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: CCT3

Gene summary for CCT3

Gene summary.

Gene information	Species	Human
	Gene symbol	CCT3
	Gene ID	7203
	Gene name	chaperonin containing TCP1 subunit 3
	Gene Alias	CCT-gamma
	Cytomap	1q22
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	B3KX11

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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
7203	CCT3	HTA11_3410_2000001011	Human	Colorectum	AD	4.31e-06	3.23e-01	0.0155
7203	CCT3	HTA11_2487_2000001011	Human	Colorectum	SER	2.24e-04	4.71e-01	-0.1808
7203	CCT3	HTA11_2951_2000001011	Human	Colorectum	AD	4.86e-02	5.58e-01	0.0216
7203	CCT3	HTA11_1938_2000001011	Human	Colorectum	AD	5.74e-17	7.87e-01	-0.0811
7203	CCT3	HTA11_78_2000001011	Human	Colorectum	AD	3.45e-08	5.31e-01	-0.1088
7203	CCT3	HTA11_347_2000001011	Human	Colorectum	AD	3.63e-20	6.57e-01	-0.1954
7203	CCT3	HTA11_3361_2000001011	Human	Colorectum	AD	4.45e-07	7.28e-01	-0.1207
7203	CCT3	HTA11_83_2000001011	Human	Colorectum	SER	3.90e-07	4.94e-01	-0.1526
7203	CCT3	HTA11_696_2000001011	Human	Colorectum	AD	7.49e-14	6.02e-01	-0.1464
7203	CCT3	HTA11_866_2000001011	Human	Colorectum	AD	2.40e-10	5.03e-01	-0.1001
7203	CCT3	HTA11_1391_2000001011	Human	Colorectum	AD	2.57e-29	1.25e+00	-0.059
7203	CCT3	HTA11_2992_2000001011	Human	Colorectum	SER	6.44e-05	7.46e-01	-0.1706
7203	CCT3	HTA11_5212_2000001011	Human	Colorectum	AD	1.37e-03	3.79e-01	-0.2061
7203	CCT3	HTA11_5216_2000001011	Human	Colorectum	SER	3.11e-04	6.53e-01	-0.1462
7203	CCT3	HTA11_546_2000001011	Human	Colorectum	AD	2.92e-06	5.60e-01	-0.0842
7203	CCT3	HTA11_7862_2000001011	Human	Colorectum	AD	2.18e-02	4.93e-01	-0.0179
7203	CCT3	HTA11_866_3004761011	Human	Colorectum	AD	2.93e-29	1.10e+00	0.096
7203	CCT3	HTA11_4255_2000001011	Human	Colorectum	SER	2.67e-02	6.16e-01	0.0446
7203	CCT3	HTA11_8622_2000001021	Human	Colorectum	SER	1.81e-04	5.50e-01	0.0528
7203	CCT3	HTA11_7663_2000001011	Human	Colorectum	SER	8.84e-05	6.63e-01	0.0131

