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: CBFB

Gene summary for CBFB

Gene summary.

Gene information	Species	Human
	Gene symbol	CBFB
	Gene ID	865
	Gene name	core-binding factor subunit beta
	Gene Alias	PEBP2B
	Cytomap	16q22.1
	Gene Type	protein-coding
	GO ID	GO:0000122
	UniProtAcc	A0A024R6X2

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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
865	CBFB	CCI_1	Human	Cervix	CC	6.67e-03	5.28e-01	0.528
865	CBFB	CCI_2	Human	Cervix	CC	2.20e-05	6.97e-01	0.5249
865	CBFB	LZE4T	Human	Esophagus	ESCC	4.29e-05	3.48e-02	0.0811
865	CBFB	LZE7T	Human	Esophagus	ESCC	1.16e-03	1.23e-01	0.0667
865	CBFB	LZE8T	Human	Esophagus	ESCC	4.54e-04	-1.07e-02	0.067
865	CBFB	LZE20T	Human	Esophagus	ESCC	5.80e-04	3.03e-02	0.0662
865	CBFB	LZE22T	Human	Esophagus	ESCC	8.45e-05	1.58e-01	0.068
865	CBFB	LZE24T	Human	Esophagus	ESCC	4.47e-10	1.64e-01	0.0596
865	CBFB	P1T-E	Human	Esophagus	ESCC	7.31e-06	1.87e-01	0.0875
865	CBFB	P2T-E	Human	Esophagus	ESCC	3.29e-15	2.68e-01	0.1177
865	CBFB	P4T-E	Human	Esophagus	ESCC	1.90e-27	4.76e-01	0.1323
865	CBFB	P5T-E	Human	Esophagus	ESCC	5.24e-16	2.06e-01	0.1327
865	CBFB	P8T-E	Human	Esophagus	ESCC	1.80e-16	2.36e-01	0.0889
865	CBFB	P9T-E	Human	Esophagus	ESCC	4.47e-09	4.99e-02	0.1131
865	CBFB	P10T-E	Human	Esophagus	ESCC	6.40e-09	7.55e-02	0.116
865	CBFB	P11T-E	Human	Esophagus	ESCC	2.34e-09	3.00e-01	0.1426
865	CBFB	P12T-E	Human	Esophagus	ESCC	4.42e-13	1.07e-01	0.1122
865	CBFB	P15T-E	Human	Esophagus	ESCC	2.09e-16	1.22e-01	0.1149
865	CBFB	P16T-E	Human	Esophagus	ESCC	9.49e-14	1.34e-01	0.1153
865	CBFB	P17T-E	Human	Esophagus	ESCC	6.56e-04	2.23e-01	0.1278

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
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:190370813	Oral cavity	EOLP	positive regulation of hemopoiesis	34/2218	157/18723	3.32e-04	3.08e-03	34
GO:00508681	Oral cavity	EOLP	negative regulation of T cell activation	28/2218	122/18723	4.03e-04	3.58e-03	28
GO:0046638	Oral cavity	EOLP	positive regulation of alpha-beta T cell differentiation	15/2218	50/18723	4.75e-04	4.16e-03	15
GO:000150322	Oral cavity	EOLP	ossification	70/2218	408/18723	8.89e-04	6.81e-03	70
GO:0046636	Oral cavity	EOLP	negative regulation of alpha-beta T cell activation	13/2218	43/18723	1.03e-03	7.63e-03	13
GO:00456203	Oral cavity	EOLP	negative regulation of lymphocyte differentiation	15/2218	55/18723	1.42e-03	9.62e-03	15
GO:0046639	Oral cavity	EOLP	negative regulation of alpha-beta T cell differentiation	9/2218	26/18723	2.14e-03	1.34e-02	9
GO:00456212	Oral cavity	EOLP	positive regulation of lymphocyte differentiation	23/2218	104/18723	2.14e-03	1.34e-02	23
GO:00455811	Oral cavity	EOLP	negative regulation of T cell differentiation	13/2218	47/18723	2.52e-03	1.53e-02	13
GO:0043371	Oral cavity	EOLP	negative regulation of CD4-positive, alpha-beta T cell differentiation	8/2218	22/18723	2.64e-03	1.59e-02	8
GO:2000515	Oral cavity	EOLP	negative regulation of CD4-positive, alpha-beta T cell activation	10/2218	32/18723	2.93e-03	1.72e-02	10
GO:0043374	Oral cavity	EOLP	CD8-positive, alpha-beta T cell differentiation	6/2218	14/18723	3.54e-03	2.01e-02	6
GO:00455822	Oral cavity	EOLP	positive regulation of T cell differentiation	20/2218	91/18723	4.35e-03	2.37e-02	20
GO:000164922	Oral cavity	EOLP	osteoblast differentiation	41/2218	229/18723	4.47e-03	2.42e-02	41
GO:20011851	Oral cavity	EOLP	regulation of CD8-positive, alpha-beta T cell activation	7/2218	19/18723	4.48e-03	2.42e-02	7
GO:0036037	Oral cavity	EOLP	CD8-positive, alpha-beta T cell activation	8/2218	27/18723	1.07e-02	4.75e-02	8
GO:003009932	Oral cavity	NEOLP	myeloid cell differentiation	83/2005	381/18723	1.79e-10	1.69e-08	83
GO:004578532	Oral cavity	NEOLP	positive regulation of cell adhesion	88/2005	437/18723	3.28e-09	1.95e-07	88
GO:000150331	Oral cavity	NEOLP	ossification	81/2005	408/18723	2.67e-08	1.15e-06	81
GO:000020931	Oral cavity	NEOLP	protein polyubiquitination	53/2005	236/18723	1.22e-07	4.38e-06	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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
CBFB	BMEM	Liver	HCC	MAL,IKZF1,PCNA, etc.	6.44e-02
CBFB	TREG	Liver	HCC	MAL,IKZF1,PCNA, etc.	8.06e-02
CBFB	TFH	Liver	Healthy	MAL,IKZF1,PCNA, etc.	3.71e-01
CBFB	CD8TEREX	Lung	IAC	BCL2,KLRC3,GRAP2, etc.	7.89e-02
CBFB	CD8TEXP	Lung	IAC	BCL2,KLRC3,GRAP2, etc.	1.57e-01
CBFB	SMC	Oral cavity	ADJ	COL13A1,KPNA2,PLA2G15, etc.	2.35e-01
CBFB	LC	Skin	ADJ	HCAR2,SLC27A3,EGOT, etc.	3.75e-01
CBFB	M1MAC	Skin	ADJ	HCAR2,SLC27A3,EGOT, etc.	6.01e-02
CBFB	LC	Skin	cSCC	HCAR2,SLC27A3,EGOT, etc.	2.90e-01
CBFB	cDC	Skin	cSCC	HCAR2,SLC27A3,EGOT, etc.	1.38e-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

