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: MAN1A1

Gene summary for MAN1A1

Gene summary.

Gene information	Species	Human
	Gene symbol	MAN1A1
	Gene ID	4121
	Gene name	mannosidase alpha class 1A member 1
	Gene Alias	HUMM3
	Cytomap	6q22.31
	Gene Type	protein-coding
	GO ID	GO:0005975
	UniProtAcc	P33908

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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
4121	MAN1A1	NAFLD1	Human	Liver	NAFLD	8.54e-11	1.01e+00	-0.04
4121	MAN1A1	S41	Human	Liver	Cirrhotic	6.84e-04	3.09e-01	-0.0343
4121	MAN1A1	S43	Human	Liver	Cirrhotic	4.89e-07	-3.16e-02	-0.0187
4121	MAN1A1	HCC1_Meng	Human	Liver	HCC	2.46e-117	8.43e-02	0.0246
4121	MAN1A1	HCC2_Meng	Human	Liver	HCC	5.10e-20	-3.51e-01	0.0107
4121	MAN1A1	cirrhotic1	Human	Liver	Cirrhotic	2.00e-11	-3.76e-01	0.0202
4121	MAN1A1	cirrhotic2	Human	Liver	Cirrhotic	3.41e-11	-2.29e-01	0.0201
4121	MAN1A1	cirrhotic3	Human	Liver	Cirrhotic	5.99e-05	-3.24e-01	0.0215
4121	MAN1A1	HCC1	Human	Liver	HCC	2.37e-21	5.22e+00	0.5336
4121	MAN1A1	HCC2	Human	Liver	HCC	1.63e-17	3.71e+00	0.5341
4121	MAN1A1	Pt13.a	Human	Liver	HCC	4.58e-05	-2.25e-01	0.021
4121	MAN1A1	Pt13.b	Human	Liver	HCC	2.93e-14	-2.26e-01	0.0251
4121	MAN1A1	Pt14.a	Human	Liver	HCC	2.65e-10	1.84e-01	0.0169
4121	MAN1A1	Pt14.d	Human	Liver	HCC	2.78e-05	-2.03e-01	0.0143
4121	MAN1A1	S027	Human	Liver	HCC	3.93e-04	5.23e-01	0.2446
4121	MAN1A1	S028	Human	Liver	HCC	1.41e-10	5.21e-01	0.2503
4121	MAN1A1	S029	Human	Liver	HCC	9.99e-08	6.97e-01	0.2581
4121	MAN1A1	C30	Human	Oral cavity	OSCC	4.83e-23	1.47e+00	0.3055
4121	MAN1A1	EOLP-1	Human	Oral cavity	EOLP	2.56e-12	5.59e-01	-0.0202
4121	MAN1A1	NEOLP-1	Human	Oral cavity	NEOLP	1.96e-18	7.55e-01	-0.0194

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		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

∗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:00431617	Liver	NAFLD	proteasome-mediated ubiquitin-dependent protein catabolic process	91/1882	412/18723	3.00e-13	1.75e-10	91
GO:00104987	Liver	NAFLD	proteasomal protein catabolic process	101/1882	490/18723	1.35e-12	6.09e-10	101
GO:0006517	Liver	NAFLD	protein deglycosylation	9/1882	26/18723	6.56e-04	8.50e-03	9
GO:00725947	Liver	NAFLD	establishment of protein localization to organelle	62/1882	422/18723	1.48e-03	1.64e-02	62
GO:0036507	Liver	NAFLD	protein demannosylation	6/1882	18/18723	6.55e-03	4.69e-02	6
GO:0036508	Liver	NAFLD	protein alpha-1,2-demannosylation	6/1882	18/18723	6.55e-03	4.69e-02	6
GO:001049812	Liver	Cirrhotic	proteasomal protein catabolic process	216/4634	490/18723	2.52e-21	9.29e-19	216
GO:007259412	Liver	Cirrhotic	establishment of protein localization to organelle	189/4634	422/18723	1.01e-19	2.45e-17	189
GO:00349767	Liver	Cirrhotic	response to endoplasmic reticulum stress	130/4634	256/18723	1.72e-19	3.86e-17	130
GO:004316112	Liver	Cirrhotic	proteasome-mediated ubiquitin-dependent protein catabolic process	184/4634	412/18723	4.52e-19	8.85e-17	184
GO:00066057	Liver	Cirrhotic	protein targeting	148/4634	314/18723	3.86e-18	6.20e-16	148
GO:00709724	Liver	Cirrhotic	protein localization to endoplasmic reticulum	45/4634	74/18723	4.79e-11	2.73e-09	45
GO:0030433	Liver	Cirrhotic	ubiquitin-dependent ERAD pathway	45/4634	85/18723	2.19e-08	7.75e-07	45
GO:00365032	Liver	Cirrhotic	ERAD pathway	53/4634	107/18723	2.58e-08	8.89e-07	53
GO:00725994	Liver	Cirrhotic	establishment of protein localization to endoplasmic reticulum	26/4634	46/18723	4.14e-06	6.94e-05	26
GO:00450474	Liver	Cirrhotic	protein targeting to ER	24/4634	42/18723	7.49e-06	1.15e-04	24
GO:00065171	Liver	Cirrhotic	protein deglycosylation	14/4634	26/18723	1.37e-03	9.14e-03	14
GO:00365071	Liver	Cirrhotic	protein demannosylation	10/4634	18/18723	5.00e-03	2.59e-02	10
GO:00365081	Liver	Cirrhotic	protein alpha-1,2-demannosylation	10/4634	18/18723	5.00e-03	2.59e-02	10
GO:001049822	Liver	HCC	proteasomal protein catabolic process	351/7958	490/18723	6.92e-40	1.46e-36	351

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa0414114	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa005104	Liver	Cirrhotic	N-Glycan biosynthesis	32/2530	53/8465	3.82e-06	4.10e-05	2.53e-05	32
hsa005134	Liver	Cirrhotic	Various types of N-glycan biosynthesis	26/2530	42/8465	1.65e-05	1.41e-04	8.69e-05	26
hsa0414115	Liver	Cirrhotic	Protein processing in endoplasmic reticulum	114/2530	174/8465	1.16e-22	9.67e-21	5.96e-21	114
hsa0051011	Liver	Cirrhotic	N-Glycan biosynthesis	32/2530	53/8465	3.82e-06	4.10e-05	2.53e-05	32
hsa0051311	Liver	Cirrhotic	Various types of N-glycan biosynthesis	26/2530	42/8465	1.65e-05	1.41e-04	8.69e-05	26
hsa0414122	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0051021	Liver	HCC	N-Glycan biosynthesis	40/4020	53/8465	2.95e-05	1.87e-04	1.04e-04	40
hsa005132	Liver	HCC	Various types of N-glycan biosynthesis	30/4020	42/8465	1.41e-03	5.07e-03	2.82e-03	30
hsa0414132	Liver	HCC	Protein processing in endoplasmic reticulum	146/4020	174/8465	7.