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: NFATC1

Gene summary for NFATC1

Gene summary.

Gene information	Species	Human
	Gene symbol	NFATC1
	Gene ID	4772
	Gene name	nuclear factor of activated T cells 1
	Gene Alias	NF-ATC
	Cytomap	18q23
	Gene Type	protein-coding
	GO ID	GO:0001816
	UniProtAcc	O95644

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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
4772	NFATC1	LZE24T	Human	Esophagus	ESCC	4.50e-03	2.49e-01	0.0596
4772	NFATC1	P1T-E	Human	Esophagus	ESCC	4.00e-05	2.95e-01	0.0875
4772	NFATC1	P2T-E	Human	Esophagus	ESCC	9.17e-38	7.34e-01	0.1177
4772	NFATC1	P4T-E	Human	Esophagus	ESCC	8.74e-07	1.99e-01	0.1323
4772	NFATC1	P8T-E	Human	Esophagus	ESCC	4.78e-06	4.84e-02	0.0889
4772	NFATC1	P9T-E	Human	Esophagus	ESCC	1.71e-02	1.91e-01	0.1131
4772	NFATC1	P10T-E	Human	Esophagus	ESCC	2.59e-05	1.32e-01	0.116
4772	NFATC1	P11T-E	Human	Esophagus	ESCC	8.61e-06	3.28e-01	0.1426
4772	NFATC1	P12T-E	Human	Esophagus	ESCC	1.49e-12	3.66e-01	0.1122
4772	NFATC1	P15T-E	Human	Esophagus	ESCC	5.32e-05	1.87e-01	0.1149
4772	NFATC1	P16T-E	Human	Esophagus	ESCC	5.58e-32	6.45e-01	0.1153
4772	NFATC1	P20T-E	Human	Esophagus	ESCC	6.98e-14	5.35e-01	0.1124
4772	NFATC1	P21T-E	Human	Esophagus	ESCC	1.61e-09	3.51e-01	0.1617
4772	NFATC1	P22T-E	Human	Esophagus	ESCC	8.64e-07	1.27e-01	0.1236
4772	NFATC1	P23T-E	Human	Esophagus	ESCC	3.96e-12	3.93e-01	0.108
4772	NFATC1	P24T-E	Human	Esophagus	ESCC	1.26e-03	1.08e-01	0.1287
4772	NFATC1	P26T-E	Human	Esophagus	ESCC	7.04e-18	4.69e-01	0.1276
4772	NFATC1	P27T-E	Human	Esophagus	ESCC	4.13e-03	1.84e-01	0.1055
4772	NFATC1	P28T-E	Human	Esophagus	ESCC	7.37e-26	6.94e-01	0.1149
4772	NFATC1	P30T-E	Human	Esophagus	ESCC	3.27e-12	5.03e-01	0.137

