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: HNRNPA3

Gene summary for HNRNPA3

Gene summary.

Gene information	Species	Human
	Gene symbol	HNRNPA3
	Gene ID	220988
	Gene name	heterogeneous nuclear ribonucleoprotein A3
	Gene Alias	2610510D13Rik
	Cytomap	2q31.2
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	B4DDB6

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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
220988	HNRNPA3	GSM4909277	Human	Breast	Precancer	3.33e-03	1.53e-01	0.0177
220988	HNRNPA3	GSM4909281	Human	Breast	IDC	1.92e-22	5.34e-01	0.21
220988	HNRNPA3	GSM4909282	Human	Breast	IDC	6.68e-11	3.42e-01	-0.0288
220988	HNRNPA3	GSM4909285	Human	Breast	IDC	1.13e-24	5.24e-01	0.21
220988	HNRNPA3	GSM4909287	Human	Breast	IDC	1.90e-16	3.83e-01	0.2057
220988	HNRNPA3	GSM4909288	Human	Breast	IDC	7.18e-10	2.26e-01	0.0988
220988	HNRNPA3	GSM4909294	Human	Breast	IDC	2.76e-03	-2.28e-02	0.2022
220988	HNRNPA3	GSM4909296	Human	Breast	IDC	3.49e-14	-4.23e-01	0.1524
220988	HNRNPA3	GSM4909297	Human	Breast	IDC	3.53e-19	-2.15e-01	0.1517
220988	HNRNPA3	GSM4909302	Human	Breast	IDC	2.48e-07	-3.80e-01	0.1545
220988	HNRNPA3	GSM4909309	Human	Breast	IDC	5.56e-05	-2.64e-01	0.0483
220988	HNRNPA3	GSM4909311	Human	Breast	IDC	1.27e-42	-4.60e-01	0.1534
220988	HNRNPA3	GSM4909312	Human	Breast	IDC	2.33e-14	-2.72e-01	0.1552
220988	HNRNPA3	GSM4909313	Human	Breast	IDC	1.73e-03	-1.93e-01	0.0391
220988	HNRNPA3	GSM4909316	Human	Breast	IDC	3.04e-06	1.76e-01	0.21
220988	HNRNPA3	GSM4909318	Human	Breast	IDC	8.83e-10	4.50e-01	0.2031
220988	HNRNPA3	GSM4909319	Human	Breast	IDC	2.63e-45	-6.09e-01	0.1563
220988	HNRNPA3	GSM4909320	Human	Breast	IDC	2.42e-15	-6.92e-01	0.1575
220988	HNRNPA3	GSM4909321	Human	Breast	IDC	3.71e-17	-2.18e-01	0.1559
220988	HNRNPA3	brca2	Human	Breast	Precancer	2.09e-13	3.66e-01	-0.024

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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
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid 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:00083809	Breast	Precancer	RNA splicing	65/1080	434/18723	1.27e-12	2.53e-10	65
GO:00003759	Breast	Precancer	RNA splicing, via transesterification reactions	52/1080	324/18723	1.74e-11	2.22e-09	52
GO:00003779	Breast	Precancer	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	51/1080	320/18723	3.55e-11	4.04e-09	51
GO:00003989	Breast	Precancer	mRNA splicing, via spliceosome	51/1080	320/18723	3.55e-11	4.04e-09	51
GO:00064039	Breast	Precancer	RNA localization	23/1080	201/18723	1.34e-03	1.41e-02	23
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:000640313	Breast	IDC	RNA localization	27/1434	201/18723	3.04e-03	2.60e-02	27
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:000640322	Breast	DCIS	RNA localization	27/1390	201/18723	1.97e-03	1.84e-02	27
GO:00512368	Cervix	CC	establishment of RNA localization	39/2311	166/18723	4.76e-05	7.25e-04	39
GO:00506578	Cervix	CC	nucleic acid transport	38/2311	163/18723	7.06e-05	9.85e-04	38
GO:00506588	Cervix	CC	RNA transport	38/2311	163/18723	7.06e-05	9.85e-04	38
GO:000640310	Cervix	CC	RNA localization	43/2311	201/18723	2.00e-04	2.29e-03	43
GO:00510284	Cervix	CC	mRNA transport	31/2311	130/18723	2.05e-04	2.33e-03	31

