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: AHCY

Gene summary for AHCY

Gene summary.

Gene information	Species	Human
	Gene symbol	AHCY
	Gene ID	191
	Gene name	adenosylhomocysteinase
	Gene Alias	SAHH
	Cytomap	20q11.22
	Gene Type	protein-coding
	GO ID	GO:0001666
	UniProtAcc	P23526

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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
191	AHCY	Dong_P3	Human	Prostate	Tumor	5.08e-14	1.88e-01	0.0278
191	AHCY	Dong_P4	Human	Prostate	Tumor	1.38e-08	2.93e-01	0.0292
191	AHCY	Dong_P5	Human	Prostate	Tumor	6.74e-28	1.31e-01	0.053
191	AHCY	GSM5353215_PA_AUG_PB_1B_S2	Human	Prostate	Tumor	2.39e-02	2.98e-01	0.1557
191	AHCY	GSM5353221_PA_PB2A_Pool_1_3_S25_L001	Human	Prostate	Tumor	1.55e-04	3.83e-01	0.1633
191	AHCY	GSM5353222_PA_PB2B_Pool_1_3_S52_L002	Human	Prostate	Tumor	3.32e-05	3.81e-01	0.1608
191	AHCY	GSM5353223_PA_PB2B_Pool_2_S26_L001	Human	Prostate	Tumor	3.06e-04	4.56e-01	0.1604
191	AHCY	GSM5353227_PA_PR5199-193K_Pool_1_2_3_S55_L002	Human	Prostate	Tumor	3.05e-06	3.28e-01	0.1602
191	AHCY	GSM5353228_PA_PR5199-640K_Pool_1_3_S108_L004	Human	Prostate	Tumor	2.52e-02	2.89e-01	0.1537
191	AHCY	GSM5353232_PA_PR5249_T1_S3_L001	Human	Prostate	Tumor	5.68e-03	2.28e-01	0.1439
191	AHCY	GSM5353236_PA_PR5251_T1_S7_L001	Human	Prostate	Tumor	6.42e-03	4.31e-01	0.1608
191	AHCY	GSM5353237_PA_PR5251_T2_S8_L001	Human	Prostate	Tumor	1.44e-03	6.03e-01	0.1622
191	AHCY	GSM5353240_PA_PR5254_T1_S15_L001	Human	Prostate	Tumor	1.01e-08	4.01e-01	0.1575
191	AHCY	GSM5353243_PA_PR5261_T1_S23_L002	Human	Prostate	Tumor	2.74e-13	2.57e-01	0.1545
191	AHCY	GSM5353244_PA_PR5261_T2_S24_L002	Human	Prostate	Tumor	2.32e-12	1.79e-01	0.1569
191	AHCY	P4_S8_cSCC	Human	Skin	cSCC	6.15e-12	1.69e-01	-0.3095
191	AHCY	P5_S10_cSCC	Human	Skin	cSCC	1.80e-02	4.72e-02	-0.299
191	AHCY	P1_cSCC	Human	Skin	cSCC	1.00e-41	1.41e+00	0.0292
191	AHCY	P2_cSCC	Human	Skin	cSCC	4.99e-33	8.46e-01	-0.024
191	AHCY	P4_cSCC	Human	Skin	cSCC	6.89e-34	9.25e-01	-0.00290000000000005

