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: CASC3

Gene summary for CASC3

Gene summary.

Gene information	Species	Human
	Gene symbol	CASC3
	Gene ID	22794
	Gene name	CASC3 exon junction complex subunit
	Gene Alias	BTZ
	Cytomap	17q21.1
	Gene Type	protein-coding
	GO ID	GO:0000184
	UniProtAcc	O15234

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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
22794	CASC3	GSM4909286	Human	Breast	IDC	1.84e-03	1.71e-01	0.1081
22794	CASC3	GSM4909291	Human	Breast	IDC	8.29e-42	1.03e+00	0.1753
22794	CASC3	GSM4909292	Human	Breast	IDC	2.03e-30	1.31e+00	0.1236
22794	CASC3	GSM4909296	Human	Breast	IDC	2.21e-02	-1.57e-01	0.1524
22794	CASC3	GSM4909311	Human	Breast	IDC	9.11e-07	-1.72e-01	0.1534
22794	CASC3	GSM4909319	Human	Breast	IDC	3.61e-09	-1.40e-01	0.1563
22794	CASC3	NCCBC14	Human	Breast	DCIS	4.25e-37	9.93e-01	0.2021
22794	CASC3	NCCBC5	Human	Breast	DCIS	4.13e-09	2.06e-01	0.2046
22794	CASC3	P1	Human	Breast	IDC	1.19e-07	-6.75e-02	0.1527
22794	CASC3	P2	Human	Breast	IDC	2.47e-02	-4.42e-02	0.21
22794	CASC3	DCIS2	Human	Breast	DCIS	7.29e-31	1.57e-01	0.0085
22794	CASC3	LZE2T	Human	Esophagus	ESCC	3.08e-02	5.84e-01	0.082
22794	CASC3	LZE4T	Human	Esophagus	ESCC	2.63e-08	3.78e-01	0.0811
22794	CASC3	LZE7T	Human	Esophagus	ESCC	6.43e-04	5.20e-01	0.0667
22794	CASC3	LZE8T	Human	Esophagus	ESCC	3.94e-03	2.58e-02	0.067
22794	CASC3	LZE24T	Human	Esophagus	ESCC	7.67e-13	5.51e-01	0.0596
22794	CASC3	P1T-E	Human	Esophagus	ESCC	4.35e-10	6.86e-01	0.0875
22794	CASC3	P2T-E	Human	Esophagus	ESCC	4.28e-18	4.23e-01	0.1177
22794	CASC3	P4T-E	Human	Esophagus	ESCC	8.58e-18	5.06e-01	0.1323
22794	CASC3	P5T-E	Human	Esophagus	ESCC	4.66e-10	2.48e-01	0.1327

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Breast		IDC: Invasive ductal carcinoma
		DCIS: Ductal carcinoma in situ
		Precancer(BRCA1-mut): Precancerous lesion from BRCA1 mutation carriers
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:000838014	Breast	IDC	RNA splicing	73/1434	434/18723	1.27e-10	1.57e-08	73
GO:000037514	Breast	IDC	RNA splicing, via transesterification reactions	58/1434	324/18723	9.44e-10	9.58e-08	58
GO:000037714	Breast	IDC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	57/1434	320/18723	1.60e-09	1.49e-07	57
GO:000039814	Breast	IDC	mRNA splicing, via spliceosome	57/1434	320/18723	1.60e-09	1.49e-07	57
GO:000641714	Breast	IDC	regulation of translation	74/1434	468/18723	1.67e-09	1.53e-07	74
GO:000640113	Breast	IDC	RNA catabolic process	38/1434	278/18723	3.54e-04	5.16e-03	38
GO:000640213	Breast	IDC	mRNA catabolic process	33/1434	232/18723	4.12e-04	5.66e-03	33
GO:000095613	Breast	IDC	nuclear-transcribed mRNA catabolic process	18/1434	112/18723	2.09e-03	1.96e-02	18
GO:190136112	Breast	IDC	organic cyclic compound catabolic process	56/1434	495/18723	2.12e-03	1.99e-02	56
GO:004670012	Breast	IDC	heterocycle catabolic process	51/1434	445/18723	2.51e-03	2.25e-02	51
GO:000640313	Breast	IDC	RNA localization	27/1434	201/18723	3.04e-03	2.60e-02	27
GO:003465513	Breast	IDC	nucleobase-containing compound catabolic process	47/1434	407/18723	3.12e-03	2.63e-02	47
GO:004427012	Breast	IDC	cellular nitrogen compound catabolic process	50/1434	451/18723	5.29e-03	3.93e-02	50
GO:001943912	Breast	IDC	aromatic compound catabolic process	51/1434	467/18723	6.54e-03	4.59e-02	51
GO:000838024	Breast	DCIS	RNA splicing	73/1390	434/18723	3.05e-11	5.08e-09	73
GO:000037524	Breast	DCIS	RNA splicing, via transesterification reactions	58/1390	324/18723	2.89e-10	3.34e-08	58
GO:000037724	Breast	DCIS	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	57/1390	320/18723	5.01e-10	5.35e-08	57
GO:000039824	Breast	DCIS	mRNA splicing, via spliceosome	57/1390	320/18723	5.01e-10	5.35e-08	57
GO:000641724	Breast	DCIS	regulation of translation	72/1390	468/18723	2.46e-09	2.17e-07	72
GO:000640123	Breast	DCIS	RNA catabolic process	38/1390	278/18723	1.91e-04	3.08e-03	38

