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: HSD11B1

Gene summary for HSD11B1

Gene summary.

Gene information	Species	Human
	Gene symbol	HSD11B1
	Gene ID	3290
	Gene name	hydroxysteroid 11-beta dehydrogenase 1
	Gene Alias	11-DH
	Cytomap	1q32.2
	Gene Type	protein-coding
	GO ID	GO:0006629
	UniProtAcc	P28845

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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
3290	HSD11B1	NAFLD1	Human	Liver	NAFLD	5.59e-09	6.42e-01	-0.04
3290	HSD11B1	S41	Human	Liver	Cirrhotic	1.85e-02	4.25e-01	-0.0343
3290	HSD11B1	S43	Human	Liver	Cirrhotic	2.05e-04	-6.15e-03	-0.0187
3290	HSD11B1	S44	Human	Liver	HCC	4.03e-03	7.79e-01	-0.0083
3290	HSD11B1	HCC1_Meng	Human	Liver	HCC	1.07e-06	-2.00e-01	0.0246
3290	HSD11B1	HCC2_Meng	Human	Liver	HCC	1.12e-04	-1.99e-01	0.0107
3290	HSD11B1	Pt13.a	Human	Liver	HCC	2.58e-03	-1.86e-01	0.021
3290	HSD11B1	Pt14.d	Human	Liver	HCC	1.67e-02	-1.84e-01	0.0143

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗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:19013616	Liver	NAFLD	organic cyclic compound catabolic process	105/1882	495/18723	7.04e-14	5.15e-11	105
GO:00082023	Liver	NAFLD	steroid metabolic process	69/1882	319/18723	5.90e-10	1.28e-07	69
GO:00160426	Liver	NAFLD	lipid catabolic process	63/1882	320/18723	1.35e-07	1.02e-05	63
GO:190136111	Liver	Cirrhotic	organic cyclic compound catabolic process	213/4634	495/18723	1.58e-19	3.67e-17	213
GO:000820211	Liver	Cirrhotic	steroid metabolic process	143/4634	319/18723	2.79e-15	3.18e-13	143
GO:001604212	Liver	Cirrhotic	lipid catabolic process	112/4634	320/18723	2.31e-05	3.03e-04	112
GO:00303242	Liver	Cirrhotic	lung development	65/4634	177/18723	2.49e-04	2.25e-03	65
GO:00303232	Liver	Cirrhotic	respiratory tube development	66/4634	181/18723	2.82e-04	2.49e-03	66
GO:00605411	Liver	Cirrhotic	respiratory system development	67/4634	203/18723	4.81e-03	2.52e-02	67
GO:190136121	Liver	HCC	organic cyclic compound catabolic process	325/7958	495/18723	6.52e-26	2.18e-23	325
GO:00082022	Liver	HCC	steroid metabolic process	188/7958	319/18723	1.96e-09	5.63e-08	188
GO:001604221	Liver	HCC	lipid catabolic process	175/7958	320/18723	6.50e-06	7.88e-05	175
GO:003032311	Liver	HCC	respiratory tube development	95/7958	181/18723	4.15e-03	1.81e-02	95
GO:003032411	Liver	HCC	lung development	91/7958	177/18723	1.01e-02	3.80e-02	91

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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

HSD11B1

SNV

Missense_Mutation

c.134N>T

p.Gly45Val

p.G45V

P28845

protein_coding

deleterious(0)

probably_damaging(0.992)

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

HSD11B1

SNV

Missense_Mutation

novel

c.570N>T

p.Leu190Phe

p.L190F

P28845

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-AO-A0JD-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

HSD11B1

SNV

Missense_Mutation

c.374C>G

p.Ser125Cys

p.S125C

P28845

protein_coding

tolerated(0.18)

possibly_damaging(0.627)

TCGA-BH-A0B0-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

HSD11B1

SNV

Missense_Mutation

novel

c.107N>G

p.Lys36Arg

p.K36R

P28845

protein_coding

tolerated(1)

benign(0.001)

TCGA-BH-A5IZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

HSD11B1

SNV

Missense_Mutation

novel

c.383T>C

p.Leu128Pro

p.L128P

P28845

protein_coding

tolerated(0.28)

benign(0)

TCGA-LL-A73Y-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Chemotherapy

taxotere

HSD11B1

insertion

Nonsense_Mutation

novel

c.572_573insGTGAGAATTAACCAGTCTGGTGAACATTTTTT

p.Asp191GlufsTer2

p.D191Efs*2

P28845

protein_coding

TCGA-AO-A0JD-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

cyclophosphamide

HSD11B1

deletion

Frame_Shift_Del

novel

c.252delC

p.Ser85GlnfsTer12

p.S85Qfs*12

P28845

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

HSD11B1

deletion

Frame_Shift_Del

novel

c.204delA

p.Glu69LysfsTer28

p.E69Kfs*28

P28845

protein_coding

TCGA-EW-A2FV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

HSD11B1

SNV

Missense_Mutation

novel

c.34C>A

p.Leu12Met

p.L12M

P28845

protein_coding

deleterious(0.03)

possibly_damaging(0.62)

TCGA-MY-A913-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

HSD11B1

SNV

Missense_Mutation

rs200402963

c.295N>A

p.Ala99Thr

p.A99T

P28845

protein_coding

tolerated(0.14)

possibly_damaging(0.659)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

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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
3290	HSD11B1	DRUGGABLE GENOME, ENZYME, SHORT CHAIN DEHYDROGENASE REDUCTASE	inhibitor	381118868	BMS-823778
3290	HSD11B1	DRUGGABLE GENOME, ENZYME, SHORT CHAIN DEHYDROGENASE REDUCTASE		Flavanone	FLAVANONE
3290	HSD11B1	DRUGGABLE GENOME, ENZYME, SHORT CHAIN DEHYDROGENASE REDUCTASE		BVT.2733
3290	HSD11B1	DRUGGABLE GENOME, ENZYME, SHORT CHAIN DEHYDROGENASE REDUCTASE		BMS-816336
3290	HSD11B1	DRUGGABLE GENOME, ENZYME, SHORT CHAIN DEHYDROGENASE REDUCTASE		HPP-851
3290	HSD11B1	DRUGGABLE GENOME, ENZYME, SHORT CHAIN DEHYDROGENASE REDUCTASE	inhibitor	178103929	ABT-384
3290	HSD11B1	DRUGGABLE GENOME, ENZYME, SHORT CHAIN DEHYDROGENASE REDUCTASE		JTT-654
3290	HSD11B1	DRUGGABLE GENOME, ENZYME, SHORT CHAIN DEHYDROGENASE REDUCTASE	inhibitor	223366028	AZD-4017
3290	HSD11B1	DRUGGABLE GENOME, ENZYME, SHORT CHAIN DEHYDROGENASE REDUCTASE		INCB13739
3290	HSD11B1	DRUGGABLE GENOME, ENZYME, SHORT CHAIN DEHYDROGENASE REDUCTASE		GLYCYRRHIZIN	GLYCYRRHIZIN

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