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: TMED10

Gene summary for TMED10

Gene summary.

Gene information	Species	Human
	Gene symbol	TMED10
	Gene ID	10972
	Gene name	transmembrane p24 trafficking protein 10
	Gene Alias	P24(DELTA)
	Cytomap	14q24.3
	Gene Type	protein-coding
	GO ID	GO:0001655
	UniProtAcc	A0A024R6I3

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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
10972	TMED10	GSM4909280	Human	Breast	Precancer	1.30e-02	-5.23e-01	0.0305
10972	TMED10	GSM4909281	Human	Breast	IDC	2.39e-04	3.61e-01	0.21
10972	TMED10	GSM4909285	Human	Breast	IDC	1.82e-03	2.82e-01	0.21
10972	TMED10	GSM4909286	Human	Breast	IDC	1.07e-14	-4.48e-01	0.1081
10972	TMED10	GSM4909288	Human	Breast	IDC	3.38e-02	-9.03e-02	0.0988
10972	TMED10	GSM4909290	Human	Breast	IDC	1.86e-02	3.29e-01	0.2096
10972	TMED10	GSM4909293	Human	Breast	IDC	1.58e-05	3.03e-01	0.1581
10972	TMED10	GSM4909294	Human	Breast	IDC	2.92e-12	-3.87e-01	0.2022
10972	TMED10	GSM4909296	Human	Breast	IDC	4.56e-07	-8.91e-02	0.1524
10972	TMED10	GSM4909297	Human	Breast	IDC	1.16e-18	-2.73e-01	0.1517
10972	TMED10	GSM4909298	Human	Breast	IDC	1.36e-02	-1.39e-01	0.1551
10972	TMED10	GSM4909301	Human	Breast	IDC	4.75e-07	-3.03e-01	0.1577
10972	TMED10	GSM4909308	Human	Breast	IDC	5.64e-03	2.17e-01	0.158
10972	TMED10	GSM4909311	Human	Breast	IDC	1.64e-34	-3.48e-01	0.1534
10972	TMED10	GSM4909312	Human	Breast	IDC	2.64e-10	-1.21e-01	0.1552
10972	TMED10	GSM4909313	Human	Breast	IDC	8.57e-03	6.77e-02	0.0391
10972	TMED10	GSM4909319	Human	Breast	IDC	1.11e-52	-2.36e-01	0.1563
10972	TMED10	GSM4909320	Human	Breast	IDC	2.38e-10	-5.38e-01	0.1575
10972	TMED10	GSM4909321	Human	Breast	IDC	3.98e-15	-1.76e-01	0.1559
10972	TMED10	brca2	Human	Breast	Precancer	3.59e-11	4.24e-01	-0.024

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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
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:00525479	Breast	Precancer	regulation of peptidase activity	71/1080	461/18723	2.72e-14	6.94e-12	71
GO:00525489	Breast	Precancer	regulation of endopeptidase activity	67/1080	432/18723	1.06e-13	2.36e-11	67
GO:00458619	Breast	Precancer	negative regulation of proteolysis	50/1080	351/18723	2.99e-09	2.39e-07	50
GO:00513468	Breast	Precancer	negative regulation of hydrolase activity	50/1080	379/18723	3.85e-08	2.34e-06	50
GO:00104668	Breast	Precancer	negative regulation of peptidase activity	38/1080	262/18723	1.46e-07	7.82e-06	38
GO:00109519	Breast	Precancer	negative regulation of endopeptidase activity	37/1080	252/18723	1.55e-07	8.05e-06	37
GO:00018196	Breast	Precancer	positive regulation of cytokine production	52/1080	467/18723	4.18e-06	1.29e-04	52
GO:19049519	Breast	Precancer	positive regulation of establishment of protein localization	36/1080	319/18723	9.30e-05	1.75e-03	36
GO:00069009	Breast	Precancer	vesicle budding from membrane	12/1080	61/18723	1.61e-04	2.69e-03	12
GO:00512229	Breast	Precancer	positive regulation of protein transport	31/1080	303/18723	1.44e-03	1.50e-02	31
GO:00507086	Breast	Precancer	regulation of protein secretion	28/1080	268/18723	1.76e-03	1.74e-02	28
GO:00718064	Breast	Precancer	protein transmembrane transport	10/1080	59/18723	1.86e-03	1.81e-02	10
GO:0032732	Breast	Precancer	positive regulation of interleukin-1 production	11/1080	73/18723	2.96e-03	2.55e-02	11
GO:00716926	Breast	Precancer	protein localization to extracellular region	34/1080	368/18723	4.65e-03	3.58e-02	34
GO:00093067	Breast	Precancer	protein secretion	33/1080	359/18723	5.65e-03	4.08e-02	33
GO:00355927	Breast	Precancer	establishment of protein localization to extracellular region	33/1080	360/18723	5.89e-03	4.21e-02	33
GO:00481992	Breast	Precancer	vesicle targeting, to, from or within Golgi	5/1080	21/18723	5.93e-03	4.21e-02	5
GO:005254714	Breast	IDC	regulation of peptidase activity	96/1434	461/18723	7.58e-20	6.15e-17	96
GO:005254814	Breast	IDC	regulation of endopeptidase activity	88/1434	432/18723	1.20e-17	4.85e-15	88
GO:004586114	Breast	IDC	negative regulation of proteolysis	70/1434	351/18723	8.21e-14	2.22e-11	70

