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: HNRNPA2B1

Gene summary for HNRNPA2B1

Gene summary.

Gene information	Species	Human
	Gene symbol	HNRNPA2B1
	Gene ID	3181
	Gene name	heterogeneous nuclear ribonucleoprotein A2/B1
	Gene Alias	HNRNPA2
	Cytomap	7p15.2
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	P22626

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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
3181	HNRNPA2B1	GSM4909277	Human	Breast	Precancer	2.33e-04	3.33e-01	0.0177
3181	HNRNPA2B1	GSM4909282	Human	Breast	IDC	6.84e-03	2.30e-01	-0.0288
3181	HNRNPA2B1	GSM4909285	Human	Breast	IDC	1.78e-06	3.00e-01	0.21
3181	HNRNPA2B1	GSM4909286	Human	Breast	IDC	2.36e-29	-4.86e-01	0.1081
3181	HNRNPA2B1	GSM4909288	Human	Breast	IDC	3.28e-02	-2.26e-01	0.0988
3181	HNRNPA2B1	GSM4909291	Human	Breast	IDC	1.45e-02	-3.63e-01	0.1753
3181	HNRNPA2B1	GSM4909293	Human	Breast	IDC	2.41e-05	-1.29e-01	0.1581
3181	HNRNPA2B1	GSM4909294	Human	Breast	IDC	9.93e-08	-8.88e-02	0.2022
3181	HNRNPA2B1	GSM4909296	Human	Breast	IDC	2.36e-10	-3.50e-01	0.1524
3181	HNRNPA2B1	GSM4909297	Human	Breast	IDC	2.51e-20	-1.95e-01	0.1517
3181	HNRNPA2B1	GSM4909301	Human	Breast	IDC	3.61e-07	-3.62e-01	0.1577
3181	HNRNPA2B1	GSM4909302	Human	Breast	IDC	3.04e-02	-2.95e-01	0.1545
3181	HNRNPA2B1	GSM4909309	Human	Breast	IDC	9.60e-05	-3.52e-01	0.0483
3181	HNRNPA2B1	GSM4909311	Human	Breast	IDC	3.65e-65	-8.93e-01	0.1534
3181	HNRNPA2B1	GSM4909312	Human	Breast	IDC	6.00e-15	-4.43e-01	0.1552
3181	HNRNPA2B1	GSM4909313	Human	Breast	IDC	4.57e-06	-3.95e-01	0.0391
3181	HNRNPA2B1	GSM4909315	Human	Breast	IDC	9.26e-03	-2.50e-01	0.21
3181	HNRNPA2B1	GSM4909316	Human	Breast	IDC	5.15e-04	-2.19e-01	0.21
3181	HNRNPA2B1	GSM4909319	Human	Breast	IDC	1.79e-60	-5.68e-01	0.1563
3181	HNRNPA2B1	GSM4909320	Human	Breast	IDC	4.19e-14	-7.10e-01	0.1575

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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
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
GC		CAG: Chronic atrophic gastritis
		CAG with IM: Chronic atrophic gastritis with intestinal metaplasia
		CSG: Chronic superficial gastritis
		GC: Gastric cancer
		SIM: Severe intestinal metaplasia
		WIM: Wild intestinal metaplasia
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:00709188	Esophagus	ESCC	production of small RNA involved in gene silencing by RNA	38/8552	54/18723	2.08e-04	1.31e-03	38
GO:003105311	Esophagus	ESCC	primary miRNA processing	11/8552	13/18723	4.76e-03	1.85e-02	11
GO:00083807	Liver	NAFLD	RNA splicing	70/1882	434/18723	4.62e-05	1.10e-03	70
GO:00069137	Liver	NAFLD	nucleocytoplasmic transport	51/1882	301/18723	1.39e-04	2.62e-03	51
GO:00511697	Liver	NAFLD	nuclear transport	51/1882	301/18723	1.39e-04	2.62e-03	51
GO:00351964	Liver	NAFLD	production of miRNAs involved in gene silencing by miRNA	14/1882	52/18723	4.58e-04	6.71e-03	14
GO:00330444	Liver	NAFLD	regulation of chromosome organization	34/1882	187/18723	4.69e-04	6.74e-03	34
GO:00510526	Liver	NAFLD	regulation of DNA metabolic process	56/1882	359/18723	5.95e-04	7.92e-03	56
GO:00003777	Liver	NAFLD	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	51/1882	320/18723	6.21e-04	8.18e-03	51
GO:00003987	Liver	NAFLD	mRNA splicing, via spliceosome	51/1882	320/18723	6.21e-04	8.18e-03	51
GO:00310504	Liver	NAFLD	dsRNA processing	14/1882	54/18723	6.94e-04	8.88e-03	14
GO:00709184	Liver	NAFLD	production of small RNA involved in gene silencing by RNA	14/1882	54/18723	6.94e-04	8.88e-03	14
GO:00003757	Liver	NAFLD	RNA splicing, via transesterification reactions	51/1882	324/18723	8.28e-04	1.02e-02	51
GO:00511687	Liver	NAFLD	nuclear export	28/1882	154/18723	1.42e-03	1.58e-02	28
GO:00323922	Liver	NAFLD	DNA geometric change	18/1882	90/18723	3.34e-03	2.93e-02	18
GO:00344704	Liver	NAFLD	ncRNA processing	57/1882	395/18723	3.34e-03	2.93e-02	57
GO:00512366	Liver	NAFLD	establishment of RNA localization	28/1882	166/18723	4.35e-03	3.57e-02	28
GO:00064037	Liver	NAFLD	RNA localization	32/1882	201/18723	5.96e-03	4.48e-02	32
GO:00108337	Liver	NAFLD	telomere maintenance via telomere lengthening	16/1882	81/18723	6.20e-03	4.62e-02	16
GO:19043566	Liver	NAFLD	regulation of telomere maintenance via telomere lengthening	13/1882	61/18723	6.77e-03	4.79e-02	13