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
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
Prostate		BPH: Benign Prostatic Hyperplasia
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:0071897	Colorectum	AD	DNA biosynthetic process	55/3918	180/18723	1.46e-03	1.24e-02	55
GO:1904358	Colorectum	AD	positive regulation of telomere maintenance via telomere lengthening	16/3918	37/18723	1.81e-03	1.49e-02	16
GO:1904356	Colorectum	AD	regulation of telomere maintenance via telomere lengthening	23/3918	61/18723	1.96e-03	1.58e-02	23
GO:0032212	Colorectum	AD	positive regulation of telomere maintenance via telomerase	15/3918	34/18723	1.96e-03	1.58e-02	15
GO:0007004	Colorectum	AD	telomere maintenance via telomerase	25/3918	69/18723	2.43e-03	1.88e-02	25
GO:0070198	Colorectum	AD	protein localization to chromosome, telomeric region	13/3918	29/18723	3.26e-03	2.39e-02	13
GO:0070202	Colorectum	AD	regulation of establishment of protein localization to chromosome	7/3918	12/18723	5.09e-03	3.38e-02	7
GO:1904851	Colorectum	AD	positive regulation of establishment of protein localization to telomere	6/3918	10/18723	8.03e-03	4.73e-02	6
GO:0006278	Colorectum	AD	RNA-dependent DNA biosynthetic process	25/3918	75/18723	8.36e-03	4.89e-02	25
GO:19038291	Colorectum	SER	positive regulation of cellular protein localization	86/2897	276/18723	3.61e-11	6.11e-09	86
GO:19049511	Colorectum	SER	positive regulation of establishment of protein localization	91/2897	319/18723	1.69e-09	1.68e-07	91
GO:00316471	Colorectum	SER	regulation of protein stability	86/2897	298/18723	2.56e-09	2.42e-07	86
GO:00725941	Colorectum	SER	establishment of protein localization to organelle	111/2897	422/18723	4.98e-09	4.49e-07	111
GO:19001801	Colorectum	SER	regulation of protein localization to nucleus	46/2897	136/18723	8.50e-08	5.27e-06	46
GO:00508211	Colorectum	SER	protein stabilization	58/2897	191/18723	1.46e-07	8.59e-06	58
GO:19001821	Colorectum	SER	positive regulation of protein localization to nucleus	33/2897	87/18723	2.81e-07	1.52e-05	33
GO:00345041	Colorectum	SER	protein localization to nucleus	74/2897	290/18723	5.74e-06	2.05e-04	74
GO:20002781	Colorectum	SER	regulation of DNA biosynthetic process	33/2897	106/18723	3.83e-05	9.82e-04	33
GO:00064031	Colorectum	SER	RNA localization	53/2897	201/18723	4.51e-05	1.13e-03	53
GO:00510541	Colorectum	SER	positive regulation of DNA metabolic process	53/2897	201/18723	4.51e-05	1.13e-03	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

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

CCT3

SNV

Missense_Mutation

novel

c.1345C>A

p.Arg449Ser

p.R449S

P49368

protein_coding

deleterious(0.04)

possibly_damaging(0.531)

TCGA-A7-A4SF-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

carboplatin

CCT3

SNV

Missense_Mutation

rs763340746

c.1535N>T

p.Thr512Met

p.T512M

P49368

protein_coding

deleterious(0)

probably_damaging(0.932)

TCGA-BH-A0EE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

CCT3

SNV

Missense_Mutation

c.773N>G

p.Ile258Ser

p.I258S

P49368

protein_coding

deleterious(0)

possibly_damaging(0.883)

TCGA-D8-A1X9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

adriamycin+cyclophosphamide

CCT3

SNV

Missense_Mutation

rs746245572

c.710N>A

p.Arg237His

p.R237H

P49368

protein_coding

deleterious(0)

possibly_damaging(0.803)

TCGA-D8-A1XT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin+cyclophosphamide

CCT3

SNV

Missense_Mutation

c.1447G>A

p.Glu483Lys

p.E483K

P49368

protein_coding

tolerated(0.47)

benign(0.013)

TCGA-EW-A1OV-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

epirubicin

CCT3

insertion

Nonsense_Mutation

novel

c.1227_1228insAAGACCTAACTTTATGGTTAG

p.Pro409_Gly410insLysThrTerLeuTyrGlyTer

p.P409_G410insKT*LYG*

P49368

protein_coding

TCGA-B6-A0RG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CCT3

insertion

Nonsense_Mutation

novel

c.1225_1226insTAGCATAATGGA

p.Pro409delinsLeuAlaTerTrpThr

p.P409delinsLA*WT

P49368

protein_coding

TCGA-B6-A0RG-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

CCT3

SNV

Missense_Mutation

rs375964353

c.688C>T

p.Arg230Trp

p.R230W

P49368

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-EA-A3HU-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CCT3

SNV

Missense_Mutation

rs373870763

c.1567G>A

p.Val523Ile

p.V523I

P49368

protein_coding

tolerated(0.29)

possibly_damaging(0.546)

TCGA-AA-3864-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

CCT3

SNV

Missense_Mutation

novel

c.59G>T

p.Arg20Ile

p.R20I

P49368

protein_coding

deleterious(0)

possibly_damaging(0.786)

TCGA-AA-A00N-01

Colorectum

colon adenocarcinoma

Male

>=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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