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: NANS

Gene summary for NANS

Gene summary.

Gene information	Species	Human
	Gene symbol	NANS
	Gene ID	54187
	Gene name	N-acetylneuraminate synthase
	Gene Alias	HEL-S-100
	Cytomap	9q22.33
	Gene Type	protein-coding
	GO ID	GO:0005975
	UniProtAcc	Q9NR45

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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
54187	NANS	GSM4909281	Human	Breast	IDC	1.61e-02	2.77e-01	0.21
54187	NANS	GSM4909282	Human	Breast	IDC	1.71e-03	3.36e-01	-0.0288
54187	NANS	GSM4909285	Human	Breast	IDC	2.30e-04	2.91e-01	0.21
54187	NANS	GSM4909296	Human	Breast	IDC	8.90e-06	3.12e-01	0.1524
54187	NANS	GSM4909297	Human	Breast	IDC	2.18e-10	-1.44e-01	0.1517
54187	NANS	GSM4909311	Human	Breast	IDC	4.81e-18	-2.00e-02	0.1534
54187	NANS	GSM4909312	Human	Breast	IDC	2.57e-03	2.23e-01	0.1552
54187	NANS	GSM4909316	Human	Breast	IDC	5.49e-07	5.03e-01	0.21
54187	NANS	GSM4909319	Human	Breast	IDC	1.37e-20	-1.53e-01	0.1563
54187	NANS	GSM4909320	Human	Breast	IDC	2.96e-02	5.24e-03	0.1575
54187	NANS	GSM4909321	Human	Breast	IDC	4.47e-06	1.15e-01	0.1559
54187	NANS	brca1	Human	Breast	Precancer	1.49e-03	2.98e-01	-0.0338
54187	NANS	brca2	Human	Breast	Precancer	1.31e-03	2.58e-01	-0.024
54187	NANS	brca3	Human	Breast	Precancer	9.09e-05	2.51e-01	-0.0263
54187	NANS	NCCBC5	Human	Breast	DCIS	2.93e-04	6.69e-02	0.2046
54187	NANS	P1	Human	Breast	IDC	3.26e-07	-7.14e-02	0.1527
54187	NANS	P2	Human	Breast	IDC	1.13e-09	5.25e-01	0.21
54187	NANS	DCIS2	Human	Breast	DCIS	6.12e-49	1.23e-01	0.0085
54187	NANS	HTA11_347_2000001011	Human	Colorectum	AD	4.79e-20	8.06e-01	-0.1954
54187	NANS	HTA11_411_2000001011	Human	Colorectum	SER	2.69e-05	8.53e-01	-0.2602

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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
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:0009225	Colorectum	AD	nucleotide-sugar metabolic process	16/3918	36/18723	1.27e-03	1.12e-02	16
GO:0070085	Colorectum	AD	glycosylation	67/3918	240/18723	5.78e-03	3.67e-02	67
GO:00092251	Colorectum	SER	nucleotide-sugar metabolic process	12/2897	36/18723	6.11e-03	4.42e-02	12
GO:00700851	Colorectum	FAP	glycosylation	50/2622	240/18723	2.30e-03	1.85e-02	50
GO:00092253	Colorectum	CRC	nucleotide-sugar metabolic process	10/2078	36/18723	4.68e-03	3.62e-02	10
GO:00700854	Esophagus	ESCC	glycosylation	144/8552	240/18723	5.12e-06	5.38e-05	144
GO:00092256	Esophagus	ESCC	nucleotide-sugar metabolic process	29/8552	36/18723	1.91e-05	1.67e-04	29
GO:00160514	Esophagus	ESCC	carbohydrate biosynthetic process	117/8552	202/18723	2.96e-04	1.79e-03	117
GO:00092262	Esophagus	ESCC	nucleotide-sugar biosynthetic process	14/8552	19/18723	1.27e-02	4.21e-02	14
GO:00160511	Liver	Cirrhotic	carbohydrate biosynthetic process	73/4634	202/18723	1.91e-04	1.77e-03	73
GO:00160512	Liver	HCC	carbohydrate biosynthetic process	113/7958	202/18723	7.64e-05	6.83e-04	113
GO:00700852	Liver	HCC	glycosylation	128/7958	240/18723	4.35e-04	2.92e-03	128
GO:00092254	Liver	HCC	nucleotide-sugar metabolic process	25/7958	36/18723	9.87e-04	5.71e-03	25
GO:00092255	Oral cavity	OSCC	nucleotide-sugar metabolic process	26/7305	36/18723	5.44e-05	4.51e-04	26
GO:00700853	Oral cavity	OSCC	glycosylation	117/7305	240/18723	1.29e-03	6.42e-03	117
GO:00092261	Oral cavity	OSCC	nucleotide-sugar biosynthetic process	14/7305	19/18723	2.31e-03	1.02e-02	14
GO:00160513	Oral cavity	OSCC	carbohydrate biosynthetic process	97/7305	202/18723	5.50e-03	2.13e-02	97
GO:007008511	Oral cavity	LP	glycosylation	77/4623	240/18723	5.60e-03	3.38e-02	77
GO:0009226	Prostate	Tumor	nucleotide-sugar biosynthetic process	8/3246	19/18723	1.00e-02	4.20e-02	8
GO:00092257	Thyroid	PTC	nucleotide-sugar metabolic process	23/5968	36/18723	7.78e-05	6.66e-04	23

