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: MVP

Gene summary for MVP

Gene summary.

Gene information	Species	Human
	Gene symbol	MVP
	Gene ID	9961
	Gene name	major vault protein
	Gene Alias	LRP
	Cytomap	16p11.2
	Gene Type	protein-coding
	GO ID	GO:0001932
	UniProtAcc	Q14764

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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
9961	MVP	A015-C-203	Human	Colorectum	FAP	1.10e-19	-1.23e-01	-0.1294
9961	MVP	A015-C-204	Human	Colorectum	FAP	9.48e-08	-3.03e-01	-0.0228
9961	MVP	A014-C-040	Human	Colorectum	FAP	1.90e-02	-3.42e-01	-0.1184
9961	MVP	A002-C-201	Human	Colorectum	FAP	3.16e-09	-2.25e-01	0.0324
9961	MVP	A002-C-203	Human	Colorectum	FAP	2.95e-02	-1.39e-01	0.2786
9961	MVP	A001-C-119	Human	Colorectum	FAP	1.42e-08	-3.64e-01	-0.1557
9961	MVP	A001-C-108	Human	Colorectum	FAP	3.40e-12	-2.83e-01	-0.0272
9961	MVP	A002-C-205	Human	Colorectum	FAP	8.19e-17	-3.79e-01	-0.1236
9961	MVP	A001-C-104	Human	Colorectum	FAP	4.22e-07	-3.23e-01	0.0184
9961	MVP	A015-C-005	Human	Colorectum	FAP	8.82e-03	-1.74e-01	-0.0336
9961	MVP	A015-C-006	Human	Colorectum	FAP	1.40e-11	-3.05e-01	-0.0994
9961	MVP	A015-C-106	Human	Colorectum	FAP	3.38e-06	-1.99e-01	-0.0511
9961	MVP	A002-C-114	Human	Colorectum	FAP	3.74e-12	-1.77e-01	-0.1561
9961	MVP	A015-C-104	Human	Colorectum	FAP	2.98e-18	-2.34e-01	-0.1899
9961	MVP	A001-C-014	Human	Colorectum	FAP	2.62e-12	-2.84e-01	0.0135
9961	MVP	A002-C-016	Human	Colorectum	FAP	4.30e-15	-3.71e-01	0.0521
9961	MVP	A015-C-002	Human	Colorectum	FAP	1.03e-07	-3.15e-01	-0.0763
9961	MVP	A001-C-007	Human	Colorectum	CRC	2.54e-02	-3.65e-01	0.1899
9961	MVP	A001-C-203	Human	Colorectum	FAP	3.73e-09	-2.98e-01	-0.0481
9961	MVP	A002-C-116	Human	Colorectum	FAP	5.13e-19	-4.22e-01	-0.0452