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0301321	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0301524	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa0301331	Esophagus	ESCC	Nucleocytoplasmic transport	89/4205	108/8465	1.20e-12	2.37e-11	1.21e-11	89
hsa0301534	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa03013	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa0301521	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa030131	Liver	HCC	Nucleocytoplasmic transport	81/4020	108/8465	4.28e-09	6.83e-08	3.80e-08	81
hsa0301531	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa030136	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa030158	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0301311	Oral cavity	OSCC	Nucleocytoplasmic transport	82/3704	108/8465	7.93e-12	1.33e-10	6.77e-11	82
hsa0301513	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75

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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

CASC3

SNV

Missense_Mutation

c.1370N>T

p.Ser457Phe

p.S457F

O15234

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.77)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CASC3

SNV

Missense_Mutation

rs748828823

c.1264G>A

p.Glu422Lys

p.E422K

O15234

protein_coding

tolerated_low_confidence(0.05)

benign(0.321)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

CASC3

SNV

Missense_Mutation

rs139973585

c.1013N>A

p.Arg338Gln

p.R338Q

O15234

protein_coding

tolerated_low_confidence(0.12)

benign(0.143)

TCGA-C5-A8YQ-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

CASC3

SNV

Missense_Mutation

novel

c.70G>A

p.Asp24Asn

p.D24N

O15234

protein_coding

deleterious_low_confidence(0.03)

benign(0.003)

TCGA-DS-A1OC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

gemcitabine

CASC3

SNV

Missense_Mutation

novel

c.71A>C

p.Asp24Ala

p.D24A

O15234

protein_coding

tolerated_low_confidence(0.3)

benign(0.039)

TCGA-DS-A1OC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

gemcitabine

CASC3

SNV

Missense_Mutation

novel

c.514G>A

p.Asp172Asn

p.D172N

O15234

protein_coding

deleterious(0)

probably_damaging(0.993)

TCGA-JW-A5VL-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CASC3

SNV

Missense_Mutation

c.1940C>G

p.Pro647Arg

p.P647R

O15234

protein_coding

tolerated_low_confidence(0.06)

probably_damaging(0.999)

TCGA-LP-A4AV-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CASC3

SNV

Missense_Mutation

novel

c.46G>A

p.Glu16Lys

p.E16K

O15234

protein_coding

deleterious_low_confidence(0.01)

benign(0.269)

TCGA-VS-A9UZ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

CASC3

insertion

Frame_Shift_Ins

novel

c.161_162insGATCCTTCTAAAT

p.Arg55IlefsTer23

p.R55Ifs*23

O15234

protein_coding

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

CASC3

insertion

Frame_Shift_Ins

novel

c.1054_1055insCGTTCCAGTTT

p.Arg352ProfsTer7

p.R352Pfs*7

O15234

protein_coding

TCGA-DS-A1OB-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

carboplatin

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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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