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: GRINA

Gene summary for GRINA

Gene summary.

Gene information	Species	Human
	Gene symbol	GRINA
	Gene ID	2907
	Gene name	glutamate ionotropic receptor NMDA type subunit associated protein 1
	Gene Alias	HNRGW
	Cytomap	8q24.3
	Gene Type	protein-coding
	GO ID	GO:0006873
	UniProtAcc	Q7Z429

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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
2907	GRINA	GSM4909281	Human	Breast	IDC	6.26e-05	3.37e-01	0.21
2907	GRINA	GSM4909287	Human	Breast	IDC	2.87e-02	2.12e-01	0.2057
2907	GRINA	GSM4909293	Human	Breast	IDC	1.52e-06	3.37e-01	0.1581
2907	GRINA	GSM4909296	Human	Breast	IDC	6.02e-04	8.15e-02	0.1524
2907	GRINA	GSM4909297	Human	Breast	IDC	2.50e-03	3.73e-02	0.1517
2907	GRINA	GSM4909298	Human	Breast	IDC	2.83e-15	4.80e-01	0.1551
2907	GRINA	GSM4909304	Human	Breast	IDC	5.89e-27	6.37e-01	0.1636
2907	GRINA	GSM4909305	Human	Breast	IDC	1.90e-02	2.30e-01	0.0436
2907	GRINA	GSM4909306	Human	Breast	IDC	2.64e-10	4.65e-01	0.1564
2907	GRINA	GSM4909308	Human	Breast	IDC	2.57e-06	2.59e-01	0.158
2907	GRINA	GSM4909309	Human	Breast	IDC	4.77e-03	2.09e-01	0.0483
2907	GRINA	GSM4909311	Human	Breast	IDC	1.15e-28	3.42e-01	0.1534
2907	GRINA	GSM4909312	Human	Breast	IDC	1.85e-12	3.79e-01	0.1552
2907	GRINA	GSM4909317	Human	Breast	IDC	5.12e-17	4.59e-01	0.1355
2907	GRINA	GSM4909319	Human	Breast	IDC	2.17e-31	2.72e-01	0.1563
2907	GRINA	GSM4909320	Human	Breast	IDC	4.35e-03	2.50e-01	0.1575
2907	GRINA	GSM4909321	Human	Breast	IDC	5.16e-15	2.73e-01	0.1559
2907	GRINA	M1	Human	Breast	IDC	8.19e-07	3.10e-01	0.1577
2907	GRINA	P1	Human	Breast	IDC	3.92e-03	-4.64e-03	0.1527
2907	GRINA	DCIS2	Human	Breast	DCIS	1.05e-38	8.37e-02	0.0085

