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: TMEM109

Gene summary for TMEM109

Gene summary.

Gene information	Species	Human
	Gene symbol	TMEM109
	Gene ID	79073
	Gene name	transmembrane protein 109
	Gene Alias	TMEM109
	Cytomap	11q12.2
	Gene Type	protein-coding
	GO ID	GO:0006810
	UniProtAcc	Q9BVC6

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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
79073	TMEM109	LZE2T	Human	Esophagus	ESCC	3.00e-03	9.12e-01	0.082
79073	TMEM109	LZE3D	Human	Esophagus	HGIN	4.48e-02	4.91e-01	0.0668
79073	TMEM109	LZE4T	Human	Esophagus	ESCC	1.83e-15	6.36e-01	0.0811
79073	TMEM109	LZE7T	Human	Esophagus	ESCC	2.58e-02	4.18e-01	0.0667
79073	TMEM109	LZE8T	Human	Esophagus	ESCC	3.08e-04	2.47e-01	0.067
79073	TMEM109	LZE20T	Human	Esophagus	ESCC	6.89e-03	8.41e-02	0.0662
79073	TMEM109	LZE24T	Human	Esophagus	ESCC	1.68e-17	6.59e-01	0.0596
79073	TMEM109	LZE22D3	Human	Esophagus	HGIN	4.25e-02	2.53e-01	0.0653
79073	TMEM109	LZE21T	Human	Esophagus	ESCC	7.13e-04	1.78e-01	0.0655
79073	TMEM109	LZE6T	Human	Esophagus	ESCC	9.77e-10	3.16e-01	0.0845
79073	TMEM109	P1T-E	Human	Esophagus	ESCC	1.49e-07	4.96e-01	0.0875
79073	TMEM109	P2T-E	Human	Esophagus	ESCC	2.21e-32	6.88e-01	0.1177
79073	TMEM109	P4T-E	Human	Esophagus	ESCC	1.90e-39	1.12e+00	0.1323
79073	TMEM109	P5T-E	Human	Esophagus	ESCC	6.11e-39	8.55e-01	0.1327
79073	TMEM109	P8T-E	Human	Esophagus	ESCC	1.54e-37	8.53e-01	0.0889
79073	TMEM109	P9T-E	Human	Esophagus	ESCC	3.54e-28	6.80e-01	0.1131
79073	TMEM109	P10T-E	Human	Esophagus	ESCC	4.01e-41	7.93e-01	0.116
79073	TMEM109	P11T-E	Human	Esophagus	ESCC	1.92e-28	1.23e+00	0.1426
79073	TMEM109	P12T-E	Human	Esophagus	ESCC	1.90e-49	9.36e-01	0.1122
79073	TMEM109	P15T-E	Human	Esophagus	ESCC	8.36e-33	9.21e-01	0.1149

