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: NONO

Gene summary for NONO

Gene summary.

Gene information	Species	Human
	Gene symbol	NONO
	Gene ID	4841
	Gene name	non-POU domain containing octamer binding
	Gene Alias	MRXS34
	Cytomap	Xq13.1
	Gene Type	protein-coding
	GO ID	GO:0002218
	UniProtAcc	A0A0S2Z4Z9

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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
4841	NONO	HTA11_3410_2000001011	Human	Colorectum	AD	1.23e-13	4.33e-01	0.0155
4841	NONO	HTA11_2487_2000001011	Human	Colorectum	SER	9.46e-03	4.21e-01	-0.1808
4841	NONO	HTA11_2951_2000001011	Human	Colorectum	AD	4.35e-06	6.96e-01	0.0216
4841	NONO	HTA11_1938_2000001011	Human	Colorectum	AD	4.14e-12	7.21e-01	-0.0811
4841	NONO	HTA11_78_2000001011	Human	Colorectum	AD	1.23e-15	5.48e-01	-0.1088
4841	NONO	HTA11_347_2000001011	Human	Colorectum	AD	1.65e-21	7.20e-01	-0.1954
4841	NONO	HTA11_411_2000001011	Human	Colorectum	SER	2.90e-02	7.13e-01	-0.2602
4841	NONO	HTA11_83_2000001011	Human	Colorectum	SER	1.13e-02	2.55e-01	-0.1526
4841	NONO	HTA11_696_2000001011	Human	Colorectum	AD	1.05e-15	5.04e-01	-0.1464
4841	NONO	HTA11_866_2000001011	Human	Colorectum	AD	3.72e-06	3.65e-01	-0.1001
4841	NONO	HTA11_1391_2000001011	Human	Colorectum	AD	3.04e-24	9.97e-01	-0.059
4841	NONO	HTA11_546_2000001011	Human	Colorectum	AD	5.56e-10	6.28e-01	-0.0842
4841	NONO	HTA11_7862_2000001011	Human	Colorectum	AD	9.41e-12	7.72e-01	-0.0179
4841	NONO	HTA11_866_3004761011	Human	Colorectum	AD	3.85e-39	1.18e+00	0.096
4841	NONO	HTA11_4255_2000001011	Human	Colorectum	SER	3.21e-07	7.89e-01	0.0446
4841	NONO	HTA11_8622_2000001021	Human	Colorectum	SER	2.25e-11	9.43e-01	0.0528
4841	NONO	HTA11_7663_2000001011	Human	Colorectum	SER	9.88e-12	9.21e-01	0.0131
4841	NONO	HTA11_10623_2000001011	Human	Colorectum	AD	1.22e-08	7.20e-01	-0.0177
4841	NONO	HTA11_6801_2000001011	Human	Colorectum	SER	3.65e-14	1.17e+00	0.0171
4841	NONO	HTA11_10711_2000001011	Human	Colorectum	AD	2.80e-07	5.53e-01	0.0338