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma

∗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:001605517	Esophagus	ESCC	Wnt signaling pathway	268/8552	444/18723	2.32e-10	6.58e-09	268
GO:019873817	Esophagus	ESCC	cell-cell signaling by wnt	269/8552	446/18723	2.41e-10	6.79e-09	269
GO:003011117	Esophagus	ESCC	regulation of Wnt signaling pathway	194/8552	328/18723	5.39e-07	7.14e-06	194
GO:00301788	Esophagus	ESCC	negative regulation of Wnt signaling pathway	97/8552	170/18723	1.81e-03	8.31e-03	97
GO:00031793	Esophagus	ESCC	heart valve morphogenesis	34/8552	55/18723	1.16e-02	3.90e-02	34
GO:00031703	Esophagus	ESCC	heart valve development	39/8552	65/18723	1.41e-02	4.59e-02	39
GO:001605510	Oral cavity	OSCC	Wnt signaling pathway	227/7305	444/18723	1.10e-07	1.87e-06	227
GO:019873810	Oral cavity	OSCC	cell-cell signaling by wnt	227/7305	446/18723	1.75e-07	2.86e-06	227
GO:003011110	Oral cavity	OSCC	regulation of Wnt signaling pathway	165/7305	328/18723	1.87e-05	1.80e-04	165
GO:00331733	Oral cavity	OSCC	calcineurin-NFAT signaling cascade	26/7305	43/18723	3.55e-03	1.49e-02	26
GO:00426927	Oral cavity	OSCC	muscle cell differentiation	175/7305	384/18723	4.79e-03	1.92e-02	175
GO:00480164	Oral cavity	OSCC	inositol phosphate-mediated signaling	30/7305	55/18723	1.39e-02	4.59e-02	30
GO:001605515	Oral cavity	LP	Wnt signaling pathway	140/4623	444/18723	5.80e-04	5.35e-03	140
GO:019873815	Oral cavity	LP	cell-cell signaling by wnt	140/4623	446/18723	7.12e-04	6.38e-03	140
GO:003011115	Oral cavity	LP	regulation of Wnt signaling pathway	103/4623	328/18723	3.29e-03	2.21e-02	103
GO:001605523	Oral cavity	EOLP	Wnt signaling pathway	89/2218	444/18723	3.66e-07	1.06e-05	89
GO:019873823	Oral cavity	EOLP	cell-cell signaling by wnt	89/2218	446/18723	4.49e-07	1.25e-05	89
GO:004269214	Oral cavity	EOLP	muscle cell differentiation	77/2218	384/18723	2.18e-06	4.91e-05	77
GO:003011123	Oral cavity	EOLP	regulation of Wnt signaling pathway	67/2218	328/18723	5.11e-06	1.04e-04	67
GO:00031702	Oral cavity	EOLP	heart valve development	18/2218	65/18723	4.03e-04	3.58e-03	18

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa05166211	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
hsa0421829	Esophagus	ESCC	Cellular senescence	119/4205	156/8465	5.89e-12	9.40e-11	4.81e-11	119
hsa05170210	Esophagus	ESCC	Human immunodeficiency virus 1 infection	147/4205	212/8465	3.37e-09	3.53e-08	1.81e-08	147
hsa05167211	Esophagus	ESCC	Kaposi sarcoma-associated herpesvirus infection	136/4205	194/8465	4.28e-09	4.22e-08	2.16e-08	136
hsa0513526	Esophagus	ESCC	Yersinia infection	100/4205	137/8465	1.80e-08	1.59e-07	8.12e-08	100
hsa05417211	Esophagus	ESCC	Lipid and atherosclerosis	143/4205	215/8465	3.30e-07	2.45e-06	1.26e-06	143
hsa05163210	Esophagus	ESCC	Human cytomegalovirus infection	148/4205	225/8465	5.73e-07	4.00e-06	2.05e-06	148
hsa0493310	Esophagus	ESCC	AGE-RAGE signaling pathway in diabetic complications	72/4205	100/8465	4.15e-06	2.28e-05	1.17e-05	72
hsa051619	Esophagus	ESCC	Hepatitis B	108/4205	162/8465	7.68e-06	4.15e-05	2.12e-05	108
hsa046259	Esophagus	ESCC	C-type lectin receptor signaling pathway	73/4205	104/8465	1.57e-05	7.98e-05	4.09e-05	73
hsa046599	Esophagus	ESCC	Th17 cell differentiation	68/4205	108/8465	3.53e-03	9.30e-03	4.76e-03	68
hsa046585	Esophagus	ESCC	Th1 and Th2 cell differentiation	58/4205	92/8465	6.49e-03	1.60e-02	8.19e-03	58
hsa046607	Esophagus	ESCC	T cell receptor signaling pathway	63/4205	104/8465	1.60e-02	3.60e-02	1.84e-02	63
hsa05166310	Esophagus	ESCC	Human T-cell leukemia virus 1 infection	164/4205	222/8465	8.13e-14	2.09e-12	1.07e-12	164
hsa0421838	Esophagus	ESCC	Cellular senescence	119/4205	156/8465	5.89e-12	9.40e-11	4.81e-11	119
hsa0517038	Esophagus	ESCC	Human immunodeficiency virus 1 infection	147/4205	212/8465	3.37e-09	3.53e-08	1.81e-08	147
hsa0516738	Esophagus	ESCC	Kaposi sarcoma-associated herpesvirus infection	136/4205	194/8465	4.28e-09	4.22e-08	2.16e-08	136
hsa05135111	Esophagus	ESCC	Yersinia infection	100/4205	137/8465	1.80e-08	1.59e-07	8.12e-08	100
hsa05417310	Esophagus	ESCC	Lipid and atherosclerosis	143/4205	215/8465	3.30e-07	2.45e-06	1.26e-06	143
hsa0516338	Esophagus	ESCC	Human cytomegalovirus infection	148/4205	225/8465	5.73e-07	4.00e-06	2.05e-06	148

