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: MAN1A2

Gene summary for MAN1A2

Gene summary.

Gene information	Species	Human
	Gene symbol	MAN1A2
	Gene ID	10905
	Gene name	mannosidase alpha class 1A member 2
	Gene Alias	MAN1B
	Cytomap	1p12
	Gene Type	protein-coding
	GO ID	GO:0005975
	UniProtAcc	O60476

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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
10905	MAN1A2	CA_HPV_1	Human	Cervix	CC	1.12e-02	-1.07e-01	0.0264
10905	MAN1A2	CCI_2	Human	Cervix	CC	1.16e-02	7.60e-01	0.5249
10905	MAN1A2	CCI_3	Human	Cervix	CC	9.65e-04	6.15e-01	0.516
10905	MAN1A2	HTA11_3410_2000001011	Human	Colorectum	AD	6.65e-16	-5.52e-01	0.0155
10905	MAN1A2	HTA11_3361_2000001011	Human	Colorectum	AD	2.01e-06	-5.84e-01	-0.1207
10905	MAN1A2	HTA11_696_2000001011	Human	Colorectum	AD	1.40e-08	-3.87e-01	-0.1464
10905	MAN1A2	HTA11_866_2000001011	Human	Colorectum	AD	1.60e-02	-2.81e-01	-0.1001
10905	MAN1A2	HTA11_866_3004761011	Human	Colorectum	AD	1.55e-07	-4.78e-01	0.096
10905	MAN1A2	HTA11_10711_2000001011	Human	Colorectum	AD	6.57e-03	-4.58e-01	0.0338
10905	MAN1A2	HTA11_7696_3000711011	Human	Colorectum	AD	5.44e-09	-3.84e-01	0.0674
10905	MAN1A2	HTA11_6818_2000001021	Human	Colorectum	AD	5.16e-04	-4.52e-01	0.0588
10905	MAN1A2	HTA11_99999970781_79442	Human	Colorectum	MSS	1.55e-06	-3.85e-01	0.294
10905	MAN1A2	HTA11_99999973899_84307	Human	Colorectum	MSS	1.55e-03	-5.51e-01	0.2585
10905	MAN1A2	HTA11_99999974143_84620	Human	Colorectum	MSS	5.02e-14	-4.66e-01	0.3005
10905	MAN1A2	F007	Human	Colorectum	FAP	2.13e-02	-2.65e-01	0.1176
10905	MAN1A2	A015-C-203	Human	Colorectum	FAP	8.83e-23	-3.20e-01	-0.1294
10905	MAN1A2	A014-C-040	Human	Colorectum	FAP	3.82e-03	-4.44e-01	-0.1184
10905	MAN1A2	A002-C-201	Human	Colorectum	FAP	9.60e-09	-2.50e-01	0.0324
10905	MAN1A2	A002-C-203	Human	Colorectum	FAP	1.27e-02	-6.33e-02	0.2786
10905	MAN1A2	A001-C-119	Human	Colorectum	FAP	8.96e-03	-2.55e-01	-0.1557

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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
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
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
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:00303245	Cervix	CC	lung development	36/2311	177/18723	1.64e-03	1.26e-02	36
GO:00303235	Cervix	CC	respiratory tube development	36/2311	181/18723	2.46e-03	1.71e-02	36
GO:00605413	Cervix	CC	respiratory system development	39/2311	203/18723	3.18e-03	2.07e-02	39
GO:0006486	Colorectum	AD	protein glycosylation	64/3918	226/18723	4.86e-03	3.27e-02	64
GO:0043413	Colorectum	AD	macromolecule glycosylation	64/3918	226/18723	4.86e-03	3.27e-02	64
GO:0070085	Colorectum	AD	glycosylation	67/3918	240/18723	5.78e-03	3.67e-02	67
GO:00064861	Colorectum	FAP	protein glycosylation	48/2622	226/18723	1.85e-03	1.57e-02	48
GO:00434131	Colorectum	FAP	macromolecule glycosylation	48/2622	226/18723	1.85e-03	1.57e-02	48
GO:00700851	Colorectum	FAP	glycosylation	50/2622	240/18723	2.30e-03	1.85e-02	50
GO:0009101	Colorectum	FAP	glycoprotein biosynthetic process	63/2622	317/18723	2.31e-03	1.86e-02	63
GO:0030323	Colorectum	FAP	respiratory tube development	39/2622	181/18723	3.60e-03	2.58e-02	39
GO:0030324	Colorectum	FAP	lung development	38/2622	177/18723	4.28e-03	2.93e-02	38
GO:00303231	Colorectum	CRC	respiratory tube development	34/2078	181/18723	1.47e-03	1.57e-02	34
GO:00303241	Colorectum	CRC	lung development	33/2078	177/18723	1.94e-03	1.96e-02	33
GO:0060541	Colorectum	CRC	respiratory system development	35/2078	203/18723	5.45e-03	4.12e-02	35
GO:00091002	Esophagus	ESCC	glycoprotein metabolic process	226/8552	387/18723	2.64e-07	3.94e-06	226
GO:00700854	Esophagus	ESCC	glycosylation	144/8552	240/18723	5.12e-06	5.38e-05	144
GO:00303239	Esophagus	ESCC	respiratory tube development	112/8552	181/18723	7.82e-06	7.69e-05	112
GO:00605417	Esophagus	ESCC	respiratory system development	123/8552	203/18723	1.26e-05	1.15e-04	123
GO:00064865	Esophagus	ESCC	protein glycosylation	135/8552	226/18723	1.36e-05	1.24e-04	135