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0513018	Breast	Precancer	Pathogenic Escherichia coli infection	38/684	197/8465	3.12e-07	5.81e-06	4.45e-06	38
hsa0513019	Breast	Precancer	Pathogenic Escherichia coli infection	38/684	197/8465	3.12e-07	5.81e-06	4.45e-06	38
hsa0513024	Breast	IDC	Pathogenic Escherichia coli infection	42/867	197/8465	2.66e-06	3.92e-05	2.94e-05	42
hsa0513034	Breast	IDC	Pathogenic Escherichia coli infection	42/867	197/8465	2.66e-06	3.92e-05	2.94e-05	42
hsa0513043	Breast	DCIS	Pathogenic Escherichia coli infection	42/846	197/8465	1.40e-06	2.15e-05	1.59e-05	42
hsa0513053	Breast	DCIS	Pathogenic Escherichia coli infection	42/846	197/8465	1.40e-06	2.15e-05	1.59e-05	42
hsa0513020	Cervix	CC	Pathogenic Escherichia coli infection	63/1267	197/8465	9.28e-10	2.00e-08	1.19e-08	63
hsa05130110	Cervix	CC	Pathogenic Escherichia coli infection	63/1267	197/8465	9.28e-10	2.00e-08	1.19e-08	63
hsa0513044	Cervix	N_HPV	Pathogenic Escherichia coli infection	25/349	197/8465	4.71e-07	8.00e-06	6.25e-06	25
hsa0513054	Cervix	N_HPV	Pathogenic Escherichia coli infection	25/349	197/8465	4.71e-07	8.00e-06	6.25e-06	25
hsa05130	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa051301	Colorectum	AD	Pathogenic Escherichia coli infection	79/2092	197/8465	1.05e-06	1.36e-05	8.65e-06	79
hsa051302	Colorectum	SER	Pathogenic Escherichia coli infection	60/1580	197/8465	3.63e-05	4.31e-04	3.13e-04	60
hsa051303	Colorectum	SER	Pathogenic Escherichia coli infection	60/1580	197/8465	3.63e-05	4.31e-04	3.13e-04	60
hsa051304	Colorectum	MSS	Pathogenic Escherichia coli infection	73/1875	197/8465	1.10e-06	1.48e-05	9.06e-06	73
hsa051305	Colorectum	MSS	Pathogenic Escherichia coli infection	73/1875	197/8465	1.10e-06	1.48e-05	9.06e-06	73
hsa051306	Colorectum	MSI-H	Pathogenic Escherichia coli infection	31/797	197/8465	2.90e-03	2.93e-02	2.46e-02	31
hsa051307	Colorectum	MSI-H	Pathogenic Escherichia coli infection	31/797	197/8465	2.90e-03	2.93e-02	2.46e-02	31
hsa051308	Colorectum	FAP	Pathogenic Escherichia coli infection	62/1404	197/8465	1.37e-07	3.08e-06	1.87e-06	62
hsa051309	Colorectum	FAP	Pathogenic Escherichia coli infection	62/1404	197/8465	1.37e-07	3.08e-06	1.87e-06	62

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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

TMED10

SNV

Missense_Mutation

c.589C>G

p.Leu197Val

p.L197V

P49755

protein_coding

deleterious(0.01)

probably_damaging(0.986)

TCGA-C8-A12T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

TMED10

SNV

Missense_Mutation

novel

c.436N>G

p.Pro146Ala

p.P146A

P49755

protein_coding

deleterious(0.01)

probably_damaging(0.992)

TCGA-LL-A5YP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

TMED10

insertion

In_Frame_Ins

novel

c.239_240insATTACAAATGATGAACCTACA

p.Ala80_Gly81insLeuGlnMetMetAsnLeuHis

p.A80_G81insLQMMNLH

P49755

protein_coding

TCGA-AR-A0U0-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

TMED10

SNV

Missense_Mutation

novel

c.167N>A

p.Gly56Asp

p.G56D

P49755

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-A6-2672-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

TMED10

SNV

Missense_Mutation

rs767047055

c.117N>G

p.Asn39Lys

p.N39K

P49755

protein_coding

tolerated(0.06)

benign(0.104)

TCGA-CK-4951-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

TMED10

SNV

Missense_Mutation

c.457N>T

p.Arg153Cys

p.R153C

P49755

protein_coding

tolerated(0.06)

benign(0.427)

TCGA-D5-6928-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

TMED10

SNV

Missense_Mutation

c.490G>T

p.Asp164Tyr

p.D164Y

P49755

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

TMED10

SNV

Missense_Mutation

novel

c.373G>T

p.Asp125Tyr

p.D125Y

P49755

protein_coding

tolerated(0.15)

benign(0.209)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

TMED10

SNV

Missense_Mutation

c.29G>T

p.Arg10Leu

p.R10L

P49755

protein_coding

tolerated_low_confidence(0.1)

benign(0)

TCGA-B5-A0K6-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

TMED10

SNV

Missense_Mutation

c.5N>T

p.Ser2Phe

p.S2F

P49755

protein_coding

tolerated_low_confidence(0.15)

benign(0)

TCGA-D1-A167-01

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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