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: AKR1C2

Gene summary for AKR1C2

Gene summary.

Gene information	Species	Human
	Gene symbol	AKR1C2
	Gene ID	1646
	Gene name	aldo-keto reductase family 1 member C2
	Gene Alias	AKR1C-pseudo
	Cytomap	10p15.1
	Gene Type	protein-coding
	GO ID	GO:0006066
	UniProtAcc	P52895

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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
1646	AKR1C2	Tumor	Human	Cervix	CC	1.69e-10	5.27e-01	0.1241
1646	AKR1C2	sample3	Human	Cervix	CC	1.01e-18	4.37e-01	0.1387
1646	AKR1C2	T3	Human	Cervix	CC	2.98e-11	4.21e-01	0.1389
1646	AKR1C2	LZE2T	Human	Esophagus	ESCC	1.12e-15	3.07e+00	0.082
1646	AKR1C2	LZE4T	Human	Esophagus	ESCC	9.70e-58	3.67e+00	0.0811
1646	AKR1C2	LZE7T	Human	Esophagus	ESCC	1.71e-34	3.34e+00	0.0667
1646	AKR1C2	LZE20T	Human	Esophagus	ESCC	7.85e-14	1.07e+00	0.0662
1646	AKR1C2	LZE21D1	Human	Esophagus	HGIN	1.56e-06	1.89e+00	0.0632
1646	AKR1C2	LZE22D1	Human	Esophagus	HGIN	1.48e-06	1.15e+00	0.0595
1646	AKR1C2	LZE22T	Human	Esophagus	ESCC	1.64e-15	2.54e+00	0.068
1646	AKR1C2	LZE24T	Human	Esophagus	ESCC	5.37e-53	3.34e+00	0.0596
1646	AKR1C2	LZE21T	Human	Esophagus	ESCC	1.01e-28	3.08e+00	0.0655
1646	AKR1C2	P4T-E	Human	Esophagus	ESCC	7.09e-67	3.86e+00	0.1323
1646	AKR1C2	P8T-E	Human	Esophagus	ESCC	6.52e-09	6.76e-01	0.0889
1646	AKR1C2	P9T-E	Human	Esophagus	ESCC	4.35e-80	3.91e+00	0.1131
1646	AKR1C2	P12T-E	Human	Esophagus	ESCC	3.27e-68	3.37e+00	0.1122
1646	AKR1C2	P15T-E	Human	Esophagus	ESCC	5.14e-87	4.18e+00	0.1149
1646	AKR1C2	P20T-E	Human	Esophagus	ESCC	1.31e-25	1.60e+00	0.1124
1646	AKR1C2	P21T-E	Human	Esophagus	ESCC	9.38e-38	1.61e+00	0.1617
1646	AKR1C2	P22T-E	Human	Esophagus	ESCC	1.38e-96	2.90e+00	0.1236

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
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

∗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:190165410	Cervix	CC	response to ketone	45/2311	194/18723	1.83e-05	3.44e-04	45
GO:00518964	Cervix	CC	regulation of protein kinase B signaling	39/2311	185/18723	5.25e-04	5.10e-03	39
GO:00518973	Cervix	CC	positive regulation of protein kinase B signaling	28/2311	120/18723	5.90e-04	5.59e-03	28
GO:00434913	Cervix	CC	protein kinase B signaling	43/2311	211/18723	5.95e-04	5.60e-03	43
GO:00973059	Cervix	CC	response to alcohol	46/2311	253/18723	4.40e-03	2.69e-02	46
GO:190165420	Esophagus	HGIN	response to ketone	48/2587	194/18723	3.17e-05	8.12e-04	48
GO:00066929	Esophagus	HGIN	prostanoid metabolic process	17/2587	49/18723	1.84e-04	3.48e-03	17
GO:00066939	Esophagus	HGIN	prostaglandin metabolic process	17/2587	49/18723	1.84e-04	3.48e-03	17
GO:009730520	Esophagus	HGIN	response to alcohol	54/2587	253/18723	6.46e-04	8.87e-03	54
GO:00306386	Esophagus	HGIN	polyketide metabolic process	6/2587	10/18723	8.81e-04	1.13e-02	6
GO:00306476	Esophagus	HGIN	aminoglycoside antibiotic metabolic process	6/2587	10/18723	8.81e-04	1.13e-02	6
GO:00445986	Esophagus	HGIN	doxorubicin metabolic process	6/2587	10/18723	8.81e-04	1.13e-02	6
GO:19016614	Esophagus	HGIN	quinone metabolic process	13/2587	40/18723	2.04e-03	2.13e-02	13
GO:190166112	Esophagus	ESCC	quinone metabolic process	34/8552	40/18723	3.00e-07	4.27e-06	34
GO:00060668	Esophagus	ESCC	alcohol metabolic process	202/8552	353/18723	7.32e-06	7.26e-05	202
GO:1901654111	Esophagus	ESCC	response to ketone	118/8552	194/18723	1.45e-05	1.31e-04	118
GO:00066318	Esophagus	ESCC	fatty acid metabolic process	217/8552	390/18723	4.21e-05	3.39e-04	217
GO:19016574	Esophagus	ESCC	glycosyl compound metabolic process	57/8552	88/18723	2.32e-04	1.44e-03	57
GO:00421805	Esophagus	ESCC	cellular ketone metabolic process	120/8552	211/18723	6.70e-04	3.55e-03	120
GO:19016556	Esophagus	ESCC	cellular response to ketone	59/8552	96/18723	1.32e-03	6.30e-03	59