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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
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:1903311	Colorectum	AD	regulation of mRNA metabolic process	117/3918	288/18723	1.69e-14	4.23e-12	117
GO:0072521	Colorectum	AD	purine-containing compound metabolic process	153/3918	416/18723	4.34e-14	1.01e-11	153
GO:0050684	Colorectum	AD	regulation of mRNA processing	61/3918	137/18723	4.23e-10	3.58e-08	61
GO:0044270	Colorectum	AD	cellular nitrogen compound catabolic process	147/3918	451/18723	3.35e-09	2.23e-07	147
GO:0046700	Colorectum	AD	heterocycle catabolic process	145/3918	445/18723	4.37e-09	2.84e-07	145
GO:0034655	Colorectum	AD	nucleobase-containing compound catabolic process	133/3918	407/18723	1.56e-08	9.12e-07	133
GO:0019439	Colorectum	AD	aromatic compound catabolic process	146/3918	467/18723	7.48e-08	3.84e-06	146
GO:1901361	Colorectum	AD	organic cyclic compound catabolic process	153/3918	495/18723	8.23e-08	4.18e-06	153
GO:0006913	Colorectum	AD	nucleocytoplasmic transport	102/3918	301/18723	1.00e-07	4.85e-06	102
GO:0051169	Colorectum	AD	nuclear transport	102/3918	301/18723	1.00e-07	4.85e-06	102
GO:1901653	Colorectum	AD	cellular response to peptide	114/3918	359/18723	8.32e-07	2.88e-05	114
GO:0044282	Colorectum	AD	small molecule catabolic process	118/3918	376/18723	1.05e-06	3.55e-05	118
GO:0071375	Colorectum	AD	cellular response to peptide hormone stimulus	95/3918	290/18723	1.50e-06	4.66e-05	95
GO:0043434	Colorectum	AD	response to peptide hormone	126/3918	414/18723	2.70e-06	7.86e-05	126
GO:0007623	Colorectum	AD	circadian rhythm	72/3918	210/18723	4.50e-06	1.21e-04	72
GO:0048511	Colorectum	AD	rhythmic process	94/3918	298/18723	1.00e-05	2.34e-04	94
GO:0031667	Colorectum	AD	response to nutrient levels	138/3918	474/18723	1.22e-05	2.68e-04	138
GO:0002028	Colorectum	AD	regulation of sodium ion transport	36/3918	90/18723	2.89e-05	5.37e-04	36
GO:0006790	Colorectum	AD	sulfur compound metabolic process	101/3918	339/18723	6.46e-05	1.07e-03	101
GO:0051168	Colorectum	AD	nuclear export	53/3918	154/18723	6.89e-05	1.11e-03	53

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa00270	Liver	Cirrhotic	Cysteine and methionine metabolism	27/2530	52/8465	6.98e-04	4.15e-03	2.56e-03	27
hsa002701	Liver	Cirrhotic	Cysteine and methionine metabolism	27/2530	52/8465	6.98e-04	4.15e-03	2.56e-03	27
hsa002702	Liver	HCC	Cysteine and methionine metabolism	35/4020	52/8465	3.03e-03	9.94e-03	5.53e-03	35
hsa002703	Liver	HCC	Cysteine and methionine metabolism	35/4020	52/8465	3.03e-03	9.94e-03	5.53e-03	35

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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

AHCY

SNV

Missense_Mutation

rs377090568

c.1280N>T

p.Pro427Leu

p.P427L

P23526

protein_coding

tolerated_low_confidence(0.06)

benign(0.118)

TCGA-AR-A24L-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

AHCY

SNV

Missense_Mutation

novel

c.243C>G

p.Ile81Met

p.I81M

P23526

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.979)

TCGA-AR-A2LE-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

AHCY

SNV

Missense_Mutation

novel

c.635N>A

p.Ala212Asp

p.A212D

P23526

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.973)

TCGA-BH-A18Q-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

AHCY

SNV

Missense_Mutation

c.322N>C

p.Glu108Gln

p.E108Q

P23526

protein_coding

deleterious_low_confidence(0.02)

possibly_damaging(0.876)

TCGA-C8-A134-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

5-fluorouracil

AHCY

insertion

Frame_Shift_Ins

novel

c.220-1_220insCCCAGCGACCCCACAGGAAAGAGCTGCTTTGTCCCAT

p.Val74ProfsTer54

p.V74Pfs*54

P23526

protein_coding

TCGA-AN-A0FN-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

AHCY

SNV

Missense_Mutation

rs767274069

c.1027N>T

p.Arg343Trp

p.R343W

P23526

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.966)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

AHCY

SNV

Missense_Mutation

novel

c.501G>A

p.Met167Ile

p.M167I

P23526

protein_coding

deleterious_low_confidence(0)

benign(0.115)

TCGA-VS-A959-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

AHCY

SNV

Missense_Mutation

novel

c.802G>C

p.Glu268Gln

p.E268Q

P23526

protein_coding

tolerated_low_confidence(0.24)

benign(0.056)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

AHCY

SNV

Missense_Mutation

c.722N>C

p.Ile241Thr

p.I241T

P23526

protein_coding

deleterious_low_confidence(0)

possibly_damaging(0.871)

TCGA-AA-3966-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

AHCY

SNV

Missense_Mutation

c.1094A>G

p.Gln365Arg

p.Q365R

P23526

protein_coding

deleterious_low_confidence(0.01)

possibly_damaging(0.829)

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
191	AHCY	DRUGGABLE GENOME, G PROTEIN COUPLED RECEPTOR, ENZYME	inhibitor	178101808	CHEMBL202701

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