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: NOL3

Gene summary for NOL3

Gene summary.

Gene information	Species	Human
	Gene symbol	NOL3
	Gene ID	8996
	Gene name	nucleolar protein 3
	Gene Alias	ARC
	Cytomap	16q22.1
	Gene Type	protein-coding
	GO ID	GO:0000245
	UniProtAcc	O60936

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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
8996	NOL3	GSM4909291	Human	Breast	IDC	6.77e-06	3.74e-01	0.1753
8996	NOL3	GSM4909296	Human	Breast	IDC	3.20e-05	2.85e-01	0.1524
8996	NOL3	GSM4909311	Human	Breast	IDC	8.04e-07	4.59e-02	0.1534
8996	NOL3	GSM4909315	Human	Breast	IDC	7.07e-20	5.64e-01	0.21
8996	NOL3	GSM4909316	Human	Breast	IDC	2.12e-08	5.93e-01	0.21
8996	NOL3	GSM4909319	Human	Breast	IDC	1.27e-07	7.76e-02	0.1563
8996	NOL3	GSM4909321	Human	Breast	IDC	4.22e-23	6.18e-01	0.1559
8996	NOL3	brca3	Human	Breast	Precancer	2.98e-09	2.94e-01	-0.0263
8996	NOL3	DCIS2	Human	Breast	DCIS	3.91e-37	1.58e-01	0.0085
8996	NOL3	LZE4T	Human	Esophagus	ESCC	1.66e-17	5.18e-01	0.0811
8996	NOL3	LZE5T	Human	Esophagus	ESCC	4.79e-04	4.39e-01	0.0514
8996	NOL3	LZE7T	Human	Esophagus	ESCC	3.06e-09	5.68e-01	0.0667
8996	NOL3	LZE8T	Human	Esophagus	ESCC	1.16e-05	2.24e-01	0.067
8996	NOL3	LZE20T	Human	Esophagus	ESCC	1.80e-07	2.80e-01	0.0662
8996	NOL3	LZE22D1	Human	Esophagus	HGIN	2.26e-05	2.40e-01	0.0595
8996	NOL3	LZE24T	Human	Esophagus	ESCC	7.21e-04	1.26e-01	0.0596
8996	NOL3	LZE21T	Human	Esophagus	ESCC	2.22e-03	2.93e-01	0.0655
8996	NOL3	P1T-E	Human	Esophagus	ESCC	2.49e-15	5.62e-01	0.0875
8996	NOL3	P2T-E	Human	Esophagus	ESCC	7.69e-11	2.73e-01	0.1177
8996	NOL3	P4T-E	Human	Esophagus	ESCC	2.52e-33	7.94e-01	0.1323

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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

