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: TMEM11

Gene summary for TMEM11

Gene summary.

Gene information	Species	Human
	Gene symbol	TMEM11
	Gene ID	8834
	Gene name	transmembrane protein 11
	Gene Alias	C17orf35
	Cytomap	17p11.2
	Gene Type	protein-coding
	GO ID	GO:0006996
	UniProtAcc	P17152

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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
8834	TMEM11	LZE4T	Human	Esophagus	ESCC	5.79e-09	4.71e-01	0.0811
8834	TMEM11	LZE7T	Human	Esophagus	ESCC	2.77e-10	6.55e-01	0.0667
8834	TMEM11	LZE8T	Human	Esophagus	ESCC	5.20e-07	2.10e-01	0.067
8834	TMEM11	LZE20T	Human	Esophagus	ESCC	1.61e-07	1.85e-01	0.0662
8834	TMEM11	LZE22T	Human	Esophagus	ESCC	5.01e-04	4.41e-01	0.068
8834	TMEM11	LZE24T	Human	Esophagus	ESCC	7.06e-23	7.44e-01	0.0596
8834	TMEM11	LZE21T	Human	Esophagus	ESCC	3.24e-03	2.41e-01	0.0655
8834	TMEM11	LZE6T	Human	Esophagus	ESCC	3.29e-04	4.00e-01	0.0845
8834	TMEM11	P1T-E	Human	Esophagus	ESCC	5.54e-11	5.44e-01	0.0875
8834	TMEM11	P2T-E	Human	Esophagus	ESCC	1.25e-31	6.35e-01	0.1177
8834	TMEM11	P4T-E	Human	Esophagus	ESCC	7.67e-39	1.10e+00	0.1323
8834	TMEM11	P5T-E	Human	Esophagus	ESCC	5.73e-23	3.76e-01	0.1327
8834	TMEM11	P8T-E	Human	Esophagus	ESCC	6.07e-37	8.12e-01	0.0889
8834	TMEM11	P9T-E	Human	Esophagus	ESCC	6.56e-24	4.89e-01	0.1131
8834	TMEM11	P10T-E	Human	Esophagus	ESCC	8.72e-30	5.41e-01	0.116
8834	TMEM11	P11T-E	Human	Esophagus	ESCC	5.55e-20	8.67e-01	0.1426
8834	TMEM11	P12T-E	Human	Esophagus	ESCC	7.49e-33	6.47e-01	0.1122
8834	TMEM11	P15T-E	Human	Esophagus	ESCC	2.05e-24	3.68e-01	0.1149
8834	TMEM11	P16T-E	Human	Esophagus	ESCC	1.42e-37	7.39e-01	0.1153
8834	TMEM11	P17T-E	Human	Esophagus	ESCC	5.76e-13	5.25e-01	0.1278

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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:009719310	Cervix	CC	intrinsic apoptotic signaling pathway	85/2311	288/18723	4.56e-15	6.46e-12	85
GO:003497610	Cervix	CC	response to endoplasmic reticulum stress	57/2311	256/18723	5.81e-06	1.42e-04	57
GO:00700599	Cervix	CC	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	21/2311	63/18723	1.18e-05	2.51e-04	21
GO:0097193	Colorectum	AD	intrinsic apoptotic signaling pathway	108/3918	288/18723	6.25e-11	6.41e-09	108
GO:0034976	Colorectum	AD	response to endoplasmic reticulum stress	90/3918	256/18723	8.48e-08	4.28e-06	90
GO:0070059	Colorectum	AD	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	29/3918	63/18723	7.03e-06	1.73e-04	29
GO:00971931	Colorectum	SER	intrinsic apoptotic signaling pathway	87/2897	288/18723	1.67e-10	2.32e-08	87
GO:00349761	Colorectum	SER	response to endoplasmic reticulum stress	74/2897	256/18723	3.01e-08	2.05e-06	74
GO:00700591	Colorectum	SER	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	25/2897	63/18723	2.92e-06	1.18e-04	25
GO:00971932	Colorectum	MSS	intrinsic apoptotic signaling pathway	102/3467	288/18723	6.06e-12	9.82e-10	102
GO:00349762	Colorectum	MSS	response to endoplasmic reticulum stress	81/3467	256/18723	2.65e-07	1.10e-05	81
GO:00700592	Colorectum	MSS	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	27/3467	63/18723	6.93e-06	1.79e-04	27
GO:00349764	Colorectum	FAP	response to endoplasmic reticulum stress	61/2622	256/18723	1.58e-05	4.10e-04	61
GO:00971934	Colorectum	FAP	intrinsic apoptotic signaling pathway	66/2622	288/18723	2.76e-05	6.33e-04	66
GO:00700593	Colorectum	FAP	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	18/2622	63/18723	1.95e-03	1.65e-02	18
GO:00971935	Colorectum	CRC	intrinsic apoptotic signaling pathway	57/2078	288/18723	9.77e-06	3.31e-04	57
GO:009719316	Endometrium	AEH	intrinsic apoptotic signaling pathway	75/2100	288/18723	1.46e-12	2.83e-10	75
GO:003497616	Endometrium	AEH	response to endoplasmic reticulum stress	62/2100	256/18723	2.88e-09	2.13e-07	62
GO:007005910	Endometrium	AEH	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	18/2100	63/18723	1.32e-04	1.80e-03	18
GO:009719317	Endometrium	EEC	intrinsic apoptotic signaling pathway	80/2168	288/18723	3.35e-14	9.13e-12	80

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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

TMEM11

insertion

Frame_Shift_Ins

novel

c.105_106insACAAGAGACAACAGAG

p.Tyr36ThrfsTer16

p.Y36Tfs*16

P17152

protein_coding

TCGA-A2-A0D4-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

TMEM11

SNV

Missense_Mutation

rs775552645

c.562N>A

p.Glu188Lys

p.E188K

P17152

protein_coding

tolerated(0.09)

benign(0.009)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

TMEM11

SNV

Missense_Mutation

rs775552645

c.562N>A

p.Glu188Lys

p.E188K

P17152

protein_coding

tolerated(0.09)

benign(0.009)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

TMEM11

SNV

Missense_Mutation

c.433N>T

p.Arg145Cys

p.R145C

P17152

protein_coding

deleterious(0)

possibly_damaging(0.712)

TCGA-F5-6814-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

TMEM11

SNV

Missense_Mutation

novel

c.102N>T

p.Glu34Asp

p.E34D

P17152

protein_coding

deleterious(0.01)

benign(0.162)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

TMEM11

SNV

Missense_Mutation

novel

c.217C>T

p.Arg73Cys

p.R73C

P17152

protein_coding

deleterious(0)

benign(0.226)

TCGA-AJ-A3OJ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

TMEM11

SNV

Missense_Mutation

rs775552645

c.562N>A

p.Glu188Lys

p.E188K

P17152

protein_coding

tolerated(0.09)

benign(0.009)

TCGA-AX-A05Z-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

TMEM11

SNV

Missense_Mutation

rs541612728

c.574G>A

p.Val192Ile

p.V192I

P17152

protein_coding

tolerated_low_confidence(0.08)

possibly_damaging(0.899)

TCGA-AX-A06F-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

TMEM11

SNV

Missense_Mutation

c.433N>T

p.Arg145Cys

p.R145C

P17152

protein_coding

deleterious(0)

possibly_damaging(0.712)

TCGA-AX-A0J1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

TMEM11

SNV

Missense_Mutation

rs527761394

c.532N>A

p.Ala178Thr

p.A178T

P17152

protein_coding

deleterious(0.03)

benign(0.258)

TCGA-B5-A11E-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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