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: SIAH1

Gene summary for SIAH1

Gene summary.

Gene information	Species	Human
	Gene symbol	SIAH1
	Gene ID	6477
	Gene name	siah E3 ubiquitin protein ligase 1
	Gene Alias	BURHAS
	Cytomap	16q12.1
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q8IUQ4

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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
6477	SIAH1	LZE4T	Human	Esophagus	ESCC	4.61e-24	6.45e-01	0.0811
6477	SIAH1	LZE7T	Human	Esophagus	ESCC	2.65e-09	3.74e-01	0.0667
6477	SIAH1	LZE8T	Human	Esophagus	ESCC	7.57e-04	4.60e-02	0.067
6477	SIAH1	LZE20T	Human	Esophagus	ESCC	5.98e-11	2.77e-01	0.0662
6477	SIAH1	LZE22D1	Human	Esophagus	HGIN	4.05e-03	6.84e-02	0.0595
6477	SIAH1	LZE22T	Human	Esophagus	ESCC	1.22e-04	4.53e-01	0.068
6477	SIAH1	LZE24T	Human	Esophagus	ESCC	1.15e-21	5.12e-01	0.0596
6477	SIAH1	LZE21T	Human	Esophagus	ESCC	2.70e-05	4.89e-01	0.0655
6477	SIAH1	LZE6T	Human	Esophagus	ESCC	1.01e-03	1.19e-01	0.0845
6477	SIAH1	P1T-E	Human	Esophagus	ESCC	3.23e-21	1.13e+00	0.0875
6477	SIAH1	P2T-E	Human	Esophagus	ESCC	5.58e-18	3.48e-01	0.1177
6477	SIAH1	P4T-E	Human	Esophagus	ESCC	9.00e-25	6.71e-01	0.1323
6477	SIAH1	P5T-E	Human	Esophagus	ESCC	5.98e-33	6.50e-01	0.1327
6477	SIAH1	P8T-E	Human	Esophagus	ESCC	1.44e-21	3.81e-01	0.0889
6477	SIAH1	P9T-E	Human	Esophagus	ESCC	4.17e-14	2.29e-01	0.1131
6477	SIAH1	P10T-E	Human	Esophagus	ESCC	1.43e-27	3.50e-01	0.116
6477	SIAH1	P11T-E	Human	Esophagus	ESCC	1.89e-21	7.61e-01	0.1426
6477	SIAH1	P12T-E	Human	Esophagus	ESCC	3.00e-29	4.98e-01	0.1122
6477	SIAH1	P15T-E	Human	Esophagus	ESCC	4.28e-34	6.50e-01	0.1149
6477	SIAH1	P16T-E	Human	Esophagus	ESCC	8.93e-25	4.27e-01	0.1153

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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

∗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:001049826	Esophagus	HGIN	proteasomal protein catabolic process	139/2587	490/18723	1.20e-17	3.41e-15	139
GO:003164727	Esophagus	HGIN	regulation of protein stability	96/2587	298/18723	2.21e-16	5.76e-14	96
GO:009719327	Esophagus	HGIN	intrinsic apoptotic signaling pathway	90/2587	288/18723	1.50e-14	2.80e-12	90
GO:004316126	Esophagus	HGIN	proteasome-mediated ubiquitin-dependent protein catabolic process	114/2587	412/18723	7.00e-14	1.20e-11	114
GO:200124227	Esophagus	HGIN	regulation of intrinsic apoptotic signaling pathway	58/2587	164/18723	2.57e-12	3.58e-10	58
GO:200123327	Esophagus	HGIN	regulation of apoptotic signaling pathway	97/2587	356/18723	1.36e-11	1.57e-09	97
GO:200124410	Esophagus	HGIN	positive regulation of intrinsic apoptotic signaling pathway	25/2587	58/18723	4.91e-08	2.75e-06	25
GO:200123519	Esophagus	HGIN	positive regulation of apoptotic signaling pathway	41/2587	126/18723	6.06e-08	3.22e-06	41
GO:007099727	Esophagus	HGIN	neuron death	81/2587	361/18723	5.01e-06	1.61e-04	81
GO:199000010	Esophagus	HGIN	amyloid fibril formation	13/2587	34/18723	3.51e-04	5.65e-03	13
GO:005140219	Esophagus	HGIN	neuron apoptotic process	52/2587	246/18723	1.01e-03	1.26e-02	52
GO:0010498111	Esophagus	ESCC	proteasomal protein catabolic process	369/8552	490/18723	1.13e-41	1.80e-38	369
GO:0043161111	Esophagus	ESCC	proteasome-mediated ubiquitin-dependent protein catabolic process	312/8552	412/18723	3.53e-36	4.48e-33	312
GO:0097193111	Esophagus	ESCC	intrinsic apoptotic signaling pathway	222/8552	288/18723	5.87e-28	2.02e-25	222
GO:0031647111	Esophagus	ESCC	regulation of protein stability	223/8552	298/18723	5.76e-25	1.52e-22	223
GO:2001233111	Esophagus	ESCC	regulation of apoptotic signaling pathway	256/8552	356/18723	4.11e-24	1.04e-21	256
GO:2001242111	Esophagus	ESCC	regulation of intrinsic apoptotic signaling pathway	128/8552	164/18723	1.75e-17	1.50e-15	128
GO:2001235110	Esophagus	ESCC	positive regulation of apoptotic signaling pathway	92/8552	126/18723	3.91e-10	1.05e-08	92
GO:0070997111	Esophagus	ESCC	neuron death	216/8552	361/18723	3.49e-08	6.45e-07	216
GO:0051402110	Esophagus	ESCC	neuron apoptotic process	148/8552	246/18723	3.08e-06	3.47e-05	148

