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: TMEM9

Gene summary for TMEM9

Gene summary.

Gene information	Species	Human
	Gene symbol	TMEM9
	Gene ID	252839
	Gene name	transmembrane protein 9
	Gene Alias	DERM4
	Cytomap	1q32.1
	Gene Type	protein-coding
	GO ID	GO:0006807
	UniProtAcc	A0A024R967

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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
252839	TMEM9	P52T-E	Human	Esophagus	ESCC	1.04e-47	1.16e+00	0.1555
252839	TMEM9	P54T-E	Human	Esophagus	ESCC	3.90e-30	5.84e-01	0.0975
252839	TMEM9	P56T-E	Human	Esophagus	ESCC	1.83e-17	2.33e+00	0.1613
252839	TMEM9	P57T-E	Human	Esophagus	ESCC	5.25e-38	8.56e-01	0.0926
252839	TMEM9	P61T-E	Human	Esophagus	ESCC	1.03e-34	1.13e+00	0.099
252839	TMEM9	P62T-E	Human	Esophagus	ESCC	2.83e-76	1.35e+00	0.1302
252839	TMEM9	P65T-E	Human	Esophagus	ESCC	1.21e-36	9.29e-01	0.0978
252839	TMEM9	P74T-E	Human	Esophagus	ESCC	1.00e-47	1.44e+00	0.1479
252839	TMEM9	P75T-E	Human	Esophagus	ESCC	6.18e-45	9.27e-01	0.1125
252839	TMEM9	P76T-E	Human	Esophagus	ESCC	3.17e-75	1.52e+00	0.1207
252839	TMEM9	P79T-E	Human	Esophagus	ESCC	1.00e-78	1.35e+00	0.1154
252839	TMEM9	P80T-E	Human	Esophagus	ESCC	4.09e-47	1.34e+00	0.155
252839	TMEM9	P82T-E	Human	Esophagus	ESCC	2.09e-20	1.32e+00	0.1072
252839	TMEM9	P83T-E	Human	Esophagus	ESCC	2.16e-44	1.33e+00	0.1738
252839	TMEM9	P84T-E	Human	Esophagus	ESCC	2.67e-08	6.54e-01	0.0933
252839	TMEM9	P89T-E	Human	Esophagus	ESCC	3.62e-29	2.15e+00	0.1752
252839	TMEM9	P91T-E	Human	Esophagus	ESCC	9.61e-26	2.58e+00	0.1828
252839	TMEM9	P107T-E	Human	Esophagus	ESCC	5.73e-34	9.14e-01	0.171
252839	TMEM9	P126T-E	Human	Esophagus	ESCC	1.13e-05	7.21e-01	0.1125
252839	TMEM9	P127T-E	Human	Esophagus	ESCC	6.07e-24	2.71e-01	0.0826