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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
hsa0501417	Breast	Precancer	Amyotrophic lateral sclerosis	98/684	364/8465	2.13e-28	8.41e-27	6.44e-27	98
hsa0501423	Breast	IDC	Amyotrophic lateral sclerosis	102/867	364/8465	1.29e-22	5.22e-21	3.91e-21	102
hsa0501433	Breast	IDC	Amyotrophic lateral sclerosis	102/867	364/8465	1.29e-22	5.22e-21	3.91e-21	102
hsa0501443	Breast	DCIS	Amyotrophic lateral sclerosis	101/846	364/8465	7.14e-23	2.88e-21	2.12e-21	101
hsa0501453	Breast	DCIS	Amyotrophic lateral sclerosis	101/846	364/8465	7.14e-23	2.88e-21	2.12e-21	101
hsa05014	Colorectum	AD	Amyotrophic lateral sclerosis	164/2092	364/8465	4.28e-18	1.27e-16	8.09e-17	164
hsa050141	Colorectum	AD	Amyotrophic lateral sclerosis	164/2092	364/8465	4.28e-18	1.27e-16	8.09e-17	164
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
hsa050144	Colorectum	MSS	Amyotrophic lateral sclerosis	156/1875	364/8465	1.43e-19	4.62e-18	2.83e-18	156
hsa050145	Colorectum	MSS	Amyotrophic lateral sclerosis	156/1875	364/8465	1.43e-19	4.62e-18	2.83e-18	156
hsa050146	Colorectum	MSI-H	Amyotrophic lateral sclerosis	95/797	364/8465	2.31e-21	1.50e-19	1.26e-19	95
hsa050147	Colorectum	MSI-H	Amyotrophic lateral sclerosis	95/797	364/8465	2.31e-21	1.50e-19	1.26e-19	95
hsa050148	Colorectum	FAP	Amyotrophic lateral sclerosis	91/1404	364/8465	1.84e-05	2.36e-04	1.44e-04	91
hsa050149	Colorectum	FAP	Amyotrophic lateral sclerosis	91/1404	364/8465	1.84e-05	2.36e-04	1.44e-04	91
hsa0501420	Endometrium	AEH	Amyotrophic lateral sclerosis	123/1197	364/8465	2.17e-22	7.82e-21	5.72e-21	123
hsa05014110	Endometrium	AEH	Amyotrophic lateral sclerosis	123/1197	364/8465	2.17e-22	7.82e-21	5.72e-21	123
hsa0501425	Endometrium	EEC	Amyotrophic lateral sclerosis	128/1237	364/8465	9.83e-24	4.04e-22	3.01e-22	128
hsa0501435	Endometrium	EEC	Amyotrophic lateral sclerosis	128/1237	364/8465	9.83e-24	4.04e-22	3.01e-22	128

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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

HNRNPA2B1

SNV

Missense_Mutation

c.951N>C

p.Lys317Asn

p.K317N

P22626

protein_coding

deleterious(0.03)

benign(0.264)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HNRNPA2B1

SNV

Missense_Mutation

c.209N>T

p.Ser70Leu

p.S70L

P22626

protein_coding

deleterious(0.03)

probably_damaging(0.975)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HNRNPA2B1

SNV

Missense_Mutation

c.124G>C

p.Glu42Gln

p.E42Q

P22626

protein_coding

tolerated(0.13)

benign(0.192)

TCGA-BH-A0HP-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Chemotherapy

doxorubicin

HNRNPA2B1

SNV

Missense_Mutation

c.46N>A

p.Glu16Lys

p.E16K

P22626

protein_coding

deleterious(0.01)

probably_damaging(0.932)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

HNRNPA2B1

SNV

Missense_Mutation

novel

c.869A>G

p.Tyr290Cys

p.Y290C

P22626

protein_coding

tolerated(0.17)

benign(0.339)

TCGA-OL-A5RW-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

HNRNPA2B1

SNV

Missense_Mutation

novel

c.353G>A

p.Gly118Glu

p.G118E

P22626

protein_coding

deleterious(0.01)

probably_damaging(0.954)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

HNRNPA2B1

insertion

In_Frame_Ins

novel

c.356_357insGAACAAAAA

p.Ile119delinsMetAsnLysAsn

p.I119delinsMNKN

P22626

protein_coding

TCGA-DS-A1OC-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

gemcitabine

HNRNPA2B1

SNV

Missense_Mutation

c.185N>T

p.Arg62Ile

p.R62I

P22626

protein_coding

deleterious(0.01)

probably_damaging(0.975)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

HNRNPA2B1

SNV

Missense_Mutation

c.565N>C

p.Ser189Pro

p.S189P

P22626

protein_coding

tolerated(0.08)

probably_damaging(0.927)

TCGA-G4-6628-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Unknown

HNRNPA2B1

SNV

Missense_Mutation

novel

c.389A>C

p.Asp130Ala

p.D130A

P22626

protein_coding

deleterious(0)

possibly_damaging(0.467)

TCGA-A5-A0G1-01

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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