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: CBLB

Gene summary for CBLB

Gene summary.

Gene information	Species	Human
	Gene symbol	CBLB
	Gene ID	868
	Gene name	Cbl proto-oncogene B
	Gene Alias	Cbl-b
	Cytomap	3q13.11
	Gene Type	protein-coding
	GO ID	GO:0001775
	UniProtAcc	Q13191

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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
868	CBLB	CCI_2	Human	Cervix	CC	1.59e-04	7.81e-01	0.5249
868	CBLB	CCI_3	Human	Cervix	CC	6.32e-16	9.84e-01	0.516
868	CBLB	HTA11_5212_2000001011	Human	Colorectum	AD	5.04e-03	-6.00e-01	-0.2061
868	CBLB	HTA11_866_3004761011	Human	Colorectum	AD	1.65e-03	-3.32e-01	0.096
868	CBLB	HTA11_8622_2000001021	Human	Colorectum	SER	3.64e-02	-4.91e-01	0.0528
868	CBLB	HTA11_99999974143_84620	Human	Colorectum	MSS	4.40e-23	-6.20e-01	0.3005
868	CBLB	A002-C-010	Human	Colorectum	FAP	2.20e-03	1.31e-01	0.242
868	CBLB	A001-C-207	Human	Colorectum	FAP	8.74e-04	1.41e-01	0.1278
868	CBLB	A015-C-203	Human	Colorectum	FAP	1.50e-27	-2.52e-01	-0.1294
868	CBLB	A015-C-204	Human	Colorectum	FAP	1.34e-06	-2.13e-01	-0.0228
868	CBLB	A014-C-040	Human	Colorectum	FAP	5.84e-05	-2.28e-01	-0.1184
868	CBLB	A002-C-201	Human	Colorectum	FAP	3.42e-14	-2.35e-01	0.0324
868	CBLB	A002-C-203	Human	Colorectum	FAP	3.45e-03	-1.10e-03	0.2786
868	CBLB	A001-C-119	Human	Colorectum	FAP	6.83e-07	-4.03e-01	-0.1557
868	CBLB	A001-C-108	Human	Colorectum	FAP	4.53e-16	-2.54e-01	-0.0272
868	CBLB	A002-C-021	Human	Colorectum	FAP	4.58e-03	3.65e-01	0.1171
868	CBLB	A002-C-205	Human	Colorectum	FAP	7.28e-25	-3.41e-01	-0.1236
868	CBLB	A001-C-104	Human	Colorectum	FAP	1.95e-02	-7.98e-02	0.0184
868	CBLB	A015-C-006	Human	Colorectum	FAP	2.64e-18	-5.08e-01	-0.0994
868	CBLB	A015-C-106	Human	Colorectum	FAP	1.13e-10	-2.41e-01	-0.0511

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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
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:004217613	Lung	AIS	regulation of protein catabolic process	92/1849	391/18723	1.34e-15	3.91e-12	92
GO:000989613	Lung	AIS	positive regulation of catabolic process	103/1849	492/18723	9.59e-14	1.86e-10	103
GO:004573213	Lung	AIS	positive regulation of protein catabolic process	60/1849	231/18723	1.47e-12	2.14e-09	60
GO:190332013	Lung	AIS	regulation of protein modification by small protein conjugation or removal	55/1849	242/18723	2.75e-09	4.92e-07	55
GO:003139613	Lung	AIS	regulation of protein ubiquitination	46/1849	210/18723	1.71e-07	1.72e-05	46
GO:004308711	Lung	AIS	regulation of GTPase activity	65/1849	348/18723	3.35e-07	2.83e-05	65
GO:000717312	Lung	AIS	epidermal growth factor receptor signaling pathway	29/1849	108/18723	3.99e-07	3.23e-05	29
GO:003812712	Lung	AIS	ERBB signaling pathway	30/1849	121/18723	1.60e-06	9.91e-05	30
GO:004593613	Lung	AIS	negative regulation of phosphate metabolic process	75/1849	441/18723	1.93e-06	1.12e-04	75
GO:001056313	Lung	AIS	negative regulation of phosphorus metabolic process	75/1849	442/18723	2.11e-06	1.20e-04	75
GO:004232613	Lung	AIS	negative regulation of phosphorylation	65/1849	385/18723	1.17e-05	4.69e-04	65
GO:004205811	Lung	AIS	regulation of epidermal growth factor receptor signaling pathway	20/1849	73/18723	1.77e-05	6.17e-04	20
GO:005109813	Lung	AIS	regulation of binding	61/1849	363/18723	2.48e-05	8.06e-04	61
GO:000691313	Lung	AIS	nucleocytoplasmic transport	52/1849	301/18723	4.54e-05	1.34e-03	52
GO:005116913	Lung	AIS	nuclear transport	52/1849	301/18723	4.54e-05	1.34e-03	52
GO:000193313	Lung	AIS	negative regulation of protein phosphorylation	57/1849	342/18723	5.71e-05	1.60e-03	57
GO:190118411	Lung	AIS	regulation of ERBB signaling pathway	20/1849	79/18723	6.12e-05	1.67e-03	20
GO:004800811	Lung	AIS	platelet-derived growth factor receptor signaling pathway	16/1849	56/18723	6.89e-05	1.84e-03	16
GO:190118512	Lung	AIS	negative regulation of ERBB signaling pathway	11/1849	32/18723	1.53e-04	3.26e-03	11
GO:004205913	Lung	AIS	negative regulation of epidermal growth factor receptor signaling pathway	10/1849	28/18723	2.13e-04	4.35e-03	10

