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: ASCC2

Gene summary for ASCC2

Gene summary.

Gene information	Species	Human
	Gene symbol	ASCC2
	Gene ID	84164
	Gene name	activating signal cointegrator 1 complex subunit 2
	Gene Alias	ASC1p100
	Cytomap	22q12.2
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	Q9H1I8

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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
84164	ASCC2	LZE4T	Human	Esophagus	ESCC	3.19e-13	3.61e-01	0.0811
84164	ASCC2	LZE7T	Human	Esophagus	ESCC	9.40e-09	4.73e-01	0.0667
84164	ASCC2	LZE8T	Human	Esophagus	ESCC	4.85e-07	1.81e-01	0.067
84164	ASCC2	LZE20T	Human	Esophagus	ESCC	2.87e-08	3.08e-01	0.0662
84164	ASCC2	LZE21D1	Human	Esophagus	HGIN	1.59e-02	3.00e-01	0.0632
84164	ASCC2	LZE22D1	Human	Esophagus	HGIN	1.34e-06	2.98e-01	0.0595
84164	ASCC2	LZE22T	Human	Esophagus	ESCC	3.76e-08	4.52e-01	0.068
84164	ASCC2	LZE24T	Human	Esophagus	ESCC	2.52e-24	6.31e-01	0.0596
84164	ASCC2	LZE21T	Human	Esophagus	ESCC	5.18e-10	6.12e-01	0.0655
84164	ASCC2	P1T-E	Human	Esophagus	ESCC	2.93e-17	6.61e-01	0.0875
84164	ASCC2	P2T-E	Human	Esophagus	ESCC	9.65e-32	3.95e-01	0.1177
84164	ASCC2	P4T-E	Human	Esophagus	ESCC	3.10e-26	6.29e-01	0.1323
84164	ASCC2	P5T-E	Human	Esophagus	ESCC	3.64e-17	1.63e-01	0.1327
84164	ASCC2	P8T-E	Human	Esophagus	ESCC	1.15e-37	6.61e-01	0.0889
84164	ASCC2	P9T-E	Human	Esophagus	ESCC	1.31e-13	3.11e-01	0.1131
84164	ASCC2	P10T-E	Human	Esophagus	ESCC	2.51e-43	6.96e-01	0.116
84164	ASCC2	P11T-E	Human	Esophagus	ESCC	1.96e-15	6.95e-01	0.1426
84164	ASCC2	P12T-E	Human	Esophagus	ESCC	2.79e-22	4.34e-01	0.1122
84164	ASCC2	P15T-E	Human	Esophagus	ESCC	8.44e-33	6.75e-01	0.1149
84164	ASCC2	P16T-E	Human	Esophagus	ESCC	8.08e-26	5.05e-01	0.1153

