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: GCN1

Gene summary for GCN1

Gene summary.

Gene information	Species	Human
	Gene symbol	GCN1
	Gene ID	10985
	Gene name	GCN1 activator of EIF2AK4
	Gene Alias	GCN1L
	Cytomap	12q24.23
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	Q92616

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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
10985	GCN1	P80T-E	Human	Esophagus	ESCC	2.89e-18	5.24e-01	0.155
10985	GCN1	P82T-E	Human	Esophagus	ESCC	6.19e-10	5.15e-01	0.1072
10985	GCN1	P83T-E	Human	Esophagus	ESCC	1.21e-11	2.73e-01	0.1738
10985	GCN1	P89T-E	Human	Esophagus	ESCC	9.83e-06	2.92e-01	0.1752
10985	GCN1	P91T-E	Human	Esophagus	ESCC	6.57e-05	6.07e-01	0.1828
10985	GCN1	P104T-E	Human	Esophagus	ESCC	3.31e-07	2.92e-01	0.0931
10985	GCN1	P107T-E	Human	Esophagus	ESCC	3.53e-18	5.12e-01	0.171
10985	GCN1	P127T-E	Human	Esophagus	ESCC	1.09e-08	1.21e-01	0.0826
10985	GCN1	P128T-E	Human	Esophagus	ESCC	2.38e-07	4.10e-01	0.1241
10985	GCN1	P130T-E	Human	Esophagus	ESCC	3.97e-42	7.25e-01	0.1676
10985	GCN1	HCC1_Meng	Human	Liver	HCC	8.14e-47	9.53e-02	0.0246
10985	GCN1	HCC2_Meng	Human	Liver	HCC	1.07e-07	3.13e-02	0.0107
10985	GCN1	HCC1	Human	Liver	HCC	7.08e-07	3.69e+00	0.5336
10985	GCN1	HCC2	Human	Liver	HCC	3.76e-23	4.13e+00	0.5341
10985	GCN1	S014	Human	Liver	HCC	3.51e-13	5.49e-01	0.2254
10985	GCN1	S015	Human	Liver	HCC	4.15e-12	6.44e-01	0.2375
10985	GCN1	S016	Human	Liver	HCC	2.97e-21	7.17e-01	0.2243
10985	GCN1	S027	Human	Liver	HCC	1.10e-09	7.98e-01	0.2446
10985	GCN1	S028	Human	Liver	HCC	4.36e-17	7.76e-01	0.2503
10985	GCN1	S029	Human	Liver	HCC	3.23e-16	8.24e-01	0.2581

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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:0006417	Colorectum	AD	regulation of translation	141/3918	468/18723	1.32e-06	4.22e-05	141
GO:0031667	Colorectum	AD	response to nutrient levels	138/3918	474/18723	1.22e-05	2.68e-04	138
GO:0033674	Colorectum	AD	positive regulation of kinase activity	131/3918	467/18723	1.28e-04	1.85e-03	131
GO:0042594	Colorectum	AD	response to starvation	63/3918	197/18723	1.77e-04	2.38e-03	63
GO:0043620	Colorectum	AD	regulation of DNA-templated transcription in response to stress	23/3918	53/18723	1.86e-04	2.49e-03	23
GO:0071496	Colorectum	AD	cellular response to external stimulus	94/3918	320/18723	1.98e-04	2.64e-03	94
GO:0036003	Colorectum	AD	positive regulation of transcription from RNA polymerase II promoter in response to stress	13/3918	24/18723	3.45e-04	4.03e-03	13
GO:0009267	Colorectum	AD	cellular response to starvation	51/3918	156/18723	3.90e-04	4.44e-03	51
GO:0043618	Colorectum	AD	regulation of transcription from RNA polymerase II promoter in response to stress	20/3918	47/18723	6.54e-04	6.75e-03	20
GO:0031668	Colorectum	AD	cellular response to extracellular stimulus	71/3918	246/18723	1.86e-03	1.52e-02	71
GO:0031669	Colorectum	AD	cellular response to nutrient levels	63/3918	215/18723	2.19e-03	1.73e-02	63
GO:00064172	Colorectum	MSS	regulation of translation	134/3467	468/18723	4.43e-08	2.38e-06	134
GO:00316672	Colorectum	MSS	response to nutrient levels	125/3467	474/18723	1.24e-05	2.88e-04	125
GO:00336742	Colorectum	MSS	positive regulation of kinase activity	122/3467	467/18723	2.50e-05	5.21e-04	122
GO:00425942	Colorectum	MSS	response to starvation	56/3467	197/18723	4.25e-04	5.21e-03	56
GO:00360032	Colorectum	MSS	positive regulation of transcription from RNA polymerase II promoter in response to stress	12/3467	24/18723	4.68e-04	5.50e-03	12
GO:00436202	Colorectum	MSS	regulation of DNA-templated transcription in response to stress	20/3467	53/18723	7.91e-04	8.36e-03	20
GO:00714962	Colorectum	MSS	cellular response to external stimulus	82/3467	320/18723	9.30e-04	9.44e-03	82
GO:00436181	Colorectum	MSS	regulation of transcription from RNA polymerase II promoter in response to stress	18/3467	47/18723	1.17e-03	1.13e-02	18
GO:00092672	Colorectum	MSS	cellular response to starvation	44/3467	156/18723	1.96e-03	1.69e-02	44

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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

GCN1

SNV

Missense_Mutation

c.4039G>T

p.Ala1347Ser

p.A1347S

Q92616

protein_coding

deleterious(0.04)

probably_damaging(0.929)

TCGA-A8-A07L-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

GCN1

SNV

Missense_Mutation

c.2092N>T

p.Pro698Ser

p.P698S

Q92616

protein_coding

tolerated(0.17)

benign(0.079)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GCN1

SNV

Missense_Mutation

c.3985N>G

p.His1329Asp

p.H1329D

Q92616

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AO-A03T-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

GCN1

SNV

Missense_Mutation

novel

c.2132N>T

p.Pro711Leu

p.P711L

Q92616

protein_coding

tolerated(0.21)

benign(0.098)

TCGA-AO-A0JB-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

GCN1

SNV

Missense_Mutation

rs770357732

c.7949N>A

p.Arg2650Lys

p.R2650K

Q92616

protein_coding

tolerated(1)

benign(0.062)

TCGA-AO-A124-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

GCN1

SNV

Missense_Mutation

c.1711G>A

p.Ala571Thr

p.A571T

Q92616

protein_coding

tolerated(0.39)

benign(0.013)

TCGA-AR-A251-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

GCN1

SNV

Missense_Mutation

c.1175N>T

p.Pro392Leu

p.P392L

Q92616

protein_coding

deleterious(0.05)

benign(0.015)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

GCN1

SNV

Missense_Mutation

novel

c.221N>C

p.Ile74Thr

p.I74T

Q92616

protein_coding

deleterious(0)

possibly_damaging(0.599)

TCGA-BH-A18G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

GCN1

SNV

Missense_Mutation

c.3531N>T

p.Gln1177His

p.Q1177H

Q92616

protein_coding

tolerated(0.05)

benign(0.082)

TCGA-D8-A1Y1-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

tamoxiphen

GCN1

SNV

Missense_Mutation

c.3528N>T

p.Arg1176Ser

p.R1176S

Q92616

protein_coding

deleterious(0.03)

probably_damaging(0.994)

TCGA-E2-A1L6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

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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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