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: GNL1

Gene summary for GNL1

Gene summary.

Gene information	Species	Human
	Gene symbol	GNL1
	Gene ID	2794
	Gene name	G protein nucleolar 1 (putative)
	Gene Alias	HSR1
	Cytomap	6p21.33
	Gene Type	protein-coding
	GO ID	GO:0002250
	UniProtAcc	A0A024RCR2

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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
2794	GNL1	LZE4T	Human	Esophagus	ESCC	1.00e-14	3.29e-01	0.0811
2794	GNL1	LZE5T	Human	Esophagus	ESCC	4.85e-04	6.03e-02	0.0514
2794	GNL1	LZE7T	Human	Esophagus	ESCC	8.79e-05	3.02e-01	0.0667
2794	GNL1	LZE8T	Human	Esophagus	ESCC	1.45e-08	1.95e-01	0.067
2794	GNL1	LZE20T	Human	Esophagus	ESCC	1.83e-09	3.37e-02	0.0662
2794	GNL1	LZE22D1	Human	Esophagus	HGIN	7.09e-06	1.29e-01	0.0595
2794	GNL1	LZE22T	Human	Esophagus	ESCC	3.05e-03	5.50e-01	0.068
2794	GNL1	LZE24T	Human	Esophagus	ESCC	6.24e-22	6.59e-01	0.0596
2794	GNL1	LZE21T	Human	Esophagus	ESCC	3.21e-05	3.00e-01	0.0655
2794	GNL1	LZE6T	Human	Esophagus	ESCC	3.53e-07	2.69e-01	0.0845
2794	GNL1	P1T-E	Human	Esophagus	ESCC	3.10e-08	6.85e-01	0.0875
2794	GNL1	P2T-E	Human	Esophagus	ESCC	1.17e-49	9.18e-01	0.1177
2794	GNL1	P4T-E	Human	Esophagus	ESCC	1.88e-26	7.26e-01	0.1323
2794	GNL1	P5T-E	Human	Esophagus	ESCC	1.45e-12	2.09e-01	0.1327
2794	GNL1	P8T-E	Human	Esophagus	ESCC	6.16e-29	4.74e-01	0.0889
2794	GNL1	P9T-E	Human	Esophagus	ESCC	2.40e-12	3.64e-01	0.1131
2794	GNL1	P10T-E	Human	Esophagus	ESCC	7.22e-16	3.84e-01	0.116
2794	GNL1	P11T-E	Human	Esophagus	ESCC	7.84e-17	7.26e-01	0.1426
2794	GNL1	P12T-E	Human	Esophagus	ESCC	9.69e-31	5.84e-01	0.1122
2794	GNL1	P15T-E	Human	Esophagus	ESCC	7.54e-22	5.12e-01	0.1149

