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	C06	Human	Oral cavity	OSCC	9.18e-06	1.23e+00	0.2699
3638	INSIG1	C08	Human	Oral cavity	OSCC	9.58e-58	1.50e+00	0.1919
3638	INSIG1	C09	Human	Oral cavity	OSCC	2.86e-07	3.39e-01	0.1431
3638	INSIG1	LN22	Human	Oral cavity	OSCC	1.07e-04	8.37e-01	0.1733
3638	INSIG1	LN46	Human	Oral cavity	OSCC	8.92e-11	4.66e-01	0.1666
3638	INSIG1	EOLP-1	Human	Oral cavity	EOLP	3.35e-05	3.70e-01	-0.0202
3638	INSIG1	SYSMH1	Human	Oral cavity	OSCC	1.85e-02	3.83e-01	0.1127
3638	INSIG1	SYSMH6	Human	Oral cavity	OSCC	1.12e-02	3.35e-01	0.1275
3638	INSIG1	P1_S1_AK	Human	Skin	AK	1.00e-10	-5.60e-01	-0.3399
3638	INSIG1	P2_S3_AK	Human	Skin	AK	1.76e-09	-5.50e-01	-0.3287
3638	INSIG1	P2_S4_SCCIS	Human	Skin	SCCIS	2.83e-11	-5.25e-01	-0.3043
3638	INSIG1	P3_S6_AK	Human	Skin	AK	1.00e-09	-5.60e-01	-0.3256
3638	INSIG1	P4_S8_cSCC	Human	Skin	cSCC	2.40e-06	-5.63e-01	-0.3095
3638	INSIG1	P5_S10_cSCC	Human	Skin	cSCC	3.26e-05	-4.40e-01	-0.299
3638	INSIG1	P4_cSCC	Human	Skin	cSCC	1.41e-06	-4.25e-01	-0.00290000000000005
3638	INSIG1	cSCC_p1	Human	Skin	cSCC	4.43e-09	-5.37e-01	-0.1916
3638	INSIG1	cSCC_p10	Human	Skin	cSCC	6.46e-08	-5.20e-01	-0.2095
3638	INSIG1	cSCC_p11	Human	Skin	cSCC	3.90e-13	-5.91e-01	-0.2102
3638	INSIG1	cSCC_p3	Human	Skin	cSCC	2.40e-05	-4.96e-01	-0.2085
3638	INSIG1	cSCC_p4	Human	Skin	cSCC	3.63e-15	-5.85e-01	-0.2022

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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:004819318	Esophagus	ESCC	Golgi vesicle transport	231/8552	296/18723	1.82e-30	9.63e-28	231
GO:003238618	Esophagus	ESCC	regulation of intracellular transport	243/8552	337/18723	3.20e-23	7.25e-21	243
GO:001605014	Esophagus	ESCC	vesicle organization	211/8552	300/18723	2.85e-18	2.87e-16	211
GO:0033157110	Esophagus	ESCC	regulation of intracellular protein transport	169/8552	229/18723	3.31e-18	3.23e-16	169
GO:000688815	Esophagus	ESCC	endoplasmic reticulum to Golgi vesicle-mediated transport	102/8552	130/18723	1.73e-14	9.22e-13	102
GO:0006900111	Esophagus	ESCC	vesicle budding from membrane	54/8552	61/18723	2.66e-12	1.07e-10	54
GO:0045185111	Esophagus	ESCC	maintenance of protein location	71/8552	94/18723	3.41e-09	7.24e-08	71
GO:0051235110	Esophagus	ESCC	maintenance of location	200/8552	327/18723	1.01e-08	2.02e-07	200
GO:0032507110	Esophagus	ESCC	maintenance of protein location in cell	52/8552	65/18723	1.41e-08	2.77e-07	52
GO:009011414	Esophagus	ESCC	COPII-coated vesicle budding	27/8552	29/18723	8.09e-08	1.39e-06	27
GO:007259517	Esophagus	ESCC	maintenance of protein localization in organelle	36/8552	42/18723	8.46e-08	1.44e-06	36
GO:000698416	Esophagus	ESCC	ER-nucleus signaling pathway	38/8552	46/18723	2.70e-07	4.00e-06	38
GO:190165319	Esophagus	ESCC	cellular response to peptide	208/8552	359/18723	1.68e-06	2.01e-05	208
GO:0043434111	Esophagus	ESCC	response to peptide hormone	234/8552	414/18723	4.93e-06	5.21e-05	234
GO:003286918	Esophagus	ESCC	cellular response to insulin stimulus	124/8552	203/18723	6.63e-06	6.75e-05	124
GO:003286818	Esophagus	ESCC	response to insulin	156/8552	264/18723	7.21e-06	7.20e-05	156
GO:00060668	Esophagus	ESCC	alcohol metabolic process	202/8552	353/18723	7.32e-06	7.26e-05	202
GO:003252714	Esophagus	ESCC	protein exit from endoplasmic reticulum	37/8552	48/18723	8.99e-06	8.65e-05	37
GO:007097218	Esophagus	ESCC	protein localization to endoplasmic reticulum	52/8552	74/18723	1.58e-05	1.42e-04	52
GO:00161263	Esophagus	ESCC	sterol biosynthetic process	46/8552	64/18723	1.91e-05	1.67e-04	46

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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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