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: STOML2

Gene summary for STOML2

Gene summary.

Gene information	Species	Human
	Gene symbol	STOML2
	Gene ID	30968
	Gene name	stomatin like 2
	Gene Alias	HSPC108
	Cytomap	9p13.3
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	Q9UJZ1

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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
30968	STOML2	GSM4909281	Human	Breast	IDC	4.34e-09	3.78e-01	0.21
30968	STOML2	GSM4909282	Human	Breast	IDC	1.61e-38	6.86e-01	-0.0288
30968	STOML2	GSM4909285	Human	Breast	IDC	6.64e-19	4.19e-01	0.21
30968	STOML2	GSM4909288	Human	Breast	IDC	3.62e-09	4.12e-01	0.0988
30968	STOML2	GSM4909290	Human	Breast	IDC	2.28e-09	4.83e-01	0.2096
30968	STOML2	GSM4909292	Human	Breast	IDC	6.33e-10	7.66e-01	0.1236
30968	STOML2	GSM4909293	Human	Breast	IDC	5.19e-04	2.61e-01	0.1581
30968	STOML2	GSM4909296	Human	Breast	IDC	7.03e-11	8.27e-02	0.1524
30968	STOML2	GSM4909297	Human	Breast	IDC	1.70e-14	-7.85e-02	0.1517
30968	STOML2	GSM4909304	Human	Breast	IDC	3.72e-07	3.50e-01	0.1636
30968	STOML2	GSM4909311	Human	Breast	IDC	2.73e-25	-2.03e-01	0.1534
30968	STOML2	GSM4909312	Human	Breast	IDC	1.40e-08	5.91e-02	0.1552
30968	STOML2	GSM4909316	Human	Breast	IDC	3.61e-04	2.39e-03	0.21
30968	STOML2	GSM4909319	Human	Breast	IDC	3.17e-39	-8.15e-02	0.1563
30968	STOML2	GSM4909320	Human	Breast	IDC	4.24e-07	-3.95e-03	0.1575
30968	STOML2	GSM4909321	Human	Breast	IDC	3.41e-12	-8.52e-02	0.1559
30968	STOML2	brca1	Human	Breast	Precancer	9.20e-09	3.94e-01	-0.0338
30968	STOML2	brca2	Human	Breast	Precancer	3.19e-05	2.65e-01	-0.024
30968	STOML2	brca3	Human	Breast	Precancer	6.80e-04	2.79e-01	-0.0263
30968	STOML2	NCCBC14	Human	Breast	DCIS	3.36e-06	-1.56e-01	0.2021

