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: MED24

Gene summary for MED24

Gene summary.

Gene information	Species	Human
	Gene symbol	MED24
	Gene ID	9862
	Gene name	mediator complex subunit 24
	Gene Alias	ARC100
	Cytomap	17q21.1
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	O75448

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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
9862	MED24	GSM4909291	Human	Breast	IDC	3.06e-28	7.46e-01	0.1753
9862	MED24	GSM4909292	Human	Breast	IDC	1.26e-06	6.82e-01	0.1236
9862	MED24	GSM4909319	Human	Breast	IDC	1.48e-02	-7.76e-02	0.1563
9862	MED24	NCCBC14	Human	Breast	DCIS	7.04e-06	3.97e-01	0.2021
9862	MED24	NCCBC5	Human	Breast	DCIS	3.33e-03	2.86e-01	0.2046
9862	MED24	DCIS2	Human	Breast	DCIS	2.57e-19	3.52e-02	0.0085
9862	MED24	HTA11_2487_2000001011	Human	Colorectum	SER	1.77e-03	2.93e-01	-0.1808
9862	MED24	HTA11_1938_2000001011	Human	Colorectum	AD	2.49e-09	5.29e-01	-0.0811
9862	MED24	HTA11_347_2000001011	Human	Colorectum	AD	2.55e-12	4.40e-01	-0.1954
9862	MED24	HTA11_3361_2000001011	Human	Colorectum	AD	8.23e-08	5.25e-01	-0.1207
9862	MED24	HTA11_83_2000001011	Human	Colorectum	SER	3.15e-05	3.70e-01	-0.1526
9862	MED24	HTA11_696_2000001011	Human	Colorectum	AD	2.45e-13	5.80e-01	-0.1464
9862	MED24	HTA11_866_2000001011	Human	Colorectum	AD	7.56e-10	4.24e-01	-0.1001
9862	MED24	HTA11_1391_2000001011	Human	Colorectum	AD	2.09e-19	7.49e-01	-0.059
9862	MED24	HTA11_546_2000001011	Human	Colorectum	AD	1.48e-06	5.53e-01	-0.0842
9862	MED24	HTA11_866_3004761011	Human	Colorectum	AD	1.38e-13	4.99e-01	0.096
9862	MED24	HTA11_7663_2000001011	Human	Colorectum	SER	3.64e-02	4.64e-01	0.0131
9862	MED24	HTA11_10623_2000001011	Human	Colorectum	AD	8.24e-06	5.57e-01	-0.0177
9862	MED24	HTA11_10711_2000001011	Human	Colorectum	AD	2.01e-07	4.05e-01	0.0338
9862	MED24	HTA11_7696_3000711011	Human	Colorectum	AD	2.22e-10	4.95e-01	0.0674

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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
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
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

∗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:0016570	Colorectum	MSS	histone modification	113/3467	463/18723	8.37e-04	8.68e-03	113
GO:00165701	Colorectum	FAP	histone modification	94/2622	463/18723	1.06e-04	1.76e-03	94
GO:001657015	Esophagus	ESCC	histone modification	323/8552	463/18723	2.61e-26	7.88e-24	323
GO:001820514	Esophagus	ESCC	peptidyl-lysine modification	259/8552	376/18723	3.90e-20	5.26e-18	259
GO:001839413	Esophagus	ESCC	peptidyl-lysine acetylation	123/8552	169/18723	6.58e-13	2.94e-11	123
GO:004354313	Esophagus	ESCC	protein acylation	165/8552	243/18723	1.69e-12	7.14e-11	165
GO:000647313	Esophagus	ESCC	protein acetylation	140/8552	201/18723	4.37e-12	1.69e-10	140
GO:001839313	Esophagus	ESCC	internal peptidyl-lysine acetylation	114/8552	158/18723	1.16e-11	4.24e-10	114
GO:000647513	Esophagus	ESCC	internal protein amino acid acetylation	115/8552	160/18723	1.43e-11	5.08e-10	115
GO:00165735	Esophagus	ESCC	histone acetylation	110/8552	152/18723	1.95e-11	6.81e-10	110
GO:00063673	Esophagus	ESCC	transcription initiation from RNA polymerase II promoter	56/8552	77/18723	1.30e-06	1.59e-05	56
GO:000635211	Esophagus	ESCC	DNA-templated transcription, initiation	86/8552	130/18723	1.88e-06	2.19e-05	86
GO:00602603	Esophagus	ESCC	regulation of transcription initiation from RNA polymerase II promoter	25/8552	33/18723	4.30e-04	2.43e-03	25
GO:200014212	Esophagus	ESCC	regulation of DNA-templated transcription, initiation	29/8552	40/18723	5.32e-04	2.93e-03	29
GO:20001443	Esophagus	ESCC	positive regulation of DNA-templated transcription, initiation	21/8552	31/18723	1.10e-02	3.70e-02	21
GO:00064731	Liver	Cirrhotic	protein acetylation	84/4634	201/18723	7.50e-08	2.25e-06	84
GO:00183941	Liver	Cirrhotic	peptidyl-lysine acetylation	73/4634	169/18723	1.08e-07	3.07e-06	73
GO:00435431	Liver	Cirrhotic	protein acylation	95/4634	243/18723	4.73e-07	1.07e-05	95
GO:00182051	Liver	Cirrhotic	peptidyl-lysine modification	134/4634	376/18723	1.29e-06	2.59e-05	134
GO:00064751	Liver	Cirrhotic	internal protein amino acid acetylation	65/4634	160/18723	6.66e-06	1.04e-04	65