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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
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
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:0097193111	Esophagus	ESCC	intrinsic apoptotic signaling pathway	222/8552	288/18723	5.87e-28	2.02e-25	222
GO:2001233111	Esophagus	ESCC	regulation of apoptotic signaling pathway	256/8552	356/18723	4.11e-24	1.04e-21	256
GO:0034976111	Esophagus	ESCC	response to endoplasmic reticulum stress	192/8552	256/18723	7.15e-22	1.30e-19	192
GO:2001242111	Esophagus	ESCC	regulation of intrinsic apoptotic signaling pathway	128/8552	164/18723	1.75e-17	1.50e-15	128
GO:2001234111	Esophagus	ESCC	negative regulation of apoptotic signaling pathway	161/8552	224/18723	1.24e-15	8.09e-14	161
GO:2001243111	Esophagus	ESCC	negative regulation of intrinsic apoptotic signaling pathway	78/8552	98/18723	5.50e-12	2.10e-10	78
GO:1905897111	Esophagus	ESCC	regulation of response to endoplasmic reticulum stress	63/8552	82/18723	8.16e-09	1.66e-07	63
GO:0070059111	Esophagus	ESCC	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	50/8552	63/18723	4.37e-08	7.96e-07	50
GO:1903573111	Esophagus	ESCC	negative regulation of response to endoplasmic reticulum stress	34/8552	44/18723	1.90e-05	1.67e-04	34
GO:0032469110	Esophagus	ESCC	endoplasmic reticulum calcium ion homeostasis	21/8552	25/18723	9.12e-05	6.54e-04	21
GO:190223516	Esophagus	ESCC	regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	24/8552	32/18723	7.22e-04	3.77e-03	24
GO:1902236111	Esophagus	ESCC	negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	16/8552	20/18723	1.85e-03	8.40e-03	16
GO:00349767	Liver	Cirrhotic	response to endoplasmic reticulum stress	130/4634	256/18723	1.72e-19	3.86e-17	130
GO:200123312	Liver	Cirrhotic	regulation of apoptotic signaling pathway	163/4634	356/18723	2.62e-18	4.43e-16	163
GO:009719312	Liver	Cirrhotic	intrinsic apoptotic signaling pathway	130/4634	288/18723	2.69e-14	2.45e-12	130
GO:20012427	Liver	Cirrhotic	regulation of intrinsic apoptotic signaling pathway	82/4634	164/18723	2.35e-12	1.71e-10	82
GO:20012347	Liver	Cirrhotic	negative regulation of apoptotic signaling pathway	102/4634	224/18723	8.40e-12	5.60e-10	102
GO:19058977	Liver	Cirrhotic	regulation of response to endoplasmic reticulum stress	46/4634	82/18723	1.28e-09	5.56e-08	46
GO:20012437	Liver	Cirrhotic	negative regulation of intrinsic apoptotic signaling pathway	47/4634	98/18723	5.26e-07	1.17e-05	47
GO:19035737	Liver	Cirrhotic	negative regulation of response to endoplasmic reticulum stress	26/4634	44/18723	1.30e-06	2.59e-05	26

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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

GRINA

SNV

Missense_Mutation

c.658T>G

p.Phe220Val

p.F220V

Q7Z429

protein_coding

tolerated(0.29)

benign(0.031)

TCGA-E9-A1ND-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

aromasin

GRINA

insertion

Frame_Shift_Ins

novel

c.17_18insT

p.Leu8PhefsTer119

p.L8Ffs*119

Q7Z429

protein_coding

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

GRINA

SNV

Missense_Mutation

rs560551768

c.73C>G

p.Pro25Ala

p.P25A

Q7Z429

protein_coding

deleterious(0.05)

benign(0.098)

TCGA-AZ-4313-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

GRINA

SNV

Missense_Mutation

c.302A>G

p.Gln101Arg

p.Q101R

Q7Z429

protein_coding

tolerated(0.26)

possibly_damaging(0.901)

TCGA-NH-A5IV-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

GRINA

SNV

Missense_Mutation

rs782307051

c.487N>T

p.Arg163Cys

p.R163C

Q7Z429

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AX-A06F-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

GRINA

SNV

Missense_Mutation

rs200050797

c.560N>T

p.Ala187Val

p.A187V

Q7Z429

protein_coding

tolerated(0.06)

benign(0.327)

TCGA-AX-A1C9-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

GRINA

SNV

Missense_Mutation

rs560551768

c.73C>G

p.Pro25Ala

p.P25A

Q7Z429

protein_coding

deleterious(0.05)

benign(0.098)

TCGA-B5-A0JU-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

GRINA

SNV

Missense_Mutation

novel

c.488G>A

p.Arg163His

p.R163H

Q7Z429

protein_coding

deleterious(0)

probably_damaging(0.995)

TCGA-EO-A22U-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

GRINA

SNV

Missense_Mutation

rs560551768

c.73C>G

p.Pro25Ala

p.P25A

Q7Z429

protein_coding

deleterious(0.05)

benign(0.098)

TCGA-EO-A3KX-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

GRINA

SNV

Missense_Mutation

novel

c.15N>T

p.Lys5Asn

p.K5N

Q7Z429

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.505)

TCGA-EY-A1GI-01

Endometrium

uterine corpus endometrioid carcinoma

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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