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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:000641727	Esophagus	HGIN	regulation of translation	139/2587	468/18723	1.46e-19	7.98e-17	139
GO:001049826	Esophagus	HGIN	proteasomal protein catabolic process	139/2587	490/18723	1.20e-17	3.41e-15	139
GO:004316126	Esophagus	HGIN	proteasome-mediated ubiquitin-dependent protein catabolic process	114/2587	412/18723	7.00e-14	1.20e-11	114
GO:000641418	Esophagus	HGIN	translational elongation	22/2587	55/18723	1.46e-06	5.56e-05	22
GO:0010498111	Esophagus	ESCC	proteasomal protein catabolic process	369/8552	490/18723	1.13e-41	1.80e-38	369
GO:0043161111	Esophagus	ESCC	proteasome-mediated ubiquitin-dependent protein catabolic process	312/8552	412/18723	3.53e-36	4.48e-33	312
GO:0006417111	Esophagus	ESCC	regulation of translation	304/8552	468/18723	1.53e-17	1.33e-15	304
GO:000641419	Esophagus	ESCC	translational elongation	41/8552	55/18723	1.26e-05	1.16e-04	41
GO:00431617	Liver	NAFLD	proteasome-mediated ubiquitin-dependent protein catabolic process	91/1882	412/18723	3.00e-13	1.75e-10	91
GO:00104987	Liver	NAFLD	proteasomal protein catabolic process	101/1882	490/18723	1.35e-12	6.09e-10	101
GO:00064177	Liver	NAFLD	regulation of translation	85/1882	468/18723	4.58e-08	4.54e-06	85
GO:00064145	Liver	NAFLD	translational elongation	16/1882	55/18723	6.71e-05	1.44e-03	16
GO:001049812	Liver	Cirrhotic	proteasomal protein catabolic process	216/4634	490/18723	2.52e-21	9.29e-19	216
GO:004316112	Liver	Cirrhotic	proteasome-mediated ubiquitin-dependent protein catabolic process	184/4634	412/18723	4.52e-19	8.85e-17	184
GO:000641712	Liver	Cirrhotic	regulation of translation	194/4634	468/18723	7.28e-16	8.79e-14	194
GO:001049822	Liver	HCC	proteasomal protein catabolic process	351/7958	490/18723	6.92e-40	1.46e-36	351
GO:004316122	Liver	HCC	proteasome-mediated ubiquitin-dependent protein catabolic process	299/7958	412/18723	7.82e-36	8.27e-33	299
GO:000641722	Liver	HCC	regulation of translation	287/7958	468/18723	8.79e-17	8.08e-15	287
GO:000641412	Liver	HCC	translational elongation	36/7958	55/18723	4.94e-04	3.23e-03	36
GO:001049820	Oral cavity	OSCC	proteasomal protein catabolic process	336/7305	490/18723	5.45e-41	8.63e-38	336

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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

ASCC2

SNV

Missense_Mutation

c.1859N>G

p.Tyr620Cys

p.Y620C

Q9H1I8

protein_coding

deleterious(0)

possibly_damaging(0.85)

TCGA-A8-A06Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

ASCC2

SNV

Missense_Mutation

novel

c.919G>T

p.Asp307Tyr

p.D307Y

Q9H1I8

protein_coding

tolerated(0.06)

probably_damaging(0.979)

TCGA-A8-A08F-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

ASCC2

SNV

Missense_Mutation

rs770062271

c.209N>C

p.Leu70Pro

p.L70P

Q9H1I8

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-D8-A1JK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ASCC2

SNV

Missense_Mutation

rs770062271

c.209T>C

p.Leu70Pro

p.L70P

Q9H1I8

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-D8-A1XK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicine+cyclophosphamide

ASCC2

SNV

Missense_Mutation

c.647N>A

p.Gly216Glu

p.G216E

Q9H1I8

protein_coding

tolerated(1)

benign(0.018)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

ASCC2

SNV

Missense_Mutation

c.658N>C

p.Asn220His

p.N220H

Q9H1I8

protein_coding

deleterious(0.02)

benign(0.155)

TCGA-D8-A1XS-01

Breast

breast invasive carcinoma

Male

<65

III/IV

Chemotherapy

adriamycin+cyclophosphamide

ASCC2

SNV

Missense_Mutation

novel

c.1405N>T

p.Asp469Tyr

p.D469Y

Q9H1I8

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-E2-A2P6-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

ASCC2

insertion

Nonsense_Mutation

novel

c.1221_1222insCGTCAGTAAACTTGTTGGAAAAGGACCTTGGATTAGTAGGAAG

p.Arg409GlnfsTer2

p.R409Qfs*2

Q9H1I8

protein_coding

TCGA-A2-A0CQ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

ASCC2

insertion

In_Frame_Ins

novel

c.920_921insTTTTCC

p.Asp307_Leu308insPhePro

p.D307_L308insFP

Q9H1I8

protein_coding

TCGA-A8-A08F-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

5-fluorouracil

ASCC2

insertion

Nonsense_Mutation

novel

c.1562_1563insGAGCCGGGTGCACAAGGGCAAGAGGTGAGTG

p.Asp522SerfsTer9

p.D522Sfs*9

Q9H1I8

protein_coding

TCGA-AO-A0J5-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate

zoledronic

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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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