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: TMEM126B

Gene summary for TMEM126B

Gene summary.

Gene information	Species	Human
	Gene symbol	TMEM126B
	Gene ID	55863
	Gene name	transmembrane protein 126B
	Gene Alias	HT007
	Cytomap	11q14.1
	Gene Type	protein-coding
	GO ID	GO:0006996
	UniProtAcc	A0A024R5L4

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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
55863	TMEM126B	LZE2T	Human	Esophagus	ESCC	2.39e-04	6.06e-01	0.082
55863	TMEM126B	LZE4T	Human	Esophagus	ESCC	1.32e-03	1.53e-01	0.0811
55863	TMEM126B	LZE7T	Human	Esophagus	ESCC	1.55e-05	3.11e-01	0.0667
55863	TMEM126B	LZE20T	Human	Esophagus	ESCC	1.83e-02	1.62e-01	0.0662
55863	TMEM126B	LZE22T	Human	Esophagus	ESCC	5.52e-03	2.74e-01	0.068
55863	TMEM126B	LZE24T	Human	Esophagus	ESCC	5.30e-22	7.04e-01	0.0596
55863	TMEM126B	LZE6T	Human	Esophagus	ESCC	3.99e-03	1.93e-01	0.0845
55863	TMEM126B	P1T-E	Human	Esophagus	ESCC	7.61e-04	2.59e-01	0.0875
55863	TMEM126B	P2T-E	Human	Esophagus	ESCC	2.62e-17	1.81e-01	0.1177
55863	TMEM126B	P4T-E	Human	Esophagus	ESCC	1.24e-44	9.37e-01	0.1323
55863	TMEM126B	P5T-E	Human	Esophagus	ESCC	1.35e-17	3.91e-01	0.1327
55863	TMEM126B	P8T-E	Human	Esophagus	ESCC	4.53e-15	2.11e-01	0.0889
55863	TMEM126B	P9T-E	Human	Esophagus	ESCC	9.16e-22	4.58e-01	0.1131
55863	TMEM126B	P10T-E	Human	Esophagus	ESCC	2.03e-15	3.47e-01	0.116
55863	TMEM126B	P11T-E	Human	Esophagus	ESCC	1.22e-19	7.09e-01	0.1426
55863	TMEM126B	P12T-E	Human	Esophagus	ESCC	1.14e-18	4.28e-01	0.1122
55863	TMEM126B	P15T-E	Human	Esophagus	ESCC	1.06e-10	1.96e-01	0.1149
55863	TMEM126B	P16T-E	Human	Esophagus	ESCC	6.47e-12	2.21e-01	0.1153
55863	TMEM126B	P17T-E	Human	Esophagus	ESCC	1.08e-13	5.45e-01	0.1278
55863	TMEM126B	P19T-E	Human	Esophagus	ESCC	2.21e-14	8.10e-01	0.1662