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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
NFATC1	QUIE	Esophagus	LGIN	TRAF4,TGIF1,KDM6B, etc.	4.40e-01
NFATC1	NEUT	Pancreas	Healthy	AC018445.5,AL163541.1,TTBK2, etc.	1.03e-01
NFATC1	NEUT	Pancreas	PanIN	AC018445.5,AL163541.1,TTBK2, etc.	9.20e-02
NFATC1	MALTB	Pancreas	PDAC	AC018445.5,AL163541.1,TTBK2, etc.	1.67e-01
NFATC1	BAS	Prostate	Healthy	LMNA,IL32,TWIST2, etc.	3.25e-01
NFATC1	M1MAC	Stomach	CAG	AC018445.5,ALDH1A1,CD40LG, etc.	1.88e-01
NFATC1	M1MAC	Stomach	Healthy	AC018445.5,ALDH1A1,CD40LG, etc.	7.09e-02
NFATC1	M1MAC	Stomach	SIM	AC018445.5,ALDH1A1,CD40LG, etc.	2.39e-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

NFATC1

SNV

Missense_Mutation

novel

c.1337G>A

p.Gly446Asp

p.G446D

O95644

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AR-A2LE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

NFATC1

SNV

Missense_Mutation

rs774191442

c.1696G>A

p.Val566Ile

p.V566I

O95644

protein_coding

deleterious(0.02)

probably_damaging(0.942)

TCGA-E2-A2P5-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

arimidex

NFATC1

SNV

Missense_Mutation

rs752605795

c.461C>T

p.Thr154Met

p.T154M

O95644

protein_coding

tolerated(0.15)

probably_damaging(0.971)

TCGA-OL-A66J-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NFATC1

SNV

Missense_Mutation

novel

c.2001N>C

p.Arg667Ser

p.R667S

O95644

protein_coding

tolerated(0.27)

possibly_damaging(0.843)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

NFATC1

SNV

Missense_Mutation

rs372492742

c.260N>T

p.Ser87Leu

p.S87L

O95644

protein_coding

tolerated(0.34)

benign(0.001)

TCGA-C5-A1BQ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

NFATC1

SNV

Missense_Mutation

novel

c.1508N>T

p.Ser503Phe

p.S503F

O95644

protein_coding

deleterious(0)

probably_damaging(0.973)

TCGA-C5-A2LZ-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Unknown

NFATC1

SNV

Missense_Mutation

rs372492742

c.260C>T

p.Ser87Leu

p.S87L

O95644

protein_coding

tolerated(0.34)

benign(0.001)

TCGA-C5-A3HL-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

NFATC1

SNV

Missense_Mutation

rs780214363

c.154N>A

p.Val52Ile

p.V52I

O95644

protein_coding

tolerated(0.38)

benign(0.003)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

NFATC1

SNV

Missense_Mutation

c.487N>A

p.Glu163Lys

p.E163K

O95644

protein_coding

deleterious(0.01)

possibly_damaging(0.601)

TCGA-IR-A3LA-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

NFATC1

SNV

Missense_Mutation

novel

c.2342C>T

p.Ala781Val

p.A781V

O95644

protein_coding

tolerated(0.13)

benign(0.053)

TCGA-VS-A9UJ-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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