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: LRRC8C

Gene summary for LRRC8C

Gene summary.

Gene information	Species	Human
	Gene symbol	LRRC8C
	Gene ID	84230
	Gene name	leucine rich repeat containing 8 VRAC subunit C
	Gene Alias	AD158
	Cytomap	1p22.2
	Gene Type	protein-coding
	GO ID	GO:0001408
	UniProtAcc	Q8TDW0

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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
84230	LRRC8C	C04	Human	Oral cavity	OSCC	9.00e-09	4.69e-01	0.2633
84230	LRRC8C	C21	Human	Oral cavity	OSCC	1.12e-12	5.41e-01	0.2678
84230	LRRC8C	C30	Human	Oral cavity	OSCC	5.09e-11	6.28e-01	0.3055
84230	LRRC8C	C06	Human	Oral cavity	OSCC	4.05e-02	5.81e-01	0.2699
84230	LRRC8C	EOLP-1	Human	Oral cavity	EOLP	1.47e-04	2.03e-01	-0.0202
84230	LRRC8C	NEOLP-2	Human	Oral cavity	NEOLP	1.04e-03	1.53e-01	-0.0196
84230	LRRC8C	NEOLP-3	Human	Oral cavity	NEOLP	5.02e-05	1.51e-01	-0.0191
84230	LRRC8C	SYSMH3	Human	Oral cavity	OSCC	5.88e-04	1.18e-01	0.2442

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma

∗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:001593114	Oral cavity	OSCC	nucleobase-containing compound transport	150/7305	222/18723	4.86e-18	5.04e-16	150
GO:006219720	Oral cavity	OSCC	cellular response to chemical stress	204/7305	337/18723	6.89e-16	5.19e-14	204
GO:007121416	Oral cavity	OSCC	cellular response to abiotic stimulus	186/7305	331/18723	1.38e-10	4.10e-09	186
GO:010400416	Oral cavity	OSCC	cellular response to environmental stimulus	186/7305	331/18723	1.38e-10	4.10e-09	186
GO:00069706	Oral cavity	OSCC	response to osmotic stress	50/7305	84/18723	1.11e-04	8.15e-04	50
GO:0051259	Oral cavity	OSCC	protein complex oligomerization	121/7305	238/18723	1.29e-04	9.21e-04	121
GO:00714706	Oral cavity	OSCC	cellular response to osmotic stress	26/7305	41/18723	1.34e-03	6.62e-03	26
GO:19012642	Oral cavity	OSCC	carbohydrate derivative transport	44/7305	80/18723	2.67e-03	1.16e-02	44
GO:001593121	Oral cavity	EOLP	nucleobase-containing compound transport	58/2218	222/18723	3.44e-09	2.10e-07	58
GO:006219726	Oral cavity	EOLP	cellular response to chemical stress	64/2218	337/18723	8.49e-05	1.01e-03	64
GO:1901679	Oral cavity	EOLP	nucleotide transmembrane transport	8/2218	20/18723	1.29e-03	9.17e-03	8
GO:00157483	Oral cavity	EOLP	organophosphate ester transport	28/2218	140/18723	3.66e-03	2.05e-02	28
GO:0006862	Oral cavity	EOLP	nucleotide transport	10/2218	37/18723	9.12e-03	4.15e-02	10
GO:006219733	Oral cavity	NEOLP	cellular response to chemical stress	75/2005	337/18723	4.87e-10	3.97e-08	75
GO:001593131	Oral cavity	NEOLP	nucleobase-containing compound transport	48/2005	222/18723	1.51e-06	3.77e-05	48
GO:007121424	Oral cavity	NEOLP	cellular response to abiotic stimulus	55/2005	331/18723	6.38e-04	5.43e-03	55
GO:010400424	Oral cavity	NEOLP	cellular response to environmental stimulus	55/2005	331/18723	6.38e-04	5.43e-03	55
GO:19016791	Oral cavity	NEOLP	nucleotide transmembrane transport	7/2005	20/18723	3.51e-03	2.06e-02	7
GO:001574811	Oral cavity	NEOLP	organophosphate ester transport	25/2005	140/18723	7.16e-03	3.63e-02	25
GO:007147014	Oral cavity	NEOLP	cellular response to osmotic stress	10/2005	41/18723	9.71e-03	4.55e-02	10

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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

LRRC8C

SNV

Missense_Mutation

c.304G>C

p.Asp102His

p.D102H

Q8TDW0

protein_coding

tolerated(0.08)

possibly_damaging(0.873)

TCGA-A2-A0D2-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

LRRC8C

SNV

Missense_Mutation

novel

c.1444C>T

p.His482Tyr

p.H482Y

Q8TDW0

protein_coding

deleterious(0)

benign(0.424)

TCGA-A2-A3XT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

LRRC8C

SNV

Missense_Mutation

rs751573376

c.10N>A

p.Val4Met

p.V4M

Q8TDW0

protein_coding

deleterious(0.01)

possibly_damaging(0.529)

TCGA-A7-A13D-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

LRRC8C

SNV

Missense_Mutation

novel

c.529N>C

p.Glu177Gln

p.E177Q

Q8TDW0

protein_coding

deleterious(0)

benign(0.213)

TCGA-A8-A079-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

5-fluorouracil

LRRC8C

SNV

Missense_Mutation

novel

c.1292T>C

p.Ile431Thr

p.I431T

Q8TDW0

protein_coding

deleterious(0.02)

benign(0.017)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

LRRC8C

SNV

Missense_Mutation

novel

c.173N>C

p.Arg58Thr

p.R58T

Q8TDW0

protein_coding

tolerated(0.34)

benign(0.005)

TCGA-BH-A2L8-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

LRRC8C

SNV

Missense_Mutation

c.293G>A

p.Gly98Asp

p.G98D

Q8TDW0

protein_coding

deleterious(0.01)

probably_damaging(1)

TCGA-D8-A1JK-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

LRRC8C

SNV

Missense_Mutation

c.2237C>A

p.Pro746Gln

p.P746Q

Q8TDW0

protein_coding

deleterious(0.02)

possibly_damaging(0.734)

TCGA-D8-A27M-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

methotrexate+5

LRRC8C

SNV

Missense_Mutation

rs200185887

c.1492G>A

p.Val498Ile

p.V498I

Q8TDW0

protein_coding

tolerated(0.34)

benign(0.211)

TCGA-E9-A1R6-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

LRRC8C

SNV

Missense_Mutation

c.2407N>C

p.Glu803Gln

p.E803Q

Q8TDW0

protein_coding

tolerated(0.05)

probably_damaging(0.947)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

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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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