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: MED1

Gene summary for MED1

Gene summary.

Gene information	Species	Human
	Gene symbol	MED1
	Gene ID	5469
	Gene name	mediator complex subunit 1
	Gene Alias	CRSP1
	Cytomap	17q12
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q15648

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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
5469	MED1	GSM4909291	Human	Breast	IDC	2.79e-50	1.04e+00	0.1753
5469	MED1	GSM4909292	Human	Breast	IDC	2.16e-03	4.18e-01	0.1236
5469	MED1	GSM4909293	Human	Breast	IDC	1.82e-56	8.34e-01	0.1581
5469	MED1	GSM4909317	Human	Breast	IDC	2.82e-02	1.51e-01	0.1355
5469	MED1	DCIS2	Human	Breast	DCIS	2.67e-20	8.42e-02	0.0085
5469	MED1	LZE2T	Human	Esophagus	ESCC	1.06e-02	2.93e-01	0.082
5469	MED1	LZE4T	Human	Esophagus	ESCC	3.44e-08	2.66e-01	0.0811
5469	MED1	LZE5T	Human	Esophagus	ESCC	3.23e-07	3.71e-01	0.0514
5469	MED1	LZE7T	Human	Esophagus	ESCC	1.35e-09	4.22e-01	0.0667
5469	MED1	LZE8T	Human	Esophagus	ESCC	1.06e-02	1.75e-01	0.067
5469	MED1	LZE22T	Human	Esophagus	ESCC	3.41e-03	1.82e-01	0.068
5469	MED1	LZE24T	Human	Esophagus	ESCC	3.13e-17	4.21e-01	0.0596
5469	MED1	LZE21T	Human	Esophagus	ESCC	8.40e-03	1.84e-01	0.0655
5469	MED1	P1T-E	Human	Esophagus	ESCC	2.31e-06	2.79e-01	0.0875
5469	MED1	P2T-E	Human	Esophagus	ESCC	1.92e-17	3.23e-01	0.1177
5469	MED1	P4T-E	Human	Esophagus	ESCC	2.12e-16	3.12e-01	0.1323
5469	MED1	P5T-E	Human	Esophagus	ESCC	9.36e-08	1.65e-01	0.1327
5469	MED1	P8T-E	Human	Esophagus	ESCC	9.37e-19	3.74e-01	0.0889
5469	MED1	P9T-E	Human	Esophagus	ESCC	1.82e-10	2.21e-01	0.1131
5469	MED1	P10T-E	Human	Esophagus	ESCC	7.15e-07	1.64e-01	0.116

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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
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

∗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:005254841	Stomach	WIM	regulation of endopeptidase activity	26/426	432/18723	7.15e-06	3.54e-04	26
GO:005254741	Stomach	WIM	regulation of peptidase activity	27/426	461/18723	7.84e-06	3.79e-04	27
GO:00018194	Stomach	WIM	positive regulation of cytokine production	25/426	467/18723	7.41e-05	2.13e-03	25
GO:190495141	Stomach	WIM	positive regulation of establishment of protein localization	19/426	319/18723	1.40e-04	3.55e-03	19
GO:005122241	Stomach	WIM	positive regulation of protein transport	18/426	303/18723	2.15e-04	4.83e-03	18
GO:000690011	Stomach	WIM	vesicle budding from membrane	7/426	61/18723	4.55e-04	8.34e-03	7
GO:00513464	Stomach	WIM	negative regulation of hydrolase activity	20/426	379/18723	4.60e-04	8.37e-03	20
GO:004586141	Stomach	WIM	negative regulation of proteolysis	19/426	351/18723	4.65e-04	8.38e-03	19
GO:00109514	Stomach	WIM	negative regulation of endopeptidase activity	15/426	252/18723	6.93e-04	1.12e-02	15
GO:00104664	Stomach	WIM	negative regulation of peptidase activity	15/426	262/18723	1.03e-03	1.54e-02	15
GO:00507144	Stomach	WIM	positive regulation of protein secretion	10/426	137/18723	1.18e-03	1.68e-02	10
GO:00326124	Stomach	WIM	interleukin-1 production	9/426	128/18723	2.64e-03	3.02e-02	9
GO:00326524	Stomach	WIM	regulation of interleukin-1 production	9/426	128/18723	2.64e-03	3.02e-02	9
GO:0043279	Stomach	WIM	response to alkaloid	8/426	115/18723	4.79e-03	4.33e-02	8
GO:005104711	Stomach	WIM	positive regulation of secretion	15/426	310/18723	5.13e-03	4.52e-02	15
GO:00525475	Stomach	SIM	regulation of peptidase activity	54/708	461/18723	1.46e-13	6.25e-11	54
GO:00525485	Stomach	SIM	regulation of endopeptidase activity	51/708	432/18723	5.26e-13	2.07e-10	51
GO:00513465	Stomach	SIM	negative regulation of hydrolase activity	42/708	379/18723	4.58e-10	8.00e-08	42
GO:00104665	Stomach	SIM	negative regulation of peptidase activity	33/708	262/18723	1.39e-09	2.26e-07	33
GO:00458615	Stomach	SIM	negative regulation of proteolysis	39/708	351/18723	1.80e-09	2.79e-07	39