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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
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:00460349	Breast	Precancer	ATP metabolic process	82/1080	277/18723	1.94e-36	5.19e-33	82
GO:00061199	Breast	Precancer	oxidative phosphorylation	53/1080	141/18723	1.15e-29	2.04e-26	53
GO:00090608	Breast	Precancer	aerobic respiration	58/1080	189/18723	5.69e-27	7.62e-24	58
GO:00060918	Breast	Precancer	generation of precursor metabolites and energy	94/1080	490/18723	1.54e-25	1.64e-22	94
GO:00453338	Breast	Precancer	cellular respiration	59/1080	230/18723	5.97e-23	5.32e-20	59
GO:00159808	Breast	Precancer	energy derivation by oxidation of organic compounds	70/1080	318/18723	8.33e-23	6.37e-20	70
GO:19026008	Breast	Precancer	proton transmembrane transport	39/1080	157/18723	4.18e-15	1.18e-12	39
GO:00159857	Breast	Precancer	energy coupled proton transport, down electrochemical gradient	16/1080	26/18723	4.15e-14	9.65e-12	16
GO:00159867	Breast	Precancer	ATP synthesis coupled proton transport	16/1080	26/18723	4.15e-14	9.65e-12	16
GO:00427766	Breast	Precancer	mitochondrial ATP synthesis coupled proton transport	13/1080	19/18723	1.43e-12	2.74e-10	13
GO:00067547	Breast	Precancer	ATP biosynthetic process	21/1080	57/18723	2.31e-12	4.26e-10	21
GO:00068398	Breast	Precancer	mitochondrial transport	45/1080	254/18723	1.37e-11	1.88e-09	45
GO:00092067	Breast	Precancer	purine ribonucleoside triphosphate biosynthetic process	22/1080	68/18723	1.41e-11	1.88e-09	22
GO:00091457	Breast	Precancer	purine nucleoside triphosphate biosynthetic process	22/1080	69/18723	1.95e-11	2.43e-09	22
GO:00092017	Breast	Precancer	ribonucleoside triphosphate biosynthetic process	22/1080	74/18723	9.18e-11	1.00e-08	22
GO:00091448	Breast	Precancer	purine nucleoside triphosphate metabolic process	24/1080	88/18723	9.66e-11	1.03e-08	24
GO:00092057	Breast	Precancer	purine ribonucleoside triphosphate metabolic process	23/1080	82/18723	1.27e-10	1.34e-08	23
GO:00091427	Breast	Precancer	nucleoside triphosphate biosynthetic process	23/1080	85/18723	2.82e-10	2.69e-08	23
GO:00091997	Breast	Precancer	ribonucleoside triphosphate metabolic process	23/1080	89/18723	7.65e-10	6.66e-08	23
GO:00091418	Breast	Precancer	nucleoside triphosphate metabolic process	26/1080	112/18723	7.72e-10	6.66e-08	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

STOML2

insertion

In_Frame_Ins

novel

c.869_870insTGGGGA

p.Ala290_Lys291insGlyAsp

p.A290_K291insGD

Q9UJZ1

protein_coding

TCGA-BH-A0H7-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

STOML2

insertion

In_Frame_Ins

novel

c.868_869insAGCTGGGCTTGGCCAGGGAGT

p.Ala290delinsGluLeuGlyLeuAlaArgGluSer

p.A290delinsELGLARES

Q9UJZ1

protein_coding

TCGA-BH-A0H7-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

STOML2

SNV

Missense_Mutation

rs763483882

c.215G>A

p.Arg72Gln

p.R72Q

Q9UJZ1

protein_coding

tolerated(0.09)

benign(0.094)

TCGA-EA-A3HS-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

STOML2

SNV

Missense_Mutation

rs753222022

c.511N>T

p.Arg171Cys

p.R171C

Q9UJZ1

protein_coding

deleterious(0.01)

possibly_damaging(0.892)

TCGA-AA-3966-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

STOML2

SNV

Missense_Mutation

rs201944176

c.776G>A

p.Arg259Gln

p.R259Q

Q9UJZ1

protein_coding

tolerated(0.48)

benign(0.003)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

STOML2

SNV

Missense_Mutation

c.1062G>T

p.Lys354Asn

p.K354N

Q9UJZ1

protein_coding

deleterious_low_confidence(0.01)

benign(0.003)

TCGA-G4-6303-01

Colorectum

colon adenocarcinoma

Female

<65

III/IV

Chemotherapy

5-fu

STOML2

SNV

Missense_Mutation

c.445N>A

p.Glu149Lys

p.E149K

Q9UJZ1

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-G4-6304-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Chemotherapy

fluorouracil

STOML2

SNV

Missense_Mutation

novel

c.628N>T

p.Thr210Ser

p.T210S

Q9UJZ1

protein_coding

tolerated(0.36)

benign(0.098)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

STOML2

SNV

Missense_Mutation

rs781632715

c.512N>A

p.Arg171His

p.R171H

Q9UJZ1

protein_coding

tolerated(0.1)

possibly_damaging(0.806)

TCGA-AJ-A3EK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

STOML2

SNV

Missense_Mutation

rs201944176

c.776N>A

p.Arg259Gln

p.R259Q

Q9UJZ1

protein_coding

tolerated(0.48)

benign(0.003)

TCGA-AJ-A5DW-01

Endometrium

uterine corpus endometrioid carcinoma

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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