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:00226139	Breast	Precancer	ribonucleoprotein complex biogenesis	79/1080	463/18723	2.11e-18	1.03e-15	79
GO:00971939	Breast	Precancer	intrinsic apoptotic signaling pathway	59/1080	288/18723	8.07e-18	3.60e-15	59
GO:20012339	Breast	Precancer	regulation of apoptotic signaling pathway	65/1080	356/18723	7.70e-17	3.17e-14	65
GO:20012429	Breast	Precancer	regulation of intrinsic apoptotic signaling pathway	41/1080	164/18723	6.48e-16	2.31e-13	41
GO:00718269	Breast	Precancer	ribonucleoprotein complex subunit organization	48/1080	227/18723	2.68e-15	8.45e-13	48
GO:00226189	Breast	Precancer	ribonucleoprotein complex assembly	47/1080	220/18723	3.47e-15	1.03e-12	47
GO:00069799	Breast	Precancer	response to oxidative stress	70/1080	446/18723	1.59e-14	4.26e-12	70
GO:00525479	Breast	Precancer	regulation of peptidase activity	71/1080	461/18723	2.72e-14	6.94e-12	71
GO:00525489	Breast	Precancer	regulation of endopeptidase activity	67/1080	432/18723	1.06e-13	2.36e-11	67
GO:00083809	Breast	Precancer	RNA splicing	65/1080	434/18723	1.27e-12	2.53e-10	65
GO:00362939	Breast	Precancer	response to decreased oxygen levels	53/1080	322/18723	4.09e-12	6.84e-10	53
GO:00016669	Breast	Precancer	response to hypoxia	51/1080	307/18723	7.33e-12	1.11e-09	51
GO:00704829	Breast	Precancer	response to oxygen levels	55/1080	347/18723	7.47e-12	1.11e-09	55
GO:20001169	Breast	Precancer	regulation of cysteine-type endopeptidase activity	43/1080	235/18723	1.30e-11	1.83e-09	43
GO:00068398	Breast	Precancer	mitochondrial transport	45/1080	254/18723	1.37e-11	1.88e-09	45
GO:00432819	Breast	Precancer	regulation of cysteine-type endopeptidase activity involved in apoptotic process	40/1080	209/18723	1.59e-11	2.07e-09	40
GO:00003759	Breast	Precancer	RNA splicing, via transesterification reactions	52/1080	324/18723	1.74e-11	2.22e-09	52
GO:00003779	Breast	Precancer	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	51/1080	320/18723	3.55e-11	4.04e-09	51
GO:00003989	Breast	Precancer	mRNA splicing, via spliceosome	51/1080	320/18723	3.55e-11	4.04e-09	51
GO:00621979	Breast	Precancer	cellular response to chemical stress	51/1080	337/18723	2.40e-10	2.34e-08	51

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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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