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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
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:009719327	Esophagus	HGIN	intrinsic apoptotic signaling pathway	90/2587	288/18723	1.50e-14	2.80e-12	90
GO:007233127	Esophagus	HGIN	signal transduction by p53 class mediator	49/2587	163/18723	5.71e-08	3.06e-06	49
GO:007233220	Esophagus	HGIN	intrinsic apoptotic signaling pathway by p53 class mediator	26/2587	76/18723	5.43e-06	1.73e-04	26
GO:000863020	Esophagus	HGIN	intrinsic apoptotic signaling pathway in response to DNA damage	28/2587	99/18723	1.24e-04	2.54e-03	28
GO:004277120	Esophagus	HGIN	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	15/2587	43/18723	4.06e-04	6.15e-03	15
GO:007147919	Esophagus	HGIN	cellular response to ionizing radiation	21/2587	72/18723	5.31e-04	7.59e-03	21
GO:000931418	Esophagus	HGIN	response to radiation	88/2587	456/18723	6.26e-04	8.65e-03	88
GO:00714789	Esophagus	HGIN	cellular response to radiation	42/2587	186/18723	7.66e-04	1.00e-02	42
GO:007121418	Esophagus	HGIN	cellular response to abiotic stimulus	66/2587	331/18723	1.21e-03	1.45e-02	66
GO:010400418	Esophagus	HGIN	cellular response to environmental stimulus	66/2587	331/18723	1.21e-03	1.45e-02	66
GO:00103327	Esophagus	HGIN	response to gamma radiation	16/2587	56/18723	2.96e-03	2.86e-02	16
GO:00102129	Esophagus	HGIN	response to ionizing radiation	33/2587	148/18723	3.28e-03	3.10e-02	33
GO:0097193111	Esophagus	ESCC	intrinsic apoptotic signaling pathway	222/8552	288/18723	5.87e-28	2.02e-25	222
GO:0072331111	Esophagus	ESCC	signal transduction by p53 class mediator	121/8552	163/18723	9.61e-14	4.69e-12	121
GO:001021217	Esophagus	ESCC	response to ionizing radiation	110/8552	148/18723	1.11e-12	4.78e-11	110
GO:0008630110	Esophagus	ESCC	intrinsic apoptotic signaling pathway in response to DNA damage	78/8552	99/18723	1.43e-11	5.08e-10	78
GO:000931419	Esophagus	ESCC	response to radiation	277/8552	456/18723	4.42e-11	1.43e-09	277
GO:007121419	Esophagus	ESCC	cellular response to abiotic stimulus	206/8552	331/18723	7.52e-10	1.88e-08	206
GO:010400419	Esophagus	ESCC	cellular response to environmental stimulus	206/8552	331/18723	7.52e-10	1.88e-08	206
GO:0042771110	Esophagus	ESCC	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	38/8552	43/18723	5.75e-09	1.18e-07	38

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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

TMEM109

insertion

Nonsense_Mutation

novel

c.531_532insCAGGAAGGAGAGACAGCCTGTTGGCCATCCCTGTAGAC

p.Ser178GlnfsTer12

p.S178Qfs*12

Q9BVC6

protein_coding

TCGA-B6-A0I8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TMEM109

insertion

Frame_Shift_Ins

novel

c.98_99insGG

p.Gln34AlafsTer22

p.Q34Afs*22

Q9BVC6

protein_coding

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

TMEM109

insertion

Frame_Shift_Ins

novel

c.99_100insAGACAGCCACTGGAGAGTTGGGGCTGGCACAGAA

p.Gln34ArgfsTer30

p.Q34Rfs*30

Q9BVC6

protein_coding

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

TMEM109

insertion

Nonsense_Mutation

novel

c.136_137insGGGTCATCCTATGGCAGAAGGCAGAACCCAGCACATG

p.Lys46ArgfsTer13

p.K46Rfs*13

Q9BVC6

protein_coding

TCGA-BH-A0DS-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

cyclophosphamide

TMEM109

deletion

Frame_Shift_Del

novel

c.29delN

p.Gly11GlufsTer9

p.G11Efs*9

Q9BVC6

protein_coding

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

TMEM109

SNV

Missense_Mutation

c.690N>T

p.Gln230His

p.Q230H

Q9BVC6

protein_coding

deleterious(0)

possibly_damaging(0.81)

TCGA-A6-5665-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

TMEM109

SNV

Missense_Mutation

novel

c.553C>T

p.Arg185Trp

p.R185W

Q9BVC6

protein_coding

deleterious(0)

benign(0.023)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

TMEM109

SNV

Missense_Mutation

c.298T>C

p.Ser100Pro

p.S100P

Q9BVC6

protein_coding

tolerated(0.23)

probably_damaging(0.992)

TCGA-AY-6196-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Unknown

TMEM109

SNV

Missense_Mutation

novel

c.50C>T

p.Ala17Val

p.A17V

Q9BVC6

protein_coding

tolerated_low_confidence(0.7)

benign(0.001)

TCGA-AZ-4315-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Unknown

TMEM109

SNV

Missense_Mutation

rs753654818

c.310N>A

p.Ala104Thr

p.A104T

Q9BVC6

protein_coding

deleterious(0.04)

benign(0.029)

TCGA-F4-6856-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Ancillary

leucovorin

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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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