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414120	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa04141110	Cervix	CC	Protein processing in endoplasmic reticulum	55/1267	174/8465	1.74e-08	2.68e-07	1.58e-07	55
hsa04141	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa00510	Colorectum	AD	N-Glycan biosynthesis	21/2092	53/8465	1.15e-02	4.24e-02	2.71e-02	21
hsa041411	Colorectum	AD	Protein processing in endoplasmic reticulum	80/2092	174/8465	5.96e-10	1.25e-08	7.96e-09	80
hsa005101	Colorectum	AD	N-Glycan biosynthesis	21/2092	53/8465	1.15e-02	4.24e-02	2.71e-02	21
hsa041414	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa005102	Colorectum	MSS	N-Glycan biosynthesis	20/1875	53/8465	7.17e-03	2.83e-02	1.73e-02	20
hsa00513	Colorectum	MSS	Various types of N-glycan biosynthesis	16/1875	42/8465	1.39e-02	4.53e-02	2.77e-02	16
hsa041415	Colorectum	MSS	Protein processing in endoplasmic reticulum	75/1875	174/8465	3.78e-10	8.44e-09	5.17e-09	75
hsa005103	Colorectum	MSS	N-Glycan biosynthesis	20/1875	53/8465	7.17e-03	2.83e-02	1.73e-02	20
hsa005131	Colorectum	MSS	Various types of N-glycan biosynthesis	16/1875	42/8465	1.39e-02	4.53e-02	2.77e-02	16
hsa041418	Colorectum	FAP	Protein processing in endoplasmic reticulum	50/1404	174/8465	3.64e-05	3.68e-04	2.24e-04	50
hsa041419	Colorectum	FAP	Protein processing in endoplasmic reticulum	50/1404	174/8465	3.64e-05	3.68e-04	2.24e-04	50
hsa0414139	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa005106	Esophagus	HGIN	N-Glycan biosynthesis	17/1383	53/8465	3.43e-03	2.54e-02	2.02e-02	17
hsa04141114	Esophagus	HGIN	Protein processing in endoplasmic reticulum	67/1383	174/8465	1.06e-12	2.16e-11	1.72e-11	67
hsa0051013	Esophagus	HGIN	N-Glycan biosynthesis	17/1383	53/8465	3.43e-03	2.54e-02	2.02e-02	17
hsa04141211	Esophagus	ESCC	Protein processing in endoplasmic reticulum	147/4205	174/8465	3.29e-22	1.10e-19	5.64e-20	147
hsa0051023	Esophagus	ESCC	N-Glycan biosynthesis	39/4205	53/8465	3.26e-04	1.15e-03	5.89e-04	39

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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

MAN1A2

SNV

Missense_Mutation

c.1860G>T

p.Glu620Asp

p.E620D

O60476

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-A2-A25A-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Cytoxan

MAN1A2

SNV

Missense_Mutation

novel

c.62C>A

p.Pro21Gln

p.P21Q

O60476

protein_coding

deleterious(0.03)

benign(0.123)

TCGA-BH-A0HX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adrimycin

MAN1A2

insertion

In_Frame_Ins

novel

c.64_65insTTTTCTGCAGTGTGG

p.Pro22delinsLeuPheCysSerValAla

p.P22delinsLFCSVA

O60476

protein_coding

TCGA-BH-A0HX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adrimycin

MAN1A2

deletion

Frame_Shift_Del

novel

c.795delT

p.Phe265LeufsTer49

p.F265Lfs*49

O60476

protein_coding

TCGA-D8-A27V-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

MAN1A2

SNV

Missense_Mutation

novel

c.556G>A

p.Glu186Lys

p.E186K

O60476

protein_coding

tolerated(0.1)

benign(0.062)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MAN1A2

SNV

Missense_Mutation

c.226N>T

p.Pro76Ser

p.P76S

O60476

protein_coding

tolerated(0.06)

benign(0.054)

TCGA-C5-A1MH-01

Cervix

cervical & endocervical cancer

Female

>=65

III/IV

Chemotherapy

cisplatin

MAN1A2

SNV

Missense_Mutation

c.1592N>A

p.Arg531His

p.R531H

O60476

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-VS-A9UR-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MAN1A2

SNV

Missense_Mutation

c.1268A>G

p.Tyr423Cys

p.Y423C

O60476

protein_coding

deleterious(0.03)

probably_damaging(0.996)

TCGA-A6-2684-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

MAN1A2

SNV

Missense_Mutation

rs764392565

c.1088G>A

p.Arg363Gln

p.R363Q

O60476

protein_coding

deleterious(0.01)

probably_damaging(0.946)

TCGA-A6-2686-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

MAN1A2

SNV

Missense_Mutation

novel

c.1559N>G

p.Ala520Gly

p.A520G

O60476

protein_coding

deleterious(0.02)

benign(0.029)

TCGA-AA-3489-01

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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