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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:0033108110	Esophagus	ESCC	mitochondrial respiratory chain complex assembly	83/8552	93/18723	9.56e-19	1.05e-16	83
GO:0010257110	Esophagus	ESCC	NADH dehydrogenase complex assembly	50/8552	57/18723	3.78e-11	1.24e-09	50
GO:0032981110	Esophagus	ESCC	mitochondrial respiratory chain complex I assembly	50/8552	57/18723	3.78e-11	1.24e-09	50
GO:00331087	Liver	Cirrhotic	mitochondrial respiratory chain complex assembly	64/4634	93/18723	3.85e-19	7.79e-17	64
GO:00102577	Liver	Cirrhotic	NADH dehydrogenase complex assembly	42/4634	57/18723	1.06e-14	1.06e-12	42
GO:00329817	Liver	Cirrhotic	mitochondrial respiratory chain complex I assembly	42/4634	57/18723	1.06e-14	1.06e-12	42
GO:003310812	Liver	HCC	mitochondrial respiratory chain complex assembly	80/7958	93/18723	3.47e-18	4.15e-16	80
GO:001025712	Liver	HCC	NADH dehydrogenase complex assembly	50/7958	57/18723	1.50e-12	7.20e-11	50
GO:003298112	Liver	HCC	mitochondrial respiratory chain complex I assembly	50/7958	57/18723	1.50e-12	7.20e-11	50
GO:003310818	Oral cavity	OSCC	mitochondrial respiratory chain complex assembly	75/7305	93/18723	2.17e-16	1.68e-14	75
GO:001025718	Oral cavity	OSCC	NADH dehydrogenase complex assembly	45/7305	57/18723	8.53e-10	2.13e-08	45
GO:003298118	Oral cavity	OSCC	mitochondrial respiratory chain complex I assembly	45/7305	57/18723	8.53e-10	2.13e-08	45
GO:003310819	Oral cavity	LP	mitochondrial respiratory chain complex assembly	63/4623	93/18723	2.24e-18	4.13e-16	63
GO:001025719	Oral cavity	LP	NADH dehydrogenase complex assembly	41/4623	57/18723	7.93e-14	7.89e-12	41
GO:003298119	Oral cavity	LP	mitochondrial respiratory chain complex I assembly	41/4623	57/18723	7.93e-14	7.89e-12	41
GO:003310824	Skin	cSCC	mitochondrial respiratory chain complex assembly	64/4864	93/18723	5.48e-18	6.58e-16	64
GO:001025724	Skin	cSCC	NADH dehydrogenase complex assembly	42/4864	57/18723	6.46e-14	4.09e-12	42
GO:003298124	Skin	cSCC	mitochondrial respiratory chain complex I assembly	42/4864	57/18723	6.46e-14	4.09e-12	42
GO:0033108111	Thyroid	PTC	mitochondrial respiratory chain complex assembly	65/5968	93/18723	5.60e-14	3.21e-12	65
GO:0010257111	Thyroid	PTC	NADH dehydrogenase complex assembly	43/5968	57/18723	1.73e-11	6.81e-10	43

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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

TMEM126B

SNV

Missense_Mutation

novel

c.264N>A

p.Phe88Leu

p.F88L

Q8IUX1

protein_coding

tolerated(1)

benign(0.001)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TMEM126B

insertion

Frame_Shift_Ins

novel

c.172_173insA

p.Asn60LysfsTer3

p.N60Kfs*3

Q8IUX1

protein_coding

TCGA-AA-3492-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

TMEM126B

SNV

Missense_Mutation

rs773475165

c.520N>A

p.Val174Ile

p.V174I

Q8IUX1

protein_coding

tolerated(0.08)

benign(0.101)

TCGA-AP-A05O-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Chemotherapy

carboplatin

TMEM126B

SNV

Missense_Mutation

novel

c.190N>A

p.Leu64Ile

p.L64I

Q8IUX1

protein_coding

deleterious(0.02)

possibly_damaging(0.749)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

TMEM126B

SNV

Missense_Mutation

novel

c.180T>G

p.Asn60Lys

p.N60K

Q8IUX1

protein_coding

tolerated(1)

benign(0)

TCGA-B5-A1MR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

TMEM126B

SNV

Missense_Mutation

novel

c.386N>T

p.Ala129Val

p.A129V

Q8IUX1

protein_coding

tolerated(0.08)

benign(0.305)

TCGA-B5-A3FC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

TMEM126B

SNV

Missense_Mutation

c.182N>G

p.Phe61Cys

p.F61C

Q8IUX1

protein_coding

deleterious(0.01)

possibly_damaging(0.819)

TCGA-BS-A0UV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

TMEM126B

SNV

Missense_Mutation

c.523N>T

p.Pro175Ser

p.P175S

Q8IUX1

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-BS-A0UV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

TMEM126B

SNV

Missense_Mutation

novel

c.473N>A

p.Ser158Tyr

p.S158Y

Q8IUX1

protein_coding

deleterious(0.03)

possibly_damaging(0.472)

TCGA-E6-A1LX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

TMEM126B

SNV

Missense_Mutation

novel

c.473N>A

p.Ser158Tyr

p.S158Y

Q8IUX1

protein_coding

deleterious(0.03)

possibly_damaging(0.472)

TCGA-EY-A1GI-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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