∗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:007135618	Oral cavity	OSCC	cellular response to tumor necrosis factor	128/7305	229/18723	1.49e-07	2.49e-06	128
GO:00469028	Oral cavity	OSCC	regulation of mitochondrial membrane permeability	45/7305	63/18723	1.80e-07	2.92e-06	45
GO:004586120	Oral cavity	OSCC	negative regulation of proteolysis	181/7305	351/18723	1.01e-06	1.37e-05	181
GO:00019594	Oral cavity	OSCC	regulation of cytokine-mediated signaling pathway	87/7305	150/18723	1.82e-06	2.35e-05	87
GO:000863117	Oral cavity	OSCC	intrinsic apoptotic signaling pathway in response to oxidative stress	33/7305	45/18723	3.08e-06	3.72e-05	33
GO:00607594	Oral cavity	OSCC	regulation of response to cytokine stimulus	92/7305	162/18723	3.25e-06	3.90e-05	92
GO:200123720	Oral cavity	OSCC	negative regulation of extrinsic apoptotic signaling pathway	60/7305	97/18723	4.31e-06	4.98e-05	60
GO:00332099	Oral cavity	OSCC	tumor necrosis factor-mediated signaling pathway	61/7305	99/18723	4.31e-06	4.98e-05	61
GO:00164856	Oral cavity	OSCC	protein processing	121/7305	225/18723	4.56e-06	5.23e-05	121
GO:007145317	Oral cavity	OSCC	cellular response to oxygen levels	98/7305	177/18723	7.10e-06	7.75e-05	98
GO:00108239	Oral cavity	OSCC	negative regulation of mitochondrion organization	34/7305	49/18723	1.59e-05	1.59e-04	34
GO:00714569	Oral cavity	OSCC	cellular response to hypoxia	84/7305	151/18723	2.46e-05	2.30e-04	84
GO:003629417	Oral cavity	OSCC	cellular response to decreased oxygen levels	88/7305	161/18723	3.91e-05	3.43e-04	88
GO:190217518	Oral cavity	OSCC	regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	22/7305	29/18723	6.05e-05	4.95e-04	22
GO:00380614	Oral cavity	OSCC	NIK/NF-kappaB signaling	78/7305	143/18723	1.14e-04	8.35e-04	78
GO:0051259	Oral cavity	OSCC	protein complex oligomerization	121/7305	238/18723	1.29e-04	9.21e-04	121
GO:005134618	Oral cavity	OSCC	negative regulation of hydrolase activity	182/7305	379/18723	1.98e-04	1.32e-03	182
GO:00192214	Oral cavity	OSCC	cytokine-mediated signaling pathway	222/7305	472/18723	2.02e-04	1.35e-03	222
GO:00902016	Oral cavity	OSCC	negative regulation of release of cytochrome c from mitochondria	16/7305	20/18723	2.24e-04	1.46e-03	16
GO:001095117	Oral cavity	OSCC	negative regulation of endopeptidase activity	126/7305	252/18723	2.37e-04	1.54e-03	126

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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

NOL3

SNV

Missense_Mutation

c.343N>C

p.Asp115His

p.D115H

O60936

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.966)

TCGA-IR-A3LI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NOL3

SNV

Missense_Mutation

novel

c.60N>C

p.Gln20His

p.Q20H

O60936

protein_coding

benign(0.187)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NOL3

SNV

Missense_Mutation

novel

c.604G>A

p.Glu202Lys

p.E202K

O60936

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.516)

TCGA-XS-A8TJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NOL3

SNV

Missense_Mutation

novel

c.299N>T

p.Gly100Val

p.G100V

O60936

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.991)

TCGA-BG-A222-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NOL3

SNV

Missense_Mutation

rs528140604

c.635N>T

p.Pro212Leu

p.P212L

O60936

protein_coding

tolerated_low_confidence(0.31)

benign(0)

TCGA-DF-A2KN-01

Endometrium

uterine corpus endometrioid carcinoma

Female

Unknown

I/II

Unknown

NOL3

insertion

Frame_Shift_Ins

novel

c.190_191insC

p.Gly64AlafsTer52

p.G64Afs*52

O60936

protein_coding

TCGA-AP-A0LH-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

paclitaxel

NOL3

SNV

Missense_Mutation

novel

c.796G>A

p.Glu266Lys

p.E266K

O60936

protein_coding

deleterious_low_confidence(0)

benign(0.042)

TCGA-CV-7097-01

Oral cavity

head & neck squamous cell carcinoma

Male

<65

I/II

Unknown

NOL3

SNV

Missense_Mutation

c.514N>A

p.Pro172Thr

p.P172T

O60936

protein_coding

tolerated_low_confidence(0.08)

benign(0.025)

TCGA-D7-A4YY-01

Stomach

stomach adenocarcinoma

Male

<65

III/IV

Chemotherapy

5-fluorouracil

NOL3

SNV

Missense_Mutation

rs547594151

c.259G>A

p.Ala87Thr

p.A87T

O60936

protein_coding

tolerated_low_confidence(0.25)

benign(0.196)

TCGA-HU-A4G8-01

Stomach

stomach adenocarcinoma

Female

>=65

I/II

Chemotherapy

5-fluorouracil

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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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