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	P52T-E	Human	Esophagus	ESCC	8.38e-44	2.17e+00	0.1555
2907	GRINA	P54T-E	Human	Esophagus	ESCC	1.34e-41	1.55e+00	0.0975
2907	GRINA	P56T-E	Human	Esophagus	ESCC	6.05e-19	3.30e+00	0.1613
2907	GRINA	P57T-E	Human	Esophagus	ESCC	6.43e-37	1.35e+00	0.0926
2907	GRINA	P61T-E	Human	Esophagus	ESCC	9.31e-18	9.91e-01	0.099
2907	GRINA	P62T-E	Human	Esophagus	ESCC	1.52e-108	2.66e+00	0.1302
2907	GRINA	P65T-E	Human	Esophagus	ESCC	2.25e-46	1.38e+00	0.0978
2907	GRINA	P74T-E	Human	Esophagus	ESCC	3.06e-60	2.29e+00	0.1479
2907	GRINA	P75T-E	Human	Esophagus	ESCC	2.79e-89	2.89e+00	0.1125
2907	GRINA	P76T-E	Human	Esophagus	ESCC	2.38e-66	1.67e+00	0.1207
2907	GRINA	P79T-E	Human	Esophagus	ESCC	1.84e-77	2.05e+00	0.1154
2907	GRINA	P80T-E	Human	Esophagus	ESCC	5.12e-55	2.51e+00	0.155
2907	GRINA	P82T-E	Human	Esophagus	ESCC	8.53e-26	2.20e+00	0.1072
2907	GRINA	P83T-E	Human	Esophagus	ESCC	1.28e-76	3.65e+00	0.1738
2907	GRINA	P84T-E	Human	Esophagus	ESCC	1.51e-14	1.76e+00	0.0933
2907	GRINA	P89T-E	Human	Esophagus	ESCC	1.20e-34	3.37e+00	0.1752
2907	GRINA	P91T-E	Human	Esophagus	ESCC	1.94e-22	3.01e+00	0.1828
2907	GRINA	P107T-E	Human	Esophagus	ESCC	2.42e-71	2.72e+00	0.171
2907	GRINA	P126T-E	Human	Esophagus	ESCC	4.79e-10	1.77e+00	0.1125
2907	GRINA	P127T-E	Human	Esophagus	ESCC	3.47e-14	4.42e-01	0.0826

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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:200123314	Breast	IDC	regulation of apoptotic signaling pathway	82/1434	356/18723	6.27e-20	5.93e-17	82
GO:009719314	Breast	IDC	intrinsic apoptotic signaling pathway	69/1434	288/18723	6.32e-18	2.99e-15	69
GO:200124214	Breast	IDC	regulation of intrinsic apoptotic signaling pathway	47/1434	164/18723	8.25e-16	2.93e-13	47
GO:200123414	Breast	IDC	negative regulation of apoptotic signaling pathway	49/1434	224/18723	1.45e-11	2.58e-09	49
GO:200124314	Breast	IDC	negative regulation of intrinsic apoptotic signaling pathway	27/1434	98/18723	2.91e-09	2.50e-07	27
GO:003497614	Breast	IDC	response to endoplasmic reticulum stress	43/1434	256/18723	8.42e-07	3.82e-05	43
GO:190589714	Breast	IDC	regulation of response to endoplasmic reticulum stress	19/1434	82/18723	1.04e-05	2.87e-04	19
GO:190357313	Breast	IDC	negative regulation of response to endoplasmic reticulum stress	13/1434	44/18723	1.62e-05	4.05e-04	13
GO:007005914	Breast	IDC	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress	14/1434	63/18723	2.37e-04	3.75e-03	14
GO:003246913	Breast	IDC	endoplasmic reticulum calcium ion homeostasis	8/1434	25/18723	3.85e-04	5.40e-03	8
GO:190223614	Breast	IDC	negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	7/1434	20/18723	4.85e-04	6.42e-03	7
GO:19022355	Breast	IDC	regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	8/1434	32/18723	2.32e-03	2.10e-02	8
GO:200123324	Breast	DCIS	regulation of apoptotic signaling pathway	81/1390	356/18723	3.51e-20	3.31e-17	81
GO:009719324	Breast	DCIS	intrinsic apoptotic signaling pathway	68/1390	288/18723	4.93e-18	2.33e-15	68
GO:200124224	Breast	DCIS	regulation of intrinsic apoptotic signaling pathway	47/1390	164/18723	2.49e-16	9.38e-14	47
GO:200123424	Breast	DCIS	negative regulation of apoptotic signaling pathway	48/1390	224/18723	1.70e-11	3.22e-09	48
GO:200124322	Breast	DCIS	negative regulation of intrinsic apoptotic signaling pathway	27/1390	98/18723	1.48e-09	1.42e-07	27
GO:003497622	Breast	DCIS	response to endoplasmic reticulum stress	43/1390	256/18723	3.65e-07	1.71e-05	43
GO:190589722	Breast	DCIS	regulation of response to endoplasmic reticulum stress	19/1390	82/18723	6.65e-06	1.86e-04	19
GO:190357322	Breast	DCIS	negative regulation of response to endoplasmic reticulum stress	13/1390	44/18723	1.16e-05	2.98e-04	13

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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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