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: BAG5

Gene summary for BAG5

Gene summary.

Gene information	Species	Human
	Gene symbol	BAG5
	Gene ID	9529
	Gene name	BAG cochaperone 5
	Gene Alias	BAG-5
	Cytomap	14q32.33
	Gene Type	protein-coding
	GO ID	GO:0006457
	UniProtAcc	A0A024R6M6

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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
9529	BAG5	LZE4T	Human	Esophagus	ESCC	3.55e-09	2.53e-01	0.0811
9529	BAG5	LZE7T	Human	Esophagus	ESCC	1.89e-03	1.46e-01	0.0667
9529	BAG5	LZE8T	Human	Esophagus	ESCC	1.17e-05	1.71e-02	0.067
9529	BAG5	LZE20T	Human	Esophagus	ESCC	2.68e-07	8.45e-02	0.0662
9529	BAG5	LZE24T	Human	Esophagus	ESCC	3.03e-12	4.02e-01	0.0596
9529	BAG5	LZE6T	Human	Esophagus	ESCC	9.62e-03	2.86e-02	0.0845
9529	BAG5	P1T-E	Human	Esophagus	ESCC	3.28e-03	1.78e-01	0.0875
9529	BAG5	P2T-E	Human	Esophagus	ESCC	1.13e-20	2.58e-01	0.1177
9529	BAG5	P4T-E	Human	Esophagus	ESCC	9.09e-16	4.40e-01	0.1323
9529	BAG5	P5T-E	Human	Esophagus	ESCC	3.96e-15	3.15e-01	0.1327
9529	BAG5	P8T-E	Human	Esophagus	ESCC	8.37e-16	3.43e-01	0.0889
9529	BAG5	P9T-E	Human	Esophagus	ESCC	1.26e-04	1.13e-01	0.1131
9529	BAG5	P10T-E	Human	Esophagus	ESCC	3.29e-61	1.25e+00	0.116
9529	BAG5	P11T-E	Human	Esophagus	ESCC	2.49e-09	2.65e-01	0.1426
9529	BAG5	P12T-E	Human	Esophagus	ESCC	1.25e-26	6.40e-01	0.1122
9529	BAG5	P15T-E	Human	Esophagus	ESCC	2.58e-26	6.03e-01	0.1149
9529	BAG5	P16T-E	Human	Esophagus	ESCC	9.41e-15	2.95e-01	0.1153
9529	BAG5	P17T-E	Human	Esophagus	ESCC	6.47e-14	2.97e-01	0.1278
9529	BAG5	P20T-E	Human	Esophagus	ESCC	6.63e-14	2.10e-01	0.1124
9529	BAG5	P21T-E	Human	Esophagus	ESCC	6.63e-15	2.12e-01	0.1617

