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: NFIL3

Gene summary for NFIL3

Gene summary.

Gene information	Species	Human
	Gene symbol	NFIL3
	Gene ID	4783
	Gene name	nuclear factor, interleukin 3 regulated
	Gene Alias	E4BP4
	Cytomap	9q22.31
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	A0A024R241

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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
4783	NFIL3	GSM5353221_PA_PB2A_Pool_1_3_S25_L001	Human	Prostate	Tumor	1.97e-07	4.96e-01	0.1633
4783	NFIL3	GSM5353224_PA_PR5186_Pool_1_2_3_S27_L001	Human	Prostate	Tumor	3.02e-17	7.72e-01	0.1621
4783	NFIL3	GSM5353225_PA_PR5196-1_Pool_1_2_3_S53_L002	Human	Prostate	Tumor	5.55e-05	6.89e-01	0.1619
4783	NFIL3	GSM5353227_PA_PR5199-193K_Pool_1_2_3_S55_L002	Human	Prostate	Tumor	2.47e-04	4.63e-01	0.1602
4783	NFIL3	GSM5353236_PA_PR5251_T1_S7_L001	Human	Prostate	Tumor	1.98e-11	8.78e-01	0.1608
4783	NFIL3	GSM5353237_PA_PR5251_T2_S8_L001	Human	Prostate	Tumor	1.68e-04	6.26e-01	0.1622
4783	NFIL3	GSM5353240_PA_PR5254_T1_S15_L001	Human	Prostate	Tumor	1.16e-05	4.14e-01	0.1575
4783	NFIL3	GSM5353243_PA_PR5261_T1_S23_L002	Human	Prostate	Tumor	2.51e-11	6.30e-01	0.1545
4783	NFIL3	GSM5353244_PA_PR5261_T2_S24_L002	Human	Prostate	Tumor	2.02e-10	6.60e-01	0.1569

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease
Prostate		BPH: Benign Prostatic Hyperplasia

∗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:000762312	Liver	Cirrhotic	circadian rhythm	84/4634	210/18723	7.04e-07	1.50e-05	84
GO:004851111	Liver	Cirrhotic	rhythmic process	103/4634	298/18723	8.47e-05	9.19e-04	103
GO:00713532	Liver	Cirrhotic	cellular response to interleukin-4	17/4634	33/18723	8.32e-04	6.06e-03	17
GO:00706702	Liver	Cirrhotic	response to interleukin-4	17/4634	36/18723	2.82e-03	1.63e-02	17
GO:000762321	Liver	HCC	circadian rhythm	117/7958	210/18723	7.29e-05	6.54e-04	117
GO:004851121	Liver	HCC	rhythmic process	156/7958	298/18723	3.54e-04	2.46e-03	156
GO:007135311	Liver	HCC	cellular response to interleukin-4	21/7958	33/18723	1.16e-02	4.28e-02	21
GO:004851110	Prostate	BPH	rhythmic process	96/3107	298/18723	1.88e-11	1.31e-09	96
GO:000762310	Prostate	BPH	circadian rhythm	73/3107	210/18723	1.02e-10	6.02e-09	73
GO:19031315	Prostate	BPH	mononuclear cell differentiation	98/3107	426/18723	3.43e-04	2.55e-03	98
GO:00300982	Prostate	BPH	lymphocyte differentiation	83/3107	374/18723	2.76e-03	1.46e-02	83
GO:00713534	Prostate	BPH	cellular response to interleukin-4	12/3107	33/18723	4.90e-03	2.32e-02	12
GO:00706704	Prostate	BPH	response to interleukin-4	12/3107	36/18723	1.07e-02	4.45e-02	12
GO:004851115	Prostate	Tumor	rhythmic process	99/3246	298/18723	1.65e-11	1.21e-09	99
GO:000762315	Prostate	Tumor	circadian rhythm	75/3246	210/18723	1.09e-10	6.79e-09	75
GO:190313113	Prostate	Tumor	mononuclear cell differentiation	102/3246	426/18723	2.87e-04	2.32e-03	102
GO:003009811	Prostate	Tumor	lymphocyte differentiation	87/3246	374/18723	1.93e-03	1.12e-02	87
GO:007135312	Prostate	Tumor	cellular response to interleukin-4	13/3246	33/18723	2.26e-03	1.28e-02	13
GO:007067011	Prostate	Tumor	response to interleukin-4	13/3246	36/18723	5.47e-03	2.60e-02	13

