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: NSUN2

Gene summary for NSUN2

Gene summary.

Gene information	Species	Human
	Gene symbol	NSUN2
	Gene ID	54888
	Gene name	NOP2/Sun RNA methyltransferase 2
	Gene Alias	MISU
	Cytomap	5p15.31
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q08J23

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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
54888	NSUN2	P127T-E	Human	Esophagus	ESCC	7.86e-23	2.51e-01	0.0826
54888	NSUN2	P128T-E	Human	Esophagus	ESCC	1.40e-56	1.92e+00	0.1241
54888	NSUN2	P130T-E	Human	Esophagus	ESCC	6.59e-73	1.39e+00	0.1676
54888	NSUN2	NAFLD1	Human	Liver	NAFLD	3.21e-02	3.52e-01	-0.04
54888	NSUN2	HCC1_Meng	Human	Liver	HCC	5.32e-44	1.75e-03	0.0246
54888	NSUN2	HCC2_Meng	Human	Liver	HCC	3.65e-07	-2.83e-02	0.0107
54888	NSUN2	HCC1	Human	Liver	HCC	1.37e-10	3.53e+00	0.5336
54888	NSUN2	HCC2	Human	Liver	HCC	9.77e-13	3.14e+00	0.5341
54888	NSUN2	S014	Human	Liver	HCC	1.54e-21	8.15e-01	0.2254
54888	NSUN2	S015	Human	Liver	HCC	5.18e-14	7.97e-01	0.2375
54888	NSUN2	S016	Human	Liver	HCC	3.44e-18	7.09e-01	0.2243
54888	NSUN2	S027	Human	Liver	HCC	2.25e-06	7.19e-01	0.2446
54888	NSUN2	S028	Human	Liver	HCC	1.28e-17	9.69e-01	0.2503
54888	NSUN2	S029	Human	Liver	HCC	6.07e-14	9.27e-01	0.2581
54888	NSUN2	RNA-P17T-P17T-2	Human	Lung	IAC	9.76e-07	9.51e-01	0.3371
54888	NSUN2	RNA-P17T-P17T-4	Human	Lung	IAC	2.97e-07	9.74e-01	0.343
54888	NSUN2	C04	Human	Oral cavity	OSCC	9.79e-21	9.15e-01	0.2633
54888	NSUN2	C21	Human	Oral cavity	OSCC	5.95e-24	8.25e-01	0.2678
54888	NSUN2	C30	Human	Oral cavity	OSCC	1.63e-34	1.36e+00	0.3055
54888	NSUN2	C38	Human	Oral cavity	OSCC	3.14e-06	7.48e-01	0.172

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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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:0009895	Colorectum	AD	negative regulation of catabolic process	124/3918	320/18723	1.66e-13	3.35e-11	124
GO:0031330	Colorectum	AD	negative regulation of cellular catabolic process	104/3918	262/18723	2.66e-12	3.96e-10	104
GO:0006401	Colorectum	AD	RNA catabolic process	102/3918	278/18723	8.64e-10	6.76e-08	102
GO:0044270	Colorectum	AD	cellular nitrogen compound catabolic process	147/3918	451/18723	3.35e-09	2.23e-07	147
GO:0046700	Colorectum	AD	heterocycle catabolic process	145/3918	445/18723	4.37e-09	2.84e-07	145
GO:0034655	Colorectum	AD	nucleobase-containing compound catabolic process	133/3918	407/18723	1.56e-08	9.12e-07	133
GO:0019439	Colorectum	AD	aromatic compound catabolic process	146/3918	467/18723	7.48e-08	3.84e-06	146
GO:1901361	Colorectum	AD	organic cyclic compound catabolic process	153/3918	495/18723	8.23e-08	4.18e-06	153
GO:0006913	Colorectum	AD	nucleocytoplasmic transport	102/3918	301/18723	1.00e-07	4.85e-06	102
GO:0051169	Colorectum	AD	nuclear transport	102/3918	301/18723	1.00e-07	4.85e-06	102
GO:0032386	Colorectum	AD	regulation of intracellular transport	109/3918	337/18723	5.33e-07	1.95e-05	109
GO:0043487	Colorectum	AD	regulation of RNA stability	63/3918	170/18723	9.17e-07	3.12e-05	63
GO:0006403	Colorectum	AD	RNA localization	71/3918	201/18723	1.54e-06	4.76e-05	71
GO:0051236	Colorectum	AD	establishment of RNA localization	58/3918	166/18723	1.95e-05	4.01e-04	58
GO:0015931	Colorectum	AD	nucleobase-containing compound transport	73/3918	222/18723	2.02e-05	4.10e-04	73
GO:0046822	Colorectum	AD	regulation of nucleocytoplasmic transport	41/3918	106/18723	2.17e-05	4.33e-04	41
GO:0050657	Colorectum	AD	nucleic acid transport	57/3918	163/18723	2.22e-05	4.39e-04	57
GO:0050658	Colorectum	AD	RNA transport	57/3918	163/18723	2.22e-05	4.39e-04	57
GO:0001701	Colorectum	AD	in utero embryonic development	110/3918	367/18723	2.36e-05	4.62e-04	110
GO:0051168	Colorectum	AD	nuclear export	53/3918	154/18723	6.89e-05	1.11e-03	53

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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

NSUN2

SNV

Missense_Mutation

c.1876N>A

p.Asp626Asn

p.D626N

Q08J23

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A2-A0CR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NSUN2

SNV

Missense_Mutation

rs745927756

c.658N>T

p.Arg220Cys

p.R220C

Q08J23

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NSUN2

SNV

Missense_Mutation

novel

c.2117N>G

p.Val706Gly

p.V706G

Q08J23

protein_coding

deleterious(0.01)

benign(0.141)

TCGA-AO-A1KP-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

fluorouracil

NSUN2

SNV

Missense_Mutation

rs759251595

c.2008N>T

p.Ala670Ser

p.A670S

Q08J23

protein_coding

tolerated(0.76)

benign(0.02)

TCGA-E9-A2JS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cyclophosphamide

NSUN2

insertion

Nonsense_Mutation

novel

c.1617_1618insTTTCATCTTATTTTTTTACTTACAGGTTATTAACACA

p.Asp540PhefsTer11

p.D540Ffs*11

Q08J23

protein_coding

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

NSUN2

deletion

Frame_Shift_Del

novel

c.403delN

p.Ile135SerfsTer2

p.I135Sfs*2

Q08J23

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

NSUN2

SNV

Missense_Mutation

rs746142475

c.2167G>A

p.Ala723Thr

p.A723T

Q08J23

protein_coding

tolerated(0.19)

benign(0.003)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NSUN2

SNV

Missense_Mutation

novel

c.259G>A

p.Ala87Thr

p.A87T

Q08J23

protein_coding

deleterious(0.04)

possibly_damaging(0.616)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NSUN2

SNV

Missense_Mutation

c.178N>A

p.Glu60Lys

p.E60K

Q08J23

protein_coding

deleterious(0.01)

benign(0.091)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

NSUN2

SNV

Missense_Mutation

novel

c.2001N>G

p.Asn667Lys

p.N667K

Q08J23

protein_coding

tolerated(0.93)

benign(0)

TCGA-VS-A8EK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

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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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