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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
Prostate		BPH: Benign Prostatic Hyperplasia
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:19032042	Colorectum	MSS	negative regulation of oxidative stress-induced neuron death	9/3467	19/18723	3.88e-03	2.83e-02	9
GO:19012152	Colorectum	MSS	negative regulation of neuron death	53/3467	208/18723	7.60e-03	4.77e-02	53
GO:00083803	Colorectum	MSI-H	RNA splicing	82/1319	434/18723	1.22e-16	4.53e-14	82
GO:20012423	Colorectum	MSI-H	regulation of intrinsic apoptotic signaling pathway	40/1319	164/18723	2.39e-12	4.91e-10	40
GO:20012333	Colorectum	MSI-H	regulation of apoptotic signaling pathway	61/1319	356/18723	7.62e-11	1.37e-08	61
GO:00971933	Colorectum	MSI-H	intrinsic apoptotic signaling pathway	52/1319	288/18723	2.82e-10	4.23e-08	52
GO:00069793	Colorectum	MSI-H	response to oxidative stress	68/1319	446/18723	1.17e-09	1.59e-07	68
GO:20012343	Colorectum	MSI-H	negative regulation of apoptotic signaling pathway	41/1319	224/18723	1.43e-08	1.69e-06	41
GO:00621973	Colorectum	MSI-H	cellular response to chemical stress	51/1319	337/18723	1.78e-07	1.52e-05	51
GO:20012433	Colorectum	MSI-H	negative regulation of intrinsic apoptotic signaling pathway	23/1319	98/18723	2.29e-07	1.93e-05	23
GO:19021753	Colorectum	MSI-H	regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	12/1319	29/18723	2.39e-07	1.95e-05	12
GO:19032013	Colorectum	MSI-H	regulation of oxidative stress-induced cell death	19/1319	74/18723	5.79e-07	4.28e-05	19
GO:00364733	Colorectum	MSI-H	cell death in response to oxidative stress	21/1319	95/18723	2.16e-06	1.33e-04	21
GO:00345993	Colorectum	MSI-H	cellular response to oxidative stress	43/1319	288/18723	2.31e-06	1.40e-04	43
GO:19004073	Colorectum	MSI-H	regulation of cellular response to oxidative stress	20/1319	89/18723	2.86e-06	1.62e-04	20
GO:00086313	Colorectum	MSI-H	intrinsic apoptotic signaling pathway in response to oxidative stress	13/1319	45/18723	8.62e-06	4.16e-04	13
GO:19028823	Colorectum	MSI-H	regulation of response to oxidative stress	20/1319	98/18723	1.34e-05	6.06e-04	20
GO:19032043	Colorectum	MSI-H	negative regulation of oxidative stress-induced neuron death	7/1319	19/18723	2.01e-04	5.31e-03	7
GO:19032021	Colorectum	MSI-H	negative regulation of oxidative stress-induced cell death	12/1319	53/18723	2.53e-04	6.54e-03	12
GO:19021763	Colorectum	MSI-H	negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	7/1319	20/18723	2.90e-04	7.17e-03	7

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
NONO	STM	Liver	Cirrhotic	MFSD9,HNRNPU,LCMT1, etc.	4.68e-01

∗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

NONO

SNV

Missense_Mutation

c.292N>A

p.Gly98Arg

p.G98R

Q15233

protein_coding

deleterious(0.01)

possibly_damaging(0.768)

TCGA-A2-A259-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

NONO

SNV

Missense_Mutation

c.911N>A

p.Arg304His

p.R304H

Q15233

protein_coding

tolerated(0.39)

benign(0.003)

TCGA-D8-A1JN-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozolum

NONO

SNV

Missense_Mutation

novel

c.1081G>A

p.Glu361Lys

p.E361K

Q15233

protein_coding

deleterious(0)

possibly_damaging(0.587)

TCGA-EW-A1J5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NONO

insertion

Frame_Shift_Ins

novel

c.853_854insA

p.Val285AspfsTer10

p.V285Dfs*10

Q15233

protein_coding

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

NONO

insertion

In_Frame_Ins

novel

c.854_855insCTC

p.Val285_Asp286insSer

p.V285_D286insS

Q15233

protein_coding

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

NONO

insertion

Frame_Shift_Ins

novel

c.1405_1406insACTTTAAGGGGGTGACATATATGTCTTACTTA

p.Arg469HisfsTer26

p.R469Hfs*26

Q15233

protein_coding

TCGA-A7-A0D9-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

NONO

deletion

Frame_Shift_Del

c.1268delG

p.Gly423GlufsTer5

p.G423Efs*5

Q15233

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

NONO

SNV

Missense_Mutation

novel

c.523N>C

p.Glu175Gln

p.E175Q

Q15233

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-C5-A8XJ-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

NONO

SNV

Missense_Mutation

novel

c.265N>A

p.Glu89Lys

p.E89K

Q15233

protein_coding

deleterious(0)

benign(0.021)

TCGA-EX-A8YF-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NONO

SNV

Missense_Mutation

c.694N>C

p.Asp232His

p.D232H

Q15233

protein_coding

deleterious(0)

probably_damaging(0.985)

TCGA-LP-A4AV-01

Cervix

cervical & endocervical cancer

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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