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0520839	Esophagus	HGIN	Chemical carcinogenesis - reactive oxygen species	92/1383	223/8465	2.41e-19	9.83e-18	7.80e-18	92
hsa05208115	Esophagus	HGIN	Chemical carcinogenesis - reactive oxygen species	92/1383	223/8465	2.41e-19	9.83e-18	7.80e-18	92
hsa05208211	Esophagus	ESCC	Chemical carcinogenesis - reactive oxygen species	168/4205	223/8465	1.83e-15	6.81e-14	3.49e-14	168
hsa05208310	Esophagus	ESCC	Chemical carcinogenesis - reactive oxygen species	168/4205	223/8465	1.83e-15	6.81e-14	3.49e-14	168
hsa0520842	Liver	HCC	Chemical carcinogenesis - reactive oxygen species	167/4020	223/8465	2.85e-17	1.91e-15	1.06e-15	167
hsa0520852	Liver	HCC	Chemical carcinogenesis - reactive oxygen species	167/4020	223/8465	2.85e-17	1.91e-15	1.06e-15	167
hsa0520830	Oral cavity	OSCC	Chemical carcinogenesis - reactive oxygen species	150/3704	223/8465	6.45e-13	1.20e-11	6.11e-12	150
hsa05208114	Oral cavity	OSCC	Chemical carcinogenesis - reactive oxygen species	150/3704	223/8465	6.45e-13	1.20e-11	6.11e-12	150
hsa05208210	Oral cavity	LP	Chemical carcinogenesis - reactive oxygen species	119/2418	223/8465	3.00e-15	8.32e-14	5.37e-14	119
hsa0520838	Oral cavity	LP	Chemical carcinogenesis - reactive oxygen species	119/2418	223/8465	3.00e-15	8.32e-14	5.37e-14	119

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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

AKR1C2

SNV

Missense_Mutation

rs782255440

c.139C>T

p.His47Tyr

p.H47Y

P52895

protein_coding

deleterious(0.02)

benign(0.001)

TCGA-5L-AAT1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Hormone Therapy

letrozol

AKR1C2

SNV

Missense_Mutation

c.580C>G

p.His194Asp

p.H194D

P52895

protein_coding

deleterious(0)

probably_damaging(0.994)

TCGA-A2-A0YK-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

AKR1C2

SNV

Missense_Mutation

c.362N>T

p.Ser121Phe

p.S121F

P52895

protein_coding

tolerated(0.06)

possibly_damaging(0.597)

TCGA-D8-A1XA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

AKR1C2

SNV

Missense_Mutation

c.504N>G

p.Phe168Leu

p.F168L

P52895

protein_coding

deleterious(0.01)

probably_damaging(0.999)

TCGA-C5-A7UE-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AKR1C2

SNV

Missense_Mutation

rs781814762

c.197N>A

p.Arg66Gln

p.R66Q

P52895

protein_coding

tolerated(0.15)

benign(0.055)

TCGA-A5-A2K5-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

AKR1C2

SNV

Missense_Mutation

rs782385243

c.749N>A

p.Arg250Gln

p.R250Q

P52895

protein_coding

tolerated(0.23)

benign(0.044)

TCGA-AX-A063-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

AKR1C2

SNV

Missense_Mutation

novel

c.55C>A

p.Leu19Met

p.L19M

P52895

protein_coding

deleterious(0.02)

probably_damaging(0.921)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

AKR1C2

SNV

Missense_Mutation

c.394N>T

p.Asp132Tyr

p.D132Y

P52895

protein_coding

deleterious(0.01)

probably_damaging(0.965)

TCGA-B5-A0JY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

doxorubicin

AKR1C2

SNV

Missense_Mutation

novel

c.627N>C

p.Lys209Asn

p.K209N

P52895

protein_coding

tolerated(0.14)

benign(0.062)

TCGA-B5-A1MR-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

AKR1C2

SNV

Missense_Mutation

novel

c.325N>A

p.Asp109Asn

p.D109N

P52895

protein_coding

tolerated(0.07)

benign(0.358)

TCGA-B5-A3FA-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
1646	AKR1C2	DRUGGABLE GENOME, ENZYME		URSODEOXYCHOLIC ACID

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