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0412014	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa0414418	Cervix	CC	Endocytosis	64/1267	251/8465	6.97e-06	6.10e-05	3.61e-05	64
hsa0401210	Cervix	CC	ErbB signaling pathway	28/1267	85/8465	2.40e-05	1.82e-04	1.08e-04	28
hsa046254	Cervix	CC	C-type lectin receptor signaling pathway	25/1267	104/8465	9.52e-03	2.94e-02	1.74e-02	25
hsa046604	Cervix	CC	T cell receptor signaling pathway	25/1267	104/8465	9.52e-03	2.94e-02	1.74e-02	25
hsa0412015	Cervix	CC	Ubiquitin mediated proteolysis	49/1267	142/8465	4.26e-09	7.68e-08	4.54e-08	49
hsa0414419	Cervix	CC	Endocytosis	64/1267	251/8465	6.97e-06	6.10e-05	3.61e-05	64
hsa0401213	Cervix	CC	ErbB signaling pathway	28/1267	85/8465	2.40e-05	1.82e-04	1.08e-04	28
hsa0462511	Cervix	CC	C-type lectin receptor signaling pathway	25/1267	104/8465	9.52e-03	2.94e-02	1.74e-02	25
hsa0466011	Cervix	CC	T cell receptor signaling pathway	25/1267	104/8465	9.52e-03	2.94e-02	1.74e-02	25
hsa04012	Colorectum	AD	ErbB signaling pathway	31/2092	85/8465	1.02e-02	3.91e-02	2.50e-02	31
hsa040121	Colorectum	AD	ErbB signaling pathway	31/2092	85/8465	1.02e-02	3.91e-02	2.50e-02	31
hsa041442	Colorectum	SER	Endocytosis	81/1580	251/8465	1.14e-07	2.36e-06	1.71e-06	81
hsa041202	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041443	Colorectum	SER	Endocytosis	81/1580	251/8465	1.14e-07	2.36e-06	1.71e-06	81
hsa041203	Colorectum	SER	Ubiquitin mediated proteolysis	39/1580	142/8465	6.18e-03	3.66e-02	2.66e-02	39
hsa041444	Colorectum	MSS	Endocytosis	102/1875	251/8465	1.85e-11	4.43e-10	2.71e-10	102
hsa041204	Colorectum	MSS	Ubiquitin mediated proteolysis	55/1875	142/8465	5.02e-06	6.00e-05	3.68e-05	55
hsa040122	Colorectum	MSS	ErbB signaling pathway	30/1875	85/8465	3.73e-03	1.67e-02	1.02e-02	30
hsa041445	Colorectum	MSS	Endocytosis	102/1875	251/8465	1.85e-11	4.43e-10	2.71e-10	102

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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

CBLB

SNV

Missense_Mutation

c.422G>A

p.Arg141Gln

p.R141Q

Q13191

protein_coding

deleterious(0.01)

probably_damaging(0.997)

TCGA-A7-A0CJ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

CBLB

SNV

Missense_Mutation

c.1753N>A

p.Asp585Asn

p.D585N

Q13191

protein_coding

tolerated_low_confidence(0.06)

benign(0.001)

TCGA-A8-A09Q-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Hormone Therapy

anastrozole

CBLB

SNV

Missense_Mutation

rs748390313

c.2200N>T

p.Arg734Trp

p.R734W

Q13191

protein_coding

tolerated_low_confidence(0.06)

probably_damaging(0.936)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CBLB

SNV

Missense_Mutation

novel

c.68N>G

p.Leu23Trp

p.L23W

Q13191

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.994)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CBLB

SNV

Missense_Mutation

c.229N>G

p.Ile77Val

p.I77V

Q13191

protein_coding

deleterious(0.02)

possibly_damaging(0.876)

TCGA-AO-A03L-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

CBLB

SNV

Missense_Mutation

c.769C>T

p.His257Tyr

p.H257Y

Q13191

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-AR-A251-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

CBLB

SNV

Missense_Mutation

c.952N>G

p.Gln318Glu

p.Q318E

Q13191

protein_coding

deleterious(0)

possibly_damaging(0.833)

TCGA-B6-A0IK-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CBLB

SNV

Missense_Mutation

c.1210G>A

p.Asp404Asn

p.D404N

Q13191

protein_coding

deleterious(0.04)

probably_damaging(0.95)

TCGA-BH-A0B5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

CBLB

SNV

Missense_Mutation

c.2483C>T

p.Ala828Val

p.A828V

Q13191

protein_coding

tolerated_low_confidence(0.4)

benign(0.116)

TCGA-BH-A0C1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

CBLB

SNV

Missense_Mutation

c.1073N>G

p.Glu358Gly

p.E358G

Q13191

protein_coding

deleterious(0)

benign(0.241)

TCGA-BH-A0DK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

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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
868	CBLB	CLINICALLY ACTIONABLE, ENZYME		Fasudil	FASUDIL	26177294
868	CBLB	CLINICALLY ACTIONABLE, ENZYME		Fluorouracil	FLUOROURACIL	24351824

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