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa01250	Colorectum	FAP	Biosynthesis of nucleotide sugars	13/1404	37/8465	4.79e-03	1.91e-02	1.16e-02	13
hsa012501	Colorectum	FAP	Biosynthesis of nucleotide sugars	13/1404	37/8465	4.79e-03	1.91e-02	1.16e-02	13
hsa012502	Colorectum	CRC	Biosynthesis of nucleotide sugars	12/1091	37/8465	1.66e-03	1.20e-02	8.16e-03	12
hsa012503	Colorectum	CRC	Biosynthesis of nucleotide sugars	12/1091	37/8465	1.66e-03	1.20e-02	8.16e-03	12
hsa012505	Esophagus	ESCC	Biosynthesis of nucleotide sugars	28/4205	37/8465	1.10e-03	3.42e-03	1.75e-03	28
hsa005202	Esophagus	ESCC	Amino sugar and nucleotide sugar metabolism	35/4205	49/8465	1.60e-03	4.88e-03	2.50e-03	35
hsa0125012	Esophagus	ESCC	Biosynthesis of nucleotide sugars	28/4205	37/8465	1.10e-03	3.42e-03	1.75e-03	28
hsa0052011	Esophagus	ESCC	Amino sugar and nucleotide sugar metabolism	35/4205	49/8465	1.60e-03	4.88e-03	2.50e-03	35
hsa00520	Oral cavity	OSCC	Amino sugar and nucleotide sugar metabolism	34/3704	49/8465	2.48e-04	8.08e-04	4.11e-04	34
hsa012504	Oral cavity	OSCC	Biosynthesis of nucleotide sugars	25/3704	37/8465	2.93e-03	7.49e-03	3.81e-03	25
hsa005201	Oral cavity	OSCC	Amino sugar and nucleotide sugar metabolism	34/3704	49/8465	2.48e-04	8.08e-04	4.11e-04	34
hsa0125011	Oral cavity	OSCC	Biosynthesis of nucleotide sugars	25/3704	37/8465	2.93e-03	7.49e-03	3.81e-03	25

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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

NANS

SNV

Missense_Mutation

rs770189007

c.919N>G

p.Leu307Val

p.L307V

Q9NR45

protein_coding

deleterious(0.03)

possibly_damaging(0.725)

TCGA-BH-A0B6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

NANS

deletion

Frame_Shift_Del

novel

c.943delN

p.Lys315ArgfsTer16

p.K315Rfs*16

Q9NR45

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

NANS

insertion

Nonsense_Mutation

novel

c.338_339insAACTTAGCA

p.Gly113_Met114insThrTerHis

p.G113_M114insT*H

Q9NR45

protein_coding

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

NANS

SNV

Missense_Mutation

novel

c.1066N>C

p.Lys356Gln

p.K356Q

Q9NR45

protein_coding

deleterious_low_confidence(0.01)

benign(0.044)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

NANS

SNV

Missense_Mutation

novel

c.535N>C

p.Phe179Leu

p.F179L

Q9NR45

protein_coding

tolerated(0.28)

benign(0.048)

TCGA-AG-A01J-01

Colorectum

rectum adenocarcinoma

Female

<65

I/II

Unknown

NANS

SNV

Missense_Mutation

novel

c.444N>C

p.Lys148Asn

p.K148N

Q9NR45

protein_coding

tolerated(0.12)

benign(0.021)

TCGA-EI-6917-01

Colorectum

rectum adenocarcinoma

Male

<65

III/IV

Chemotherapy

5fluorouracil+oxaciplatina+l-folinian

NANS

SNV

Missense_Mutation

novel

c.922N>G

p.Thr308Ala

p.T308A

Q9NR45

protein_coding

tolerated(0.32)

benign(0.015)

TCGA-A5-A0G2-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Unknown

NANS

SNV

Missense_Mutation

c.1016T>C

p.Val339Ala

p.V339A

Q9NR45

protein_coding

tolerated(0.07)

benign(0.287)

TCGA-A5-A0GP-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NANS

SNV

Missense_Mutation

novel

c.739N>A

p.Gly247Arg

p.G247R

Q9NR45

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A5-A1OF-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

NANS

SNV

Missense_Mutation

rs766705810

c.304N>A

p.Ala102Thr

p.A102T

Q9NR45

protein_coding

deleterious(0.01)

possibly_damaging(0.819)

TCGA-AP-A0LM-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

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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