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: INSIG1

Gene summary for INSIG1

Gene summary.

Gene information	Species	Human
	Gene symbol	INSIG1
	Gene ID	3638
	Gene name	insulin induced gene 1
	Gene Alias	CL6
	Cytomap	7q36.3
	Gene Type	protein-coding
	GO ID	GO:0001501
	UniProtAcc	A4D2M9

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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
3638	INSIG1	LZE2T	Human	Esophagus	ESCC	2.88e-04	7.22e-01	0.082
3638	INSIG1	LZE4T	Human	Esophagus	ESCC	2.76e-03	5.46e-01	0.0811
3638	INSIG1	LZE8T	Human	Esophagus	ESCC	7.53e-03	-1.77e-01	0.067
3638	INSIG1	LZE20T	Human	Esophagus	ESCC	6.94e-07	3.14e-02	0.0662
3638	INSIG1	LZE24T	Human	Esophagus	ESCC	2.17e-05	6.54e-01	0.0596
3638	INSIG1	LZE21T	Human	Esophagus	ESCC	1.74e-03	8.17e-01	0.0655
3638	INSIG1	LZE6T	Human	Esophagus	ESCC	7.89e-04	-2.89e-01	0.0845
3638	INSIG1	P2T-E	Human	Esophagus	ESCC	8.61e-04	2.69e-01	0.1177
3638	INSIG1	P4T-E	Human	Esophagus	ESCC	1.44e-34	1.94e+00	0.1323
3638	INSIG1	P5T-E	Human	Esophagus	ESCC	5.11e-34	1.71e+00	0.1327
3638	INSIG1	P8T-E	Human	Esophagus	ESCC	8.58e-06	3.81e-01	0.0889
3638	INSIG1	P9T-E	Human	Esophagus	ESCC	8.46e-10	7.51e-01	0.1131
3638	INSIG1	P10T-E	Human	Esophagus	ESCC	1.25e-40	1.86e+00	0.116
3638	INSIG1	P11T-E	Human	Esophagus	ESCC	1.23e-04	9.38e-01	0.1426
3638	INSIG1	P12T-E	Human	Esophagus	ESCC	3.20e-07	3.15e-01	0.1122
3638	INSIG1	P15T-E	Human	Esophagus	ESCC	3.38e-27	1.46e+00	0.1149
3638	INSIG1	P17T-E	Human	Esophagus	ESCC	1.27e-02	-1.90e-02	0.1278
3638	INSIG1	P20T-E	Human	Esophagus	ESCC	9.48e-16	8.70e-01	0.1124
3638	INSIG1	P21T-E	Human	Esophagus	ESCC	6.17e-19	1.43e+00	0.1617
3638	INSIG1	P22T-E	Human	Esophagus	ESCC	4.16e-23	9.29e-01	0.1236

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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
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
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:19026523	Oral cavity	OSCC	secondary alcohol metabolic process	79/7305	147/18723	1.98e-04	1.33e-03	79
GO:19038288	Oral cavity	OSCC	negative regulation of cellular protein localization	65/7305	117/18723	2.05e-04	1.36e-03	65
GO:00708614	Oral cavity	OSCC	regulation of protein exit from endoplasmic reticulum	20/7305	27/18723	2.32e-04	1.51e-03	20
GO:00066317	Oral cavity	OSCC	fatty acid metabolic process	186/7305	390/18723	2.65e-04	1.69e-03	186
GO:00161262	Oral cavity	OSCC	sterol biosynthetic process	39/7305	64/18723	3.12e-04	1.94e-03	39
GO:00066945	Oral cavity	OSCC	steroid biosynthetic process	89/7305	173/18723	5.77e-04	3.30e-03	89
GO:00903173	Oral cavity	OSCC	negative regulation of intracellular protein transport	27/7305	42/18723	8.00e-04	4.29e-03	27
GO:00323874	Oral cavity	OSCC	negative regulation of intracellular transport	35/7305	58/18723	8.06e-04	4.32e-03	35
GO:00082033	Oral cavity	OSCC	cholesterol metabolic process	72/7305	137/18723	8.63e-04	4.55e-03	72
GO:00708623	Oral cavity	OSCC	negative regulation of protein exit from endoplasmic reticulum	9/7305	10/18723	1.36e-03	6.62e-03	9
GO:19016173	Oral cavity	OSCC	organic hydroxy compound biosynthetic process	115/7305	237/18723	1.73e-03	8.18e-03	115
GO:00161253	Oral cavity	OSCC	sterol metabolic process	77/7305	152/18723	2.26e-03	1.00e-02	77
GO:00468906	Oral cavity	OSCC	regulation of lipid biosynthetic process	85/7305	171/18723	2.79e-03	1.21e-02	85
GO:00192167	Oral cavity	OSCC	regulation of lipid metabolic process	154/7305	331/18723	3.00e-03	1.30e-02	154
GO:00620128	Oral cavity	OSCC	regulation of small molecule metabolic process	155/7305	334/18723	3.30e-03	1.41e-02	155
GO:00603484	Oral cavity	OSCC	bone development	99/7305	205/18723	4.13e-03	1.68e-02	99
GO:00329334	Oral cavity	OSCC	SREBP signaling pathway	11/7305	15/18723	7.49e-03	2.75e-02	11
GO:00901103	Oral cavity	OSCC	COPII-coated vesicle cargo loading	11/7305	15/18723	7.49e-03	2.75e-02	11
GO:00082024	Oral cavity	OSCC	steroid metabolic process	146/7305	319/18723	7.78e-03	2.85e-02	146
GO:00508103	Oral cavity	OSCC	regulation of steroid biosynthetic process	37/7305	69/18723	9.61e-03	3.41e-02	37

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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

INSIG1

SNV

Missense_Mutation

novel

c.698N>A

p.Val233Asp

p.V233D

O15503

protein_coding

deleterious(0)

probably_damaging(0.969)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

INSIG1

deletion

In_Frame_Del

c.776_778delTGG

p.Val259del

p.V259del

O15503

protein_coding

TCGA-A8-A07W-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

exemestane

INSIG1

SNV

Missense_Mutation

c.108G>C

p.Glu36Asp

p.E36D

O15503

protein_coding

tolerated_low_confidence(0.18)

benign(0)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

INSIG1

SNV

Missense_Mutation

novel

c.349N>A

p.Glu117Lys

p.E117K

O15503

protein_coding

tolerated(0.1)

probably_damaging(0.996)

TCGA-VS-A9V0-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

INSIG1

SNV

Missense_Mutation

rs780785188

c.769N>A

p.Val257Ile

p.V257I

O15503

protein_coding

tolerated(0.38)

probably_damaging(0.995)

TCGA-AZ-4313-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

INSIG1

deletion

In_Frame_Del

novel

c.276_278delNNN

p.Phe92_Ser93delinsLeu

p.F92_S93delinsL

O15503

protein_coding

TCGA-AA-3845-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

INSIG1

SNV

Missense_Mutation

novel

c.737N>A

p.Ser246Tyr

p.S246Y

O15503

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AJ-A5DW-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

INSIG1

SNV

Missense_Mutation

novel

c.757T>G

p.Phe253Val

p.F253V

O15503

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

INSIG1

SNV

Missense_Mutation

novel

c.409N>A

p.Ala137Thr

p.A137T

O15503

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-EO-A22R-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

INSIG1

SNV

Missense_Mutation

novel

c.293N>G

p.Leu98Arg

p.L98R

O15503

protein_coding

deleterious(0)

probably_damaging(0.955)

TCGA-EY-A1GI-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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