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:00072496	Breast	Precancer	I-kappaB kinase/NF-kappaB signaling	27/1080	281/18723	6.58e-03	4.53e-02	27
GO:00431227	Breast	IDC	regulation of I-kappaB kinase/NF-kappaB signaling	34/1434	249/18723	7.18e-04	8.77e-03	34
GO:000724914	Breast	IDC	I-kappaB kinase/NF-kappaB signaling	37/1434	281/18723	8.58e-04	9.98e-03	37
GO:00431236	Breast	IDC	positive regulation of I-kappaB kinase/NF-kappaB signaling	26/1434	186/18723	2.06e-03	1.95e-02	26
GO:004312214	Breast	DCIS	regulation of I-kappaB kinase/NF-kappaB signaling	32/1390	249/18723	1.67e-03	1.66e-02	32
GO:000724923	Breast	DCIS	I-kappaB kinase/NF-kappaB signaling	35/1390	281/18723	1.80e-03	1.74e-02	35
GO:004312313	Breast	DCIS	positive regulation of I-kappaB kinase/NF-kappaB signaling	24/1390	186/18723	5.66e-03	4.09e-02	24
GO:0042176	Colorectum	AD	regulation of protein catabolic process	160/3918	391/18723	1.06e-19	7.34e-17	160
GO:0016050	Colorectum	AD	vesicle organization	101/3918	300/18723	1.65e-07	7.17e-06	101
GO:1900180	Colorectum	AD	regulation of protein localization to nucleus	55/3918	136/18723	1.70e-07	7.34e-06	55
GO:0034504	Colorectum	AD	protein localization to nucleus	94/3918	290/18723	2.83e-06	8.09e-05	94
GO:0030111	Colorectum	AD	regulation of Wnt signaling pathway	102/3918	328/18723	8.51e-06	2.03e-04	102
GO:0016055	Colorectum	AD	Wnt signaling pathway	130/3918	444/18723	1.60e-05	3.37e-04	130
GO:0198738	Colorectum	AD	cell-cell signaling by wnt	130/3918	446/18723	2.02e-05	4.10e-04	130
GO:0045861	Colorectum	AD	negative regulation of proteolysis	106/3918	351/18723	2.33e-05	4.57e-04	106
GO:0007032	Colorectum	AD	endosome organization	33/3918	82/18723	5.30e-05	9.01e-04	33
GO:0060070	Colorectum	AD	canonical Wnt signaling pathway	90/3918	303/18723	1.76e-04	2.38e-03	90
GO:0043123	Colorectum	AD	positive regulation of I-kappaB kinase/NF-kappaB signaling	60/3918	186/18723	1.91e-04	2.56e-03	60
GO:0043122	Colorectum	AD	regulation of I-kappaB kinase/NF-kappaB signaling	76/3918	249/18723	2.17e-04	2.85e-03	76
GO:0060828	Colorectum	AD	regulation of canonical Wnt signaling pathway	77/3918	253/18723	2.19e-04	2.87e-03	77

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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

TMEM9

SNV

Missense_Mutation

c.377C>G

p.Thr126Ser

p.T126S

protein_coding

tolerated(1)

benign(0.427)

TCGA-AN-A0FX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TMEM9

SNV

Missense_Mutation

rs776119463

c.529A>G

p.Thr177Ala

p.T177A

protein_coding

deleterious(0.04)

probably_damaging(0.983)

TCGA-CK-5914-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Unknown

TMEM9

SNV

Missense_Mutation

novel

c.458N>A

p.Ala153Glu

p.A153E

protein_coding

deleterious(0.01)

possibly_damaging(0.798)

TCGA-G4-6320-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Chemotherapy

oxaliplatin

TMEM9

SNV

Missense_Mutation

novel

c.532G>T

p.Val178Phe

p.V178F

protein_coding

deleterious(0)

probably_damaging(0.997)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

TMEM9

SNV

Missense_Mutation

novel

c.181G>A

p.Val61Met

p.V61M

protein_coding

deleterious(0.04)

possibly_damaging(0.554)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

TMEM9

SNV

Missense_Mutation

c.538G>A

p.Asp180Asn

p.D180N

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

TMEM9

SNV

Missense_Mutation

rs746735599

c.452C>T

p.Pro151Leu

p.P151L

protein_coding

deleterious(0.04)

benign(0.017)

TCGA-B5-A11H-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Hormone Therapy

megace

TMEM9

SNV

Missense_Mutation

novel

c.238N>A

p.Glu80Lys

p.E80K

protein_coding

tolerated(0.07)

probably_damaging(0.993)

TCGA-B5-A3FA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

TMEM9

SNV

Missense_Mutation

novel

c.519G>T

p.Glu173Asp

p.E173D

protein_coding

deleterious(0)

probably_damaging(0.983)

TCGA-BG-A3EW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

TMEM9

SNV

Missense_Mutation

c.5N>T

p.Lys2Met

p.K2M

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.984)

TCGA-D1-A15X-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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