CBFB

SNV

Missense_Mutation

c.394N>A

p.Ala132Thr

p.A132T

Q13951

protein_coding

deleterious(0)

probably_damaging(0.989)

TCGA-A2-A0EO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

CBFB

SNV

Missense_Mutation

c.201N>T

p.Gln67His

p.Q67H

Q13951

protein_coding

tolerated(0.55)

probably_damaging(0.962)

TCGA-A8-A08S-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

CBFB

SNV

Missense_Mutation

novel

c.220N>A

p.Gln74Lys

p.Q74K

Q13951

protein_coding

tolerated(0.74)

benign(0.031)

TCGA-A8-A08T-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CBFB

SNV

Missense_Mutation

c.362N>A

p.Gly121Asp

p.G121D

Q13951

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-A8-A096-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CBFB

SNV

Missense_Mutation

c.188A>T

p.Asn63Ile

p.N63I

Q13951

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-AC-A3QQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CBFB

SNV

Missense_Mutation

c.296N>T

p.Ala99Val

p.A99V

Q13951

protein_coding

tolerated(0.16)

probably_damaging(0.961)

TCGA-B6-A0RN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CBFB

SNV

Missense_Mutation

c.311N>G

p.Asn104Ser

p.N104S

Q13951

protein_coding

deleterious(0)

possibly_damaging(0.819)

TCGA-BH-A0EA-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

CBFB

SNV

Missense_Mutation

c.306N>G

p.Ile102Met

p.I102M

Q13951

protein_coding

deleterious(0)

probably_damaging(0.944)

TCGA-BH-A1FL-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CBFB

SNV

Missense_Mutation

c.104N>C

p.Arg35Pro

p.R35P

Q13951

protein_coding

deleterious(0)

benign(0.01)

TCGA-E2-A15C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

arimidex

CBFB

SNV

Missense_Mutation

c.167N>G

p.Ala56Gly

p.A56G

Q13951

protein_coding

deleterious(0.01)

probably_damaging(0.966)

TCGA-E2-A1L9-01

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
865	CBFB	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		CYTARABINE HYDROCHLORIDE	CYTARABINE HYDROCHLORIDE
865	CBFB	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		PURPUROGALLIN	PURPUROGALLIN
865	CBFB	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		PHENANTHROLINE	PHENANTHROLINE
865	CBFB	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		CY-208243	CHEMBL313737
865	CBFB	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		FUSARIC ACID	FUSARIC ACID
865	CBFB	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		PYROGALLOL	PYROGALLOL
865	CBFB	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		APOMORPHINE HYDROCHLORIDE HEMIHYDRATE	APOMORPHINE HYDROCHLORIDE HEMIHYDRATE
865	CBFB	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		QUINOLINIC ACID	QUINOLINIC ACID
865	CBFB	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		L-NOREPINEPHRINE	L-NOREPINEPHRINE
865	CBFB	CLINICALLY ACTIONABLE, TRANSCRIPTION FACTOR		IRIGINOL HEXAACEATATE	IRIGINOL HEXAACEATATE

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