005
9788	MTSS1	F007	Human	Colorectum	FAP	3.79e-02	-2.37e-01	0.1176
9788	MTSS1	A002-C-010	Human	Colorectum	FAP	1.82e-02	-2.03e-01	0.242
9788	MTSS1	A001-C-207	Human	Colorectum	FAP	2.05e-04	-2.78e-01	0.1278
9788	MTSS1	A015-C-203	Human	Colorectum	FAP	6.60e-27	-4.79e-01	-0.1294
9788	MTSS1	A015-C-204	Human	Colorectum	FAP	3.36e-08	-3.59e-01	-0.0228

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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
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:003433211	Liver	HCC	adherens junction organization	30/7958	49/18723	6.31e-03	2.57e-02	30
GO:003223122	Liver	HCC	regulation of actin filament bundle assembly	57/7958	105/18723	9.73e-03	3.66e-02	57
GO:00070158	Lung	IAC	actin filament organization	92/2061	442/18723	1.01e-09	1.93e-07	92
GO:00510178	Lung	IAC	actin filament bundle assembly	40/2061	157/18723	2.66e-07	2.14e-05	40
GO:00329708	Lung	IAC	regulation of actin filament-based process	77/2061	397/18723	4.85e-07	3.10e-05	77
GO:00615728	Lung	IAC	actin filament bundle organization	40/2061	161/18723	5.43e-07	3.32e-05	40
GO:00329568	Lung	IAC	regulation of actin cytoskeleton organization	70/2061	358/18723	1.17e-06	6.20e-05	70
GO:19029038	Lung	IAC	regulation of supramolecular fiber organization	73/2061	383/18723	1.87e-06	8.87e-05	73
GO:00605624	Lung	IAC	epithelial tube morphogenesis	63/2061	325/18723	5.28e-06	2.07e-04	63
GO:00322318	Lung	IAC	regulation of actin filament bundle assembly	28/2061	105/18723	6.21e-06	2.30e-04	28
GO:00452168	Lung	IAC	cell-cell junction organization	43/2061	200/18723	1.21e-05	3.64e-04	43
GO:01100538	Lung	IAC	regulation of actin filament organization	54/2061	278/18723	2.27e-05	6.28e-04	54
GO:00439545	Lung	IAC	cellular component maintenance	17/2061	61/18723	2.24e-04	3.89e-03	17
GO:00016554	Lung	IAC	urogenital system development	59/2061	338/18723	2.27e-04	3.93e-03	59
GO:00343325	Lung	IAC	adherens junction organization	13/2061	49/18723	1.95e-03	1.97e-02	13
GO:00506735	Lung	IAC	epithelial cell proliferation	68/2061	437/18723	2.05e-03	2.05e-02	68
GO:00720014	Lung	IAC	renal system development	50/2061	302/18723	2.13e-03	2.11e-02	50
GO:00721604	Lung	IAC	nephron tubule epithelial cell differentiation	6/2061	14/18723	2.42e-03	2.33e-02	6
GO:00018223	Lung	IAC	kidney development	48/2061	293/18723	3.19e-03	2.77e-02	48
GO:00720734	Lung	IAC	kidney epithelium development	26/2061	136/18723	3.50e-03	2.96e-02	26

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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

MTSS1

SNV

Missense_Mutation

c.923C>G

p.Ser308Cys

p.S308C

O43312

protein_coding

tolerated(0.11)

probably_damaging(1)

TCGA-A2-A0YH-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

MTSS1

SNV

Missense_Mutation

c.294C>A

p.Ser98Arg

p.S98R

O43312

protein_coding

tolerated(0.06)

probably_damaging(0.988)

TCGA-A8-A07R-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Ancillary

zoledronic

MTSS1

SNV

Missense_Mutation

c.1084N>A

p.Glu362Lys

p.E362K

O43312

protein_coding

tolerated(0.46)

benign(0.182)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MTSS1

SNV

Missense_Mutation

rs762528178

c.1930N>T

p.Arg644Trp

p.R644W

O43312

protein_coding

tolerated(0.18)

possibly_damaging(0.84)

TCGA-AR-A1AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

MTSS1

SNV

Missense_Mutation

c.252G>A

p.Met84Ile

p.M84I

O43312

protein_coding

deleterious(0.03)

probably_damaging(0.993)

TCGA-AR-A250-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

MTSS1

SNV

Missense_Mutation

novel

c.1532N>T

p.Thr511Ile

p.T511I

O43312

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

MTSS1

SNV

Missense_Mutation

novel

c.1268N>C

p.Asp423Ala

p.D423A

O43312

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-BH-A204-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MTSS1

SNV

Missense_Mutation

rs149780096

c.1395N>A

p.Met465Ile

p.M465I

O43312

protein_coding

tolerated(0.46)

benign(0.023)

TCGA-C8-A12T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MTSS1

SNV

Missense_Mutation

novel

c.421N>G

p.Ser141Ala

p.S141A

O43312

protein_coding

deleterious(0.01)

probably_damaging(0.998)

TCGA-S3-AA11-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

letrozole

MTSS1

insertion

Nonsense_Mutation

novel

c.1292_1293insAAAAAATAATAATAAATAAA

p.Arg432LysfsTer6

p.R432Kfs*6

O43312

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

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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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