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0491916	Breast	IDC	Thyroid hormone signaling pathway	23/867	121/8465	2.45e-03	1.69e-02	1.27e-02	23
hsa0491917	Breast	IDC	Thyroid hormone signaling pathway	23/867	121/8465	2.45e-03	1.69e-02	1.27e-02	23
hsa0491928	Esophagus	ESCC	Thyroid hormone signaling pathway	78/4205	121/8465	6.79e-04	2.23e-03	1.14e-03	78
hsa015227	Esophagus	ESCC	Endocrine resistance	63/4205	98/8465	2.38e-03	6.58e-03	3.37e-03	63
hsa04919113	Esophagus	ESCC	Thyroid hormone signaling pathway	78/4205	121/8465	6.79e-04	2.23e-03	1.14e-03	78
hsa0152215	Esophagus	ESCC	Endocrine resistance	63/4205	98/8465	2.38e-03	6.58e-03	3.37e-03	63
hsa0491912	Liver	HCC	Thyroid hormone signaling pathway	75/4020	121/8465	8.76e-04	3.38e-03	1.88e-03	75
hsa01522	Liver	HCC	Endocrine resistance	58/4020	98/8465	1.28e-02	3.19e-02	1.78e-02	58
hsa0491913	Liver	HCC	Thyroid hormone signaling pathway	75/4020	121/8465	8.76e-04	3.38e-03	1.88e-03	75
hsa015221	Liver	HCC	Endocrine resistance	58/4020	98/8465	1.28e-02	3.19e-02	1.78e-02	58
hsa015226	Oral cavity	OSCC	Endocrine resistance	63/3704	98/8465	3.09e-05	1.31e-04	6.67e-05	63
hsa0491926	Oral cavity	OSCC	Thyroid hormone signaling pathway	73/3704	121/8465	1.63e-04	5.52e-04	2.81e-04	73
hsa0152214	Oral cavity	OSCC	Endocrine resistance	63/3704	98/8465	3.09e-05	1.31e-04	6.67e-05	63
hsa04919112	Oral cavity	OSCC	Thyroid hormone signaling pathway	73/3704	121/8465	1.63e-04	5.52e-04	2.81e-04	73
hsa0152221	Prostate	Tumor	Endocrine resistance	37/1791	98/8465	1.17e-04	7.42e-04	4.60e-04	37
hsa0491925	Prostate	Tumor	Thyroid hormone signaling pathway	40/1791	121/8465	1.47e-03	6.26e-03	3.88e-03	40
hsa0152231	Prostate	Tumor	Endocrine resistance	37/1791	98/8465	1.17e-04	7.42e-04	4.60e-04	37
hsa0491934	Prostate	Tumor	Thyroid hormone signaling pathway	40/1791	121/8465	1.47e-03	6.26e-03	3.88e-03	40

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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

MED1

SNV

Missense_Mutation

novel

c.4150N>T

p.Val1384Leu

p.V1384L

Q15648

protein_coding

deleterious_low_confidence(0.04)

benign(0.01)

TCGA-AC-A3TM-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cytoxan

MED1

SNV

Missense_Mutation

c.3950N>A

p.Ser1317Asn

p.S1317N

Q15648

protein_coding

deleterious_low_confidence(0.03)

benign(0.037)

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MED1

SNV

Missense_Mutation

c.3527N>T

p.Gly1176Val

p.G1176V

Q15648

protein_coding

tolerated_low_confidence(0.19)

possibly_damaging(0.609)

TCGA-AO-A0JM-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

MED1

SNV

Missense_Mutation

novel

c.3094N>C

p.Thr1032Pro

p.T1032P

Q15648

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.996)

TCGA-B6-A1KF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MED1

SNV

Missense_Mutation

rs764603504

c.2012N>A

p.Ser671Tyr

p.S671Y

Q15648

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.979)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

MED1

SNV

Missense_Mutation

c.2672N>G

p.Asp891Gly

p.D891G

Q15648

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.94)

TCGA-D8-A1Y1-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

MED1

SNV

Missense_Mutation

c.440T>C

p.Phe147Ser

p.F147S

Q15648

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-EW-A1OV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

epirubicin

MED1

insertion

In_Frame_Ins

novel

c.4587_4588insAAAAAATCTCATAGCATCAAG

p.Lys1523_Lys1529dup

p.K1523_K1529dup

Q15648

protein_coding

TCGA-A7-A0DB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

MED1

deletion

Frame_Shift_Del

c.1709delN

p.Gly570ValfsTer9

p.G570Vfs*9

Q15648

protein_coding

TCGA-AN-A0AK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MED1

SNV

Missense_Mutation

rs199907019

c.1883N>T

p.Thr628Met

p.T628M

Q15648

protein_coding

deleterious_low_confidence(0)

benign(0.062)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

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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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