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0412026	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa0411510	Esophagus	HGIN	p53 signaling pathway	21/1383	74/8465	6.25e-03	4.25e-02	3.37e-02	21
hsa04120111	Esophagus	HGIN	Ubiquitin mediated proteolysis	49/1383	142/8465	7.78e-08	1.33e-06	1.06e-06	49
hsa0411515	Esophagus	HGIN	p53 signaling pathway	21/1383	74/8465	6.25e-03	4.25e-02	3.37e-02	21
hsa0412027	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0411524	Esophagus	ESCC	p53 signaling pathway	65/4205	74/8465	3.88e-12	6.50e-11	3.33e-11	65
hsa0412036	Esophagus	ESCC	Ubiquitin mediated proteolysis	122/4205	142/8465	6.53e-20	7.29e-18	3.74e-18	122
hsa0411534	Esophagus	ESCC	p53 signaling pathway	65/4205	74/8465	3.88e-12	6.50e-11	3.33e-11	65
hsa0412010	Liver	NAFLD	Ubiquitin mediated proteolysis	44/1043	142/8465	2.59e-09	1.70e-07	1.37e-07	44
hsa0412011	Liver	NAFLD	Ubiquitin mediated proteolysis	44/1043	142/8465	2.59e-09	1.70e-07	1.37e-07	44
hsa0412021	Liver	Cirrhotic	Ubiquitin mediated proteolysis	72/2530	142/8465	1.32e-07	1.97e-06	1.21e-06	72
hsa0412031	Liver	Cirrhotic	Ubiquitin mediated proteolysis	72/2530	142/8465	1.32e-07	1.97e-06	1.21e-06	72
hsa0412041	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa041156	Liver	HCC	p53 signaling pathway	46/4020	74/8465	7.64e-03	2.08e-02	1.16e-02	46
hsa0412051	Liver	HCC	Ubiquitin mediated proteolysis	110/4020	142/8465	1.67e-13	3.74e-12	2.08e-12	110
hsa0411511	Liver	HCC	p53 signaling pathway	46/4020	74/8465	7.64e-03	2.08e-02	1.16e-02	46
hsa0412020	Oral cavity	OSCC	Ubiquitin mediated proteolysis	105/3704	142/8465	1.83e-13	4.37e-12	2.23e-12	105
hsa041159	Oral cavity	OSCC	p53 signaling pathway	57/3704	74/8465	4.99e-09	5.07e-08	2.58e-08	57
hsa04120110	Oral cavity	OSCC	Ubiquitin mediated proteolysis	105/3704	142/8465	1.83e-13	4.37e-12	2.23e-12	105
hsa0411514	Oral cavity	OSCC	p53 signaling pathway	57/3704	74/8465	4.99e-09	5.07e-08	2.58e-08	57

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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

SIAH1

SNV

Missense_Mutation

novel

c.815G>A

p.Arg272Gln

p.R272Q

Q8IUQ4

protein_coding

tolerated(0.08)

probably_damaging(0.97)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

SIAH1

SNV

Missense_Mutation

novel

c.8N>C

p.Gly3Ala

p.G3A

Q8IUQ4

protein_coding

tolerated_low_confidence(1)

possibly_damaging(0.899)

TCGA-VS-A958-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

SIAH1

SNV

Missense_Mutation

c.536N>A

p.Leu179Gln

p.L179Q

Q8IUQ4

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AD-6964-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

folfox

SIAH1

SNV

Missense_Mutation

c.335N>A

p.Ser112Tyr

p.S112Y

Q8IUQ4

protein_coding

deleterious(0.01)

benign(0.049)

TCGA-AD-6964-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

folfox

SIAH1

SNV

Missense_Mutation

c.565N>A

p.Leu189Ile

p.L189I

Q8IUQ4

protein_coding

deleterious(0.04)

possibly_damaging(0.648)

TCGA-A5-A0VP-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

SIAH1

SNV

Missense_Mutation

c.319C>T

p.Arg107Trp

p.R107W

Q8IUQ4

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-A5-A0VQ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

SIAH1

SNV

Missense_Mutation

novel

c.841N>T

p.Ala281Ser

p.A281S

Q8IUQ4

protein_coding

deleterious(0.03)

probably_damaging(0.912)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SIAH1

SNV

Missense_Mutation

novel

c.432N>C

p.Glu144Asp

p.E144D

Q8IUQ4

protein_coding

tolerated(0.27)

benign(0.007)

TCGA-AJ-A5DW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SIAH1

SNV

Missense_Mutation

novel

c.521C>T

p.Ala174Val

p.A174V

Q8IUQ4

protein_coding

tolerated(0.17)

benign(0.127)

TCGA-AP-A1DK-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

SIAH1

SNV

Missense_Mutation

rs200203229

c.86N>T

p.Arg29Ile

p.R29I

Q8IUQ4

protein_coding

tolerated_low_confidence(0.12)

possibly_damaging(0.506)

TCGA-AX-A05Z-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

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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
6477	SIAH1	ENZYME, KINASE		OMIGAPIL	OMIGAPIL

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