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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:015010511	Liver	HCC	protein localization to cell-cell junction	17/7958	21/18723	3.71e-04	2.56e-03	17
GO:190290412	Liver	HCC	negative regulation of supramolecular fiber organization	90/7958	167/18723	1.90e-03	9.69e-03	90
GO:003003822	Liver	HCC	contractile actin filament bundle assembly	60/7958	106/18723	2.34e-03	1.16e-02	60
GO:004314922	Liver	HCC	stress fiber assembly	60/7958	106/18723	2.34e-03	1.16e-02	60
GO:003223122	Liver	HCC	regulation of actin filament bundle assembly	57/7958	105/18723	9.73e-03	3.66e-02	57
GO:00514946	Liver	HCC	negative regulation of cytoskeleton organization	84/7958	163/18723	1.22e-02	4.43e-02	84
GO:011002022	Liver	HCC	regulation of actomyosin structure organization	54/7958	100/18723	1.33e-02	4.76e-02	54
GO:00510565	Lung	IAC	regulation of small GTPase mediated signal transduction	70/2061	302/18723	9.44e-10	1.87e-07	70
GO:00070158	Lung	IAC	actin filament organization	92/2061	442/18723	1.01e-09	1.93e-07	92
GO:00510178	Lung	IAC	actin filament bundle assembly	40/2061	157/18723	2.66e-07	2.14e-05	40
GO:00310327	Lung	IAC	actomyosin structure organization	46/2061	196/18723	4.70e-07	3.10e-05	46
GO:00329708	Lung	IAC	regulation of actin filament-based process	77/2061	397/18723	4.85e-07	3.10e-05	77
GO:00615728	Lung	IAC	actin filament bundle organization	40/2061	161/18723	5.43e-07	3.32e-05	40
GO:00329568	Lung	IAC	regulation of actin cytoskeleton organization	70/2061	358/18723	1.17e-06	6.20e-05	70
GO:00106398	Lung	IAC	negative regulation of organelle organization	68/2061	348/18723	1.69e-06	8.24e-05	68
GO:19029038	Lung	IAC	regulation of supramolecular fiber organization	73/2061	383/18723	1.87e-06	8.87e-05	73
GO:00514947	Lung	IAC	negative regulation of cytoskeleton organization	38/2061	163/18723	5.35e-06	2.08e-04	38
GO:00322318	Lung	IAC	regulation of actin filament bundle assembly	28/2061	105/18723	6.21e-06	2.30e-04	28
GO:00300388	Lung	IAC	contractile actin filament bundle assembly	28/2061	106/18723	7.56e-06	2.64e-04	28
GO:00431498	Lung	IAC	stress fiber assembly	28/2061	106/18723	7.56e-06	2.64e-04	28

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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

GNL1

SNV

Missense_Mutation

novel

c.775N>T

p.Arg259Trp

p.R259W

P36915

protein_coding

deleterious(0.02)

possibly_damaging(0.446)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

GNL1

insertion

In_Frame_Ins

novel

c.1469_1470insTTCTCTCCTCTTCTCCCTTCTTTTTTCATGCATTCT

p.Thr490_Ala491insSerLeuLeuPheSerLeuLeuPheSerCysIleLeu

p.T490_A491insSLLFSLLFSCIL

P36915

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

GNL1

insertion

Nonsense_Mutation

novel

c.1381_1382insTGTTCAGCAATCTGCACATAGGAAGTTGAATGAATGGATGAATG

p.His461LeufsTer10

p.H461Lfs*10

P36915

protein_coding

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

GNL1

insertion

Frame_Shift_Ins

novel

c.540_541insGGACCGAGACATCCAGAGCAATC

p.Leu181GlyfsTer13

p.L181Gfs*13

P36915

protein_coding

TCGA-A8-A08B-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

GNL1

SNV

Missense_Mutation

rs758752898

c.904G>A

p.Val302Met

p.V302M

P36915

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GNL1

SNV

Missense_Mutation

novel

c.775C>T

p.Arg259Trp

p.R259W

P36915

protein_coding

deleterious(0.02)

possibly_damaging(0.446)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GNL1

SNV

Missense_Mutation

c.1438N>A

p.Glu480Lys

p.E480K

P36915

protein_coding

deleterious(0.01)

benign(0.054)

TCGA-C5-A7CM-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GNL1

SNV

Missense_Mutation

c.494C>T

p.Ser165Phe

p.S165F

P36915

protein_coding

deleterious(0.04)

benign(0.037)

TCGA-DR-A0ZM-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unspecific

Cisplatin

GNL1

SNV

Missense_Mutation

c.449G>A

p.Arg150Gln

p.R150Q

P36915

protein_coding

tolerated(0.18)

benign(0.029)

TCGA-AA-3494-01

Colorectum

colon adenocarcinoma

Male

<65

III/IV

Chemotherapy

folinic

GNL1

SNV

Missense_Mutation

rs757866378

c.824N>A

p.Arg275Gln

p.R275Q

P36915

protein_coding

deleterious(0.01)

benign(0.278)

TCGA-AA-3966-01

Colorectum

colon adenocarcinoma

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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