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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
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:00324359	Oral cavity	OSCC	negative regulation of proteasomal ubiquitin-dependent protein catabolic process	26/7305	35/18723	2.40e-05	2.26e-04	26
GO:190305117	Oral cavity	OSCC	negative regulation of proteolysis involved in cellular protein catabolic process	41/7305	64/18723	4.31e-05	3.71e-04	41
GO:190217518	Oral cavity	OSCC	regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	22/7305	29/18723	6.05e-05	4.95e-04	22
GO:005144420	Oral cavity	OSCC	negative regulation of ubiquitin-protein transferase activity	16/7305	19/18723	7.05e-05	5.60e-04	16
GO:001097510	Oral cavity	OSCC	regulation of neuron projection development	210/7305	445/18723	2.35e-04	1.52e-03	210
GO:009008310	Oral cavity	OSCC	regulation of inclusion body assembly	14/7305	17/18723	3.31e-04	2.04e-03	14
GO:19017998	Oral cavity	OSCC	negative regulation of proteasomal protein catabolic process	31/7305	49/18723	5.04e-04	2.95e-03	31
GO:190217610	Oral cavity	OSCC	negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	15/7305	20/18723	1.19e-03	5.99e-03	15
GO:003647319	Oral cavity	OSCC	cell death in response to oxidative stress	52/7305	95/18723	1.33e-03	6.62e-03	52
GO:007084116	Oral cavity	OSCC	inclusion body assembly	17/7305	24/18723	1.59e-03	7.56e-03	17
GO:19033323	Oral cavity	OSCC	regulation of protein folding	10/7305	12/18723	2.25e-03	1.00e-02	10
GO:190040718	Oral cavity	OSCC	regulation of cellular response to oxidative stress	47/7305	89/18723	5.62e-03	2.17e-02	47
GO:190320118	Oral cavity	OSCC	regulation of oxidative stress-induced cell death	40/7305	74/18723	6.09e-03	2.30e-02	40
GO:00313458	Oral cavity	OSCC	negative regulation of cell projection organization	89/7305	186/18723	8.51e-03	3.09e-02	89
GO:190288218	Oral cavity	OSCC	regulation of response to oxidative stress	50/7305	98/18723	1.03e-02	3.53e-02	50
GO:001049828	Skin	cSCC	proteasomal protein catabolic process	243/4864	490/18723	7.85e-30	4.10e-27	243
GO:0006457111	Skin	cSCC	protein folding	131/4864	212/18723	2.96e-28	1.32e-25	131
GO:004217629	Skin	cSCC	regulation of protein catabolic process	198/4864	391/18723	6.03e-26	1.89e-23	198
GO:004316128	Skin	cSCC	proteasome-mediated ubiquitin-dependent protein catabolic process	205/4864	412/18723	1.46e-25	4.16e-23	205
GO:190336229	Skin	cSCC	regulation of cellular protein catabolic process	139/4864	255/18723	2.06e-22	4.17e-20	139

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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

BAG5

SNV

Missense_Mutation

c.349N>C

p.Glu117Gln

p.E117Q

Q9UL15

protein_coding

tolerated(0.48)

probably_damaging(0.951)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

BAG5

SNV

Missense_Mutation

novel

c.574N>T

p.His192Tyr

p.H192Y

Q9UL15

protein_coding

deleterious_low_confidence(0)

benign(0.003)

TCGA-PE-A5DE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

BAG5

SNV

Missense_Mutation

novel

c.977N>T

p.Arg326Ile

p.R326I

Q9UL15

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.667)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

BAG5

SNV

Missense_Mutation

c.981N>A

p.Met327Ile

p.M327I

Q9UL15

protein_coding

tolerated_low_confidence(0.12)

benign(0.083)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

BAG5

SNV

Missense_Mutation

novel

c.1057N>A

p.Gly353Ser

p.G353S

Q9UL15

protein_coding

tolerated(0.19)

benign(0.009)

TCGA-JX-A3Q0-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Unknown

BAG5

SNV

Missense_Mutation

c.981N>C

p.Met327Ile

p.M327I

Q9UL15

protein_coding

tolerated_low_confidence(0.12)

benign(0.083)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

BAG5

SNV

Missense_Mutation

c.81N>C

p.Trp27Cys

p.W27C

Q9UL15

protein_coding

deleterious_low_confidence(0)

benign(0.023)

TCGA-Q1-A73O-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

BAG5

SNV

Missense_Mutation

novel

c.1431N>G

p.Ser477Arg

p.S477R

Q9UL15

protein_coding

tolerated(0.07)

possibly_damaging(0.734)

TCGA-VS-A94Z-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

BAG5

insertion

Frame_Shift_Ins

novel

c.260_261insCT

p.Thr88Ter

p.T88*

Q9UL15

protein_coding

TCGA-LP-A7HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

BAG5

SNV

Missense_Mutation

c.1438N>A

p.Asp480Asn

p.D480N

Q9UL15

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AG-3892-01

Colorectum

rectum adenocarcinoma

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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