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa047104	Prostate	BPH	Circadian rhythm	15/1718	34/8465	1.40e-03	5.85e-03	3.62e-03	15
hsa0471011	Prostate	BPH	Circadian rhythm	15/1718	34/8465	1.40e-03	5.85e-03	3.62e-03	15
hsa0471021	Prostate	Tumor	Circadian rhythm	14/1791	34/8465	6.44e-03	2.16e-02	1.34e-02	14
hsa0471031	Prostate	Tumor	Circadian rhythm	14/1791	34/8465	6.44e-03	2.16e-02	1.34e-02	14

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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
NFIL3	MON	Colorectum	MSS	EXT1,ZNF322,DHX34, etc.	5.09e-01
NFIL3	INMON	Lung	AAH	CYCS,CFP,FCN1, etc.	8.95e-02
NFIL3	INMON	Lung	ADJ	VCAN,S100A8,S100A12, etc.	2.37e-01
NFIL3	LC	Lung	ADJ	VCAN,S100A8,S100A12, etc.	2.09e-01
NFIL3	LC	Lung	IAC	S100A9,S100A8,AQP9, etc.	2.90e-01
NFIL3	INMON	Lung	IAC	S100A9,S100A8,AQP9, etc.	5.40e-02
NFIL3	NEUT	Lung	IAC	S100A9,S100A8,AQP9, etc.	4.74e-02
NFIL3	M1MAC	Lung	IAC	S100A9,S100A8,AQP9, etc.	1.63e-01
NFIL3	MVA	Lung	Healthy	EAF1,ETV5,EREG, etc.	7.49e-02
NFIL3	ACINAR	Pancreas	PDAC	VCAN,RRP12,NAMPT, etc.	2.25e-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

NFIL3

SNV

Missense_Mutation

novel

c.571N>C

p.Ser191Pro

p.S191P

Q16649

protein_coding

tolerated(0.08)

benign(0.067)

TCGA-A7-A0CE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NFIL3

SNV

Missense_Mutation

novel

c.1287N>T

p.Glu429Asp

p.E429D

Q16649

protein_coding

deleterious_low_confidence(0.01)

benign(0.006)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

NFIL3

SNV

Missense_Mutation

rs374204202

c.1352T>C

p.Ile451Thr

p.I451T

Q16649

protein_coding

deleterious_low_confidence(0.03)

benign(0.006)

TCGA-E2-A14R-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

NFIL3

SNV

Missense_Mutation

c.276N>C

p.Glu92Asp

p.E92D

Q16649

protein_coding

deleterious(0)

probably_damaging(0.978)

TCGA-EW-A1J5-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NFIL3

insertion

Nonsense_Mutation

novel

c.442_443insGATGGAGAAGACGAGCAACAGGTCCCCAAGGGCCCCATCC

p.Tyr148Ter

p.Y148*

Q16649

protein_coding

TCGA-A2-A0CT-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

cytoxan

NFIL3

insertion

In_Frame_Ins

novel

c.568_569insCAACTGTGGTTAAAG

p.Asp189_Val190insAlaThrValValLys

p.D189_V190insATVVK

Q16649

protein_coding

TCGA-A7-A0CE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NFIL3

insertion

In_Frame_Ins

novel

c.355_356insAGAGGT

p.Glu118_Leu119insGlnArg

p.E118_L119insQR

Q16649

protein_coding

TCGA-A7-A0CE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NFIL3

insertion

Frame_Shift_Ins

novel

c.353_354insAGCAGGGGATAGCAAACTTATCT

p.Leu119AlafsTer12

p.L119Afs*12

Q16649

protein_coding

TCGA-A7-A0CE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

NFIL3

insertion

Nonsense_Mutation

novel

c.314_315insTTGATAATGAATTTT

p.Leu105_Ile106insTer

p.L105_I106ins*

Q16649

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

NFIL3

insertion

Frame_Shift_Ins

novel

c.312_313insGTAGAAGC

p.Leu105ValfsTer4

p.L105Vfs*4

Q16649

protein_coding

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

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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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