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: IAH1

Gene summary for IAH1

Gene summary.

Gene information	Species	Human
	Gene symbol	IAH1
	Gene ID	285148
	Gene name	isoamyl acetate hydrolyzing esterase 1 (putative)
	Gene Alias	IAH1
	Cytomap	2p25.1
	Gene Type	protein-coding
	GO ID	GO:0006629
	UniProtAcc	A0A140VJL6

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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
285148	IAH1	LZE2D	Human	Esophagus	HGIN	3.88e-02	2.73e-01	0.0642
285148	IAH1	LZE2T	Human	Esophagus	ESCC	4.58e-04	7.12e-01	0.082
285148	IAH1	LZE4T	Human	Esophagus	ESCC	1.17e-20	5.76e-01	0.0811
285148	IAH1	LZE7T	Human	Esophagus	ESCC	6.82e-13	7.63e-01	0.0667
285148	IAH1	LZE8T	Human	Esophagus	ESCC	5.52e-06	3.38e-01	0.067
285148	IAH1	LZE20T	Human	Esophagus	ESCC	4.15e-02	1.35e-01	0.0662
285148	IAH1	LZE24T	Human	Esophagus	ESCC	6.17e-20	6.08e-01	0.0596
285148	IAH1	LZE6T	Human	Esophagus	ESCC	1.16e-18	9.13e-01	0.0845
285148	IAH1	P1T-E	Human	Esophagus	ESCC	1.67e-07	4.80e-01	0.0875
285148	IAH1	P2T-E	Human	Esophagus	ESCC	6.44e-43	8.78e-01	0.1177
285148	IAH1	P4T-E	Human	Esophagus	ESCC	8.57e-55	1.14e+00	0.1323
285148	IAH1	P5T-E	Human	Esophagus	ESCC	6.20e-45	1.04e+00	0.1327
285148	IAH1	P8T-E	Human	Esophagus	ESCC	3.71e-23	5.04e-01	0.0889
285148	IAH1	P9T-E	Human	Esophagus	ESCC	5.37e-30	7.82e-01	0.1131
285148	IAH1	P10T-E	Human	Esophagus	ESCC	5.56e-76	1.39e+00	0.116
285148	IAH1	P11T-E	Human	Esophagus	ESCC	8.04e-28	1.28e+00	0.1426
285148	IAH1	P12T-E	Human	Esophagus	ESCC	2.25e-73	1.30e+00	0.1122
285148	IAH1	P15T-E	Human	Esophagus	ESCC	8.32e-20	6.24e-01	0.1149
285148	IAH1	P16T-E	Human	Esophagus	ESCC	2.44e-40	6.52e-01	0.1153
285148	IAH1	P17T-E	Human	Esophagus	ESCC	3.97e-11	5.52e-01	0.1278

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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: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

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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

IAH1

SNV

Missense_Mutation

c.737N>C

p.Gly246Ala

p.G246A

Q2TAA2

protein_coding

tolerated_low_confidence(0.08)

possibly_damaging(0.714)

TCGA-A8-A09I-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

IAH1

SNV

Missense_Mutation

c.199N>T

p.Pro67Ser

p.P67S

Q2TAA2

protein_coding

deleterious(0.01)

probably_damaging(0.914)

TCGA-EK-A2PM-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

IAH1

SNV

Missense_Mutation

c.255N>A

p.Phe85Leu

p.F85L

Q2TAA2

protein_coding

deleterious(0.03)

possibly_damaging(0.863)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

IAH1

SNV

Missense_Mutation

novel

c.523N>G

p.Thr175Ala

p.T175A

Q2TAA2

protein_coding

tolerated(0.2)

benign(0.009)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

IAH1

SNV

Missense_Mutation

novel

c.691N>T

p.Arg231Trp

p.R231W

Q2TAA2

protein_coding

deleterious(0.01)

possibly_damaging(0.65)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

IAH1

SNV

Missense_Mutation

novel

c.645N>T

p.Leu215Phe

p.L215F

Q2TAA2

protein_coding

tolerated(0.1)

benign(0.066)

TCGA-AJ-A3QS-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

cisplatin

IAH1

SNV

Missense_Mutation

c.437N>G

p.Ile146Ser

p.I146S

Q2TAA2

protein_coding

tolerated(0.49)

benign(0.109)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

IAH1

SNV

Missense_Mutation

novel

c.634N>A

p.Leu212Ile

p.L212I

Q2TAA2

protein_coding

deleterious(0.03)

probably_damaging(0.936)

TCGA-AP-A056-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

IAH1

SNV

Missense_Mutation

novel

c.382G>T

p.Val128Phe

p.V128F

Q2TAA2

protein_coding

deleterious(0.02)

possibly_damaging(0.701)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

IAH1

SNV

Missense_Mutation

c.455N>G

p.Leu152Arg

p.L152R

Q2TAA2

protein_coding

deleterious(0.02)

benign(0.056)

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

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