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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
hsa0491922	Breast	DCIS	Thyroid hormone signaling pathway	23/846	121/8465	1.78e-03	1.22e-02	9.00e-03	23
hsa0491932	Breast	DCIS	Thyroid hormone signaling pathway	23/846	121/8465	1.78e-03	1.22e-02	9.00e-03	23
hsa04919	Colorectum	AD	Thyroid hormone signaling pathway	51/2092	121/8465	1.71e-05	1.73e-04	1.10e-04	51
hsa049191	Colorectum	AD	Thyroid hormone signaling pathway	51/2092	121/8465	1.71e-05	1.73e-04	1.10e-04	51
hsa049192	Colorectum	SER	Thyroid hormone signaling pathway	40/1580	121/8465	1.02e-04	1.06e-03	7.67e-04	40
hsa049193	Colorectum	SER	Thyroid hormone signaling pathway	40/1580	121/8465	1.02e-04	1.06e-03	7.67e-04	40
hsa049194	Colorectum	MSS	Thyroid hormone signaling pathway	46/1875	121/8465	5.04e-05	4.97e-04	3.05e-04	46
hsa049195	Colorectum	MSS	Thyroid hormone signaling pathway	46/1875	121/8465	5.04e-05	4.97e-04	3.05e-04	46
hsa0491928	Esophagus	ESCC	Thyroid hormone signaling pathway	78/4205	121/8465	6.79e-04	2.23e-03	1.14e-03	78
hsa04919113	Esophagus	ESCC	Thyroid hormone signaling pathway	78/4205	121/8465	6.79e-04	2.23e-03	1.14e-03	78
hsa0491912	Liver	HCC	Thyroid hormone signaling pathway	75/4020	121/8465	8.76e-04	3.38e-03	1.88e-03	75
hsa0491913	Liver	HCC	Thyroid hormone signaling pathway	75/4020	121/8465	8.76e-04	3.38e-03	1.88e-03	75
hsa0491926	Oral cavity	OSCC	Thyroid hormone signaling pathway	73/3704	121/8465	1.63e-04	5.52e-04	2.81e-04	73
hsa04919112	Oral cavity	OSCC	Thyroid hormone signaling pathway	73/3704	121/8465	1.63e-04	5.52e-04	2.81e-04	73

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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

MED24

SNV

Missense_Mutation

novel

c.794N>A

p.Ala265Asp

p.A265D

protein_coding

deleterious(0.01)

possibly_damaging(0.802)

TCGA-A7-A26F-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

MED24

SNV

Missense_Mutation

c.1910N>A

p.Val637Glu

p.V637E

protein_coding

deleterious(0)

probably_damaging(0.923)

TCGA-BH-A0E2-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

MED24

SNV

Missense_Mutation

novel

c.2303T>C

p.Ile768Thr

p.I768T

protein_coding

deleterious(0)

benign(0.127)

TCGA-BH-A8FZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MED24

SNV

Missense_Mutation

c.1988N>A

p.Arg663His

p.R663H

protein_coding

deleterious(0.01)

benign(0.157)

TCGA-D8-A1XL-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide+tamoxifen

MED24

SNV

Missense_Mutation

novel

c.1957N>C

p.Asp653His

p.D653H

protein_coding

deleterious(0)

possibly_damaging(0.834)

TCGA-E2-A1LB-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

MED24

SNV

Missense_Mutation

c.636N>C

p.Glu212Asp

p.E212D

protein_coding

tolerated(0.06)

probably_damaging(0.981)

TCGA-EW-A1J3-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

MED24

insertion

Frame_Shift_Ins

novel

c.939_940insTGGGAGGCCAAGGCGGGTGGATCACGAGGTCAGGAGTTTG

p.Glu314TrpfsTer51

p.E314Wfs*51

protein_coding

TCGA-A2-A0D1-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

MED24

insertion

Nonsense_Mutation

novel

c.861_862insTCTTCAGACCAGAGTTTTACACTCTTAGTCACTGCTCTTTAACTC

p.Thr287_Met288insSerSerAspGlnSerPheThrLeuLeuValThrAlaLeuTerLeu

p.T287_M288insSSDQSFTLLVTAL*L

protein_coding

TCGA-A8-A07J-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

MED24

insertion

Frame_Shift_Ins

novel

c.808_809insC

p.Glu270AlafsTer45

p.E270Afs*45

protein_coding

TCGA-A8-A08Z-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

MED24

insertion

In_Frame_Ins

novel

c.807_808insAGACAGATAGGT

p.Leu269_Glu270insArgGlnIleGly

p.L269_E270insRQIG

protein_coding

TCGA-A8-A08Z-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

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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