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0501416	Breast	Precancer	Amyotrophic lateral sclerosis	98/684	364/8465	2.13e-28	8.41e-27	6.44e-27	98
hsa030408	Breast	Precancer	Spliceosome	39/684	217/8465	1.44e-06	2.27e-05	1.74e-05	39
hsa0501417	Breast	Precancer	Amyotrophic lateral sclerosis	98/684	364/8465	2.13e-28	8.41e-27	6.44e-27	98
hsa0304013	Breast	Precancer	Spliceosome	39/684	217/8465	1.44e-06	2.27e-05	1.74e-05	39
hsa0501423	Breast	IDC	Amyotrophic lateral sclerosis	102/867	364/8465	1.29e-22	5.22e-21	3.91e-21	102
hsa0304023	Breast	IDC	Spliceosome	40/867	217/8465	1.53e-04	1.42e-03	1.06e-03	40
hsa0501433	Breast	IDC	Amyotrophic lateral sclerosis	102/867	364/8465	1.29e-22	5.22e-21	3.91e-21	102
hsa0304033	Breast	IDC	Spliceosome	40/867	217/8465	1.53e-04	1.42e-03	1.06e-03	40
hsa0501443	Breast	DCIS	Amyotrophic lateral sclerosis	101/846	364/8465	7.14e-23	2.88e-21	2.12e-21	101
hsa0304043	Breast	DCIS	Spliceosome	40/846	217/8465	8.97e-05	8.52e-04	6.28e-04	40
hsa0501453	Breast	DCIS	Amyotrophic lateral sclerosis	101/846	364/8465	7.14e-23	2.88e-21	2.12e-21	101
hsa0304053	Breast	DCIS	Spliceosome	40/846	217/8465	8.97e-05	8.52e-04	6.28e-04	40
hsa0501418	Cervix	CC	Amyotrophic lateral sclerosis	103/1267	364/8465	1.79e-11	4.47e-10	2.64e-10	103
hsa0501419	Cervix	CC	Amyotrophic lateral sclerosis	103/1267	364/8465	1.79e-11	4.47e-10	2.64e-10	103
hsa05014	Colorectum	AD	Amyotrophic lateral sclerosis	164/2092	364/8465	4.28e-18	1.27e-16	8.09e-17	164
hsa03040	Colorectum	AD	Spliceosome	73/2092	217/8465	1.73e-03	9.68e-03	6.18e-03	73
hsa050141	Colorectum	AD	Amyotrophic lateral sclerosis	164/2092	364/8465	4.28e-18	1.27e-16	8.09e-17	164
hsa030401	Colorectum	AD	Spliceosome	73/2092	217/8465	1.73e-03	9.68e-03	6.18e-03	73
hsa050142	Colorectum	SER	Amyotrophic lateral sclerosis	138/1580	364/8465	9.89e-19	2.99e-17	2.17e-17	138
hsa050143	Colorectum	SER	Amyotrophic lateral sclerosis	138/1580	364/8465	9.89e-19	2.99e-17	2.17e-17	138

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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

HNRNPA3

SNV

Missense_Mutation

novel

c.1125N>G

p.Ser375Arg

p.S375R

P51991

protein_coding

tolerated_low_confidence(0.29)

benign(0.094)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

HNRNPA3

SNV

Missense_Mutation

novel

c.1132N>G

p.Phe378Val

p.F378V

P51991

protein_coding

deleterious_low_confidence(0)

benign(0.055)

TCGA-AR-A255-01

Breast

breast invasive carcinoma

Female

<65

I/II

Targeted Molecular therapy

trastuzumab

HNRNPA3

SNV

Missense_Mutation

c.307N>T

p.Arg103Cys

p.R103C

P51991

protein_coding

deleterious(0.04)

benign(0.067)

TCGA-D8-A1XQ-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HNRNPA3

insertion

Frame_Shift_Ins

novel

c.1120_1121insATTATTATTACTATTATTATGAGATGGA

p.Gly374AspfsTer11

p.G374Dfs*11

P51991

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

HNRNPA3

insertion

In_Frame_Ins

novel

c.1122_1123insCTTGCTGTGTCACTC

p.Gly374_Ser375insLeuAlaValSerLeu

p.G374_S375insLAVSL

P51991

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

HNRNPA3

SNV

Missense_Mutation

novel

c.835N>A

p.Gly279Ser

p.G279S

P51991

protein_coding

tolerated(0.22)

possibly_damaging(0.604)

TCGA-A6-6780-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

HNRNPA3

SNV

Missense_Mutation

rs768895205

c.958N>A

p.Gly320Ser

p.G320S

P51991

protein_coding

tolerated(0.3)

benign(0.011)

TCGA-AA-3672-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

HNRNPA3

SNV

Missense_Mutation

c.558N>T

p.Gln186His

p.Q186H

P51991

protein_coding

deleterious(0.01)

probably_damaging(0.949)

TCGA-AG-A002-01

Colorectum

rectum adenocarcinoma

Male

<65

I/II

Unknown

HNRNPA3

deletion

Frame_Shift_Del

c.62delN

p.Glu23ArgfsTer12

p.E23Rfs*12

P51991

protein_coding

TCGA-A6-5665-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

HNRNPA3

insertion

Frame_Shift_Ins

novel

c.798_799insT

p.Tyr267LeufsTer2

p.Y267Lfs*2

P51991

protein_coding

TCGA-CA-5797-01

Colorectum

colon adenocarcinoma

Male

<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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