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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
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:0038127	Colorectum	AD	ERBB signaling pathway	55/3918	121/18723	1.19e-09	8.85e-08	55
GO:0007173	Colorectum	AD	epidermal growth factor receptor signaling pathway	50/3918	108/18723	3.08e-09	2.07e-07	50
GO:0006403	Colorectum	AD	RNA localization	71/3918	201/18723	1.54e-06	4.76e-05	71
GO:1901185	Colorectum	AD	negative regulation of ERBB signaling pathway	19/3918	32/18723	2.39e-06	6.98e-05	19
GO:1901184	Colorectum	AD	regulation of ERBB signaling pathway	34/3918	79/18723	7.46e-06	1.82e-04	34
GO:0010563	Colorectum	AD	negative regulation of phosphorus metabolic process	130/3918	442/18723	1.26e-05	2.76e-04	130
GO:0045936	Colorectum	AD	negative regulation of phosphate metabolic process	129/3918	441/18723	1.81e-05	3.76e-04	129
GO:0051236	Colorectum	AD	establishment of RNA localization	58/3918	166/18723	1.95e-05	4.01e-04	58
GO:0015931	Colorectum	AD	nucleobase-containing compound transport	73/3918	222/18723	2.02e-05	4.10e-04	73
GO:0051348	Colorectum	AD	negative regulation of transferase activity	85/3918	268/18723	2.07e-05	4.19e-04	85
GO:0050657	Colorectum	AD	nucleic acid transport	57/3918	163/18723	2.22e-05	4.39e-04	57
GO:0050658	Colorectum	AD	RNA transport	57/3918	163/18723	2.22e-05	4.39e-04	57
GO:0046777	Colorectum	AD	protein autophosphorylation	74/3918	227/18723	2.48e-05	4.76e-04	74
GO:0042058	Colorectum	AD	regulation of epidermal growth factor receptor signaling pathway	31/3918	73/18723	2.56e-05	4.89e-04	31
GO:0042059	Colorectum	AD	negative regulation of epidermal growth factor receptor signaling pathway	16/3918	28/18723	2.96e-05	5.46e-04	16
GO:0042326	Colorectum	AD	negative regulation of phosphorylation	112/3918	385/18723	8.02e-05	1.27e-03	112
GO:0001933	Colorectum	AD	negative regulation of protein phosphorylation	101/3918	342/18723	9.39e-05	1.42e-03	101
GO:0006469	Colorectum	AD	negative regulation of protein kinase activity	65/3918	212/18723	5.21e-04	5.62e-03	65
GO:0033673	Colorectum	AD	negative regulation of kinase activity	71/3918	237/18723	6.18e-04	6.47e-03	71
GO:0051028	Colorectum	AD	mRNA transport	42/3918	130/18723	1.57e-03	1.32e-02	42

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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

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

MVP

SNV

Missense_Mutation

c.510G>C

p.Gln170His

p.Q170H

Q14764

protein_coding

tolerated(0.29)

benign(0.003)

TCGA-AR-A0TX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MVP

SNV

Missense_Mutation

c.1234G>A

p.Glu412Lys

p.E412K

Q14764

protein_coding

deleterious(0)

probably_damaging(0.952)

TCGA-C8-A3M7-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

MVP

insertion

Frame_Shift_Ins

novel

c.2374_2375insAAGGCCTTTTGCAATGGCTATTCCTGCTGCCCAGAAAGCT

p.Val792GlufsTer38

p.V792Efs*38

Q14764

protein_coding

TCGA-A8-A06P-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unspecific

MVP

insertion

Frame_Shift_Ins

novel

c.874_875insA

p.Gly292GlufsTer55

p.G292Efs*55

Q14764

protein_coding

TCGA-AO-A0JD-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

MVP

insertion

In_Frame_Ins

novel

c.875_876insCTCTTCCTTTGAGCCCCAGTTTCAGTT

p.Gly292_Lys293insSerSerPheGluProGlnPheGlnPhe

p.G292_K293insSSFEPQFQF

Q14764

protein_coding

TCGA-AO-A0JD-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

MVP

insertion

Frame_Shift_Ins

novel

c.2596_2597insAGGTGAGAGTTGGGGAAGGTGTGTTGGTTTCAGGA

p.Pro866GlnfsTer43

p.P866Qfs*43

Q14764

protein_coding

TCGA-BH-A0B4-01

Breast

breast invasive carcinoma

Male

>=65

III/IV

Hormone Therapy

tamoxiphen

MVP

insertion

Frame_Shift_Ins

rs778534743

c.1744dupG

p.Ala582GlyfsTer9

p.A582Gfs*9

Q14764

protein_coding

TCGA-BH-A0HX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adrimycin

MVP

SNV

Missense_Mutation

novel

c.2012C>T

p.Ala671Val

p.A671V

Q14764

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MVP

SNV

Missense_Mutation

novel

c.10N>A

p.Glu4Lys

p.E4K

Q14764

protein_coding

tolerated(0.15)

benign(0.08)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MVP

SNV

Missense_Mutation

c.2641N>G

p.Gln881Glu

p.Q881E

Q14764

protein_coding

tolerated_low_confidence(0.21)

benign(0)

TCGA-Q1-A5R2-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

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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