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: HNRNPL

Gene summary for HNRNPL

Gene summary.

Gene information	Species	Human
	Gene symbol	HNRNPL
	Gene ID	3191
	Gene name	heterogeneous nuclear ribonucleoprotein L
	Gene Alias	HNRPL
	Cytomap	19q13.2
	Gene Type	protein-coding
	GO ID	GO:0000375
	UniProtAcc	P14866

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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
3191	HNRNPL	HTA11_3410_2000001011	Human	Colorectum	AD	2.67e-05	1.21e-01	0.0155
3191	HNRNPL	HTA11_1938_2000001011	Human	Colorectum	AD	2.48e-05	6.22e-01	-0.0811
3191	HNRNPL	HTA11_347_2000001011	Human	Colorectum	AD	2.52e-09	5.07e-01	-0.1954
3191	HNRNPL	HTA11_696_2000001011	Human	Colorectum	AD	3.21e-04	3.67e-01	-0.1464
3191	HNRNPL	HTA11_866_2000001011	Human	Colorectum	AD	2.41e-02	3.04e-01	-0.1001
3191	HNRNPL	HTA11_1391_2000001011	Human	Colorectum	AD	2.89e-05	5.12e-01	-0.059
3191	HNRNPL	HTA11_866_3004761011	Human	Colorectum	AD	5.08e-14	7.36e-01	0.096
3191	HNRNPL	HTA11_7663_2000001011	Human	Colorectum	SER	2.73e-04	7.05e-01	0.0131
3191	HNRNPL	HTA11_10623_2000001011	Human	Colorectum	AD	4.99e-03	4.78e-01	-0.0177
3191	HNRNPL	HTA11_7696_3000711011	Human	Colorectum	AD	1.83e-22	8.20e-01	0.0674
3191	HNRNPL	HTA11_6818_2000001021	Human	Colorectum	AD	1.48e-08	6.18e-01	0.0588
3191	HNRNPL	HTA11_99999970781_79442	Human	Colorectum	MSS	1.28e-14	6.11e-01	0.294
3191	HNRNPL	HTA11_99999965062_69753	Human	Colorectum	MSI-H	1.03e-07	1.31e+00	0.3487
3191	HNRNPL	HTA11_99999965104_69814	Human	Colorectum	MSS	1.24e-05	5.70e-01	0.281
3191	HNRNPL	HTA11_99999971662_82457	Human	Colorectum	MSS	6.74e-11	5.98e-01	0.3859
3191	HNRNPL	A015-C-203	Human	Colorectum	FAP	8.00e-06	-2.86e-02	-0.1294
3191	HNRNPL	A001-C-108	Human	Colorectum	FAP	3.99e-02	-9.42e-02	-0.0272
3191	HNRNPL	A002-C-205	Human	Colorectum	FAP	1.56e-05	-1.84e-01	-0.1236
3191	HNRNPL	A015-C-006	Human	Colorectum	FAP	9.32e-04	-7.52e-02	-0.0994
3191	HNRNPL	A002-C-114	Human	Colorectum	FAP	5.29e-06	-2.32e-01	-0.1561

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
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
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:000838017	Endometrium	EEC	RNA splicing	111/2168	434/18723	2.45e-16	1.13e-13	111
GO:004348417	Endometrium	EEC	regulation of RNA splicing	55/2168	148/18723	5.21e-16	1.95e-13	55
GO:000037516	Endometrium	EEC	RNA splicing, via transesterification reactions	88/2168	324/18723	7.46e-15	2.63e-12	88
GO:000037716	Endometrium	EEC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	87/2168	320/18723	9.97e-15	3.15e-12	87
GO:000039816	Endometrium	EEC	mRNA splicing, via spliceosome	87/2168	320/18723	9.97e-15	3.15e-12	87
GO:190331115	Endometrium	EEC	regulation of mRNA metabolic process	79/2168	288/18723	1.01e-13	2.64e-11	79
GO:004802417	Endometrium	EEC	regulation of mRNA splicing, via spliceosome	40/2168	101/18723	4.45e-13	9.86e-11	40
GO:005068414	Endometrium	EEC	regulation of mRNA processing	43/2168	137/18723	4.52e-10	4.59e-08	43
GO:000038014	Endometrium	EEC	alternative mRNA splicing, via spliceosome	26/2168	77/18723	2.42e-07	1.05e-05	26
GO:000038114	Endometrium	EEC	regulation of alternative mRNA splicing, via spliceosome	20/2168	60/18723	7.27e-06	1.67e-04	20
GO:000838026	Esophagus	HGIN	RNA splicing	160/2587	434/18723	3.74e-34	1.12e-30	160
GO:000037520	Esophagus	HGIN	RNA splicing, via transesterification reactions	115/2587	324/18723	3.16e-23	3.80e-20	115
GO:000037720	Esophagus	HGIN	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	113/2587	320/18723	1.24e-22	9.26e-20	113
GO:000039820	Esophagus	HGIN	mRNA splicing, via spliceosome	113/2587	320/18723	1.24e-22	9.26e-20	113
GO:004348427	Esophagus	HGIN	regulation of RNA splicing	59/2587	148/18723	3.61e-15	7.22e-13	59
GO:190331120	Esophagus	HGIN	regulation of mRNA metabolic process	91/2587	288/18723	5.06e-15	9.78e-13	91
GO:005068419	Esophagus	HGIN	regulation of mRNA processing	55/2587	137/18723	2.17e-14	3.94e-12	55
GO:004802426	Esophagus	HGIN	regulation of mRNA splicing, via spliceosome	42/2587	101/18723	6.35e-12	7.78e-10	42
GO:000038018	Esophagus	HGIN	alternative mRNA splicing, via spliceosome	32/2587	77/18723	2.06e-09	1.54e-07	32
GO:000038118	Esophagus	HGIN	regulation of alternative mRNA splicing, via spliceosome	22/2587	60/18723	7.92e-06	2.40e-04	22

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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

HNRNPL

SNV

Missense_Mutation

c.1540N>A

p.Glu514Lys

p.E514K

P14866

protein_coding

deleterious(0.03)

benign(0.033)

TCGA-A2-A0EY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

HNRNPL

SNV

Missense_Mutation

novel

c.502N>A

p.Pro168Thr

p.P168T

P14866

protein_coding

deleterious(0.04)

probably_damaging(0.999)

TCGA-A7-A3RF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

HNRNPL

SNV

Missense_Mutation

c.1391N>T

p.Ser464Leu

p.S464L

P14866

protein_coding

tolerated(0.51)

benign(0.059)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HNRNPL

SNV

Missense_Mutation

novel

c.1560N>G

p.Ile520Met

p.I520M

P14866

protein_coding

tolerated(0.23)

benign(0.001)

TCGA-AC-A3W5-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

docetaxel

HNRNPL

insertion

Frame_Shift_Ins

novel

c.850_851insCCTTAGAAACCAGCAGTGGCTCCTTTGAGAGTCTGGTGAGGGT

p.Asp284AlafsTer26

p.D284Afs*26

P14866

protein_coding

TCGA-A2-A0CP-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

HNRNPL

insertion

Frame_Shift_Ins

novel

c.1284_1285insAG

p.Gly429ArgfsTer5

p.G429Rfs*5

P14866

protein_coding

TCGA-AN-A04C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HNRNPL

insertion

In_Frame_Ins

novel

c.1283_1284insGGGCCCAATTTCACAAGAACCGCATTGGCG

p.Asp428delinsGluGlyProIleSerGlnGluProHisTrpArg

p.D428delinsEGPISQEPHWR

P14866

protein_coding

TCGA-AN-A04C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

HNRNPL

SNV

Missense_Mutation

c.1021N>A

p.Glu341Lys

p.E341K

P14866

protein_coding

tolerated(0.56)

benign(0.018)

TCGA-C5-A1MI-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HNRNPL

SNV

Missense_Mutation

c.719N>T

p.Ser240Leu

p.S240L

P14866

protein_coding

tolerated(0.09)

benign(0.057)

TCGA-MY-A5BD-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HNRNPL

SNV

Missense_Mutation

c.796N>A

p.Glu266Lys

p.E266K

P14866

protein_coding

deleterious(0.02)

benign(0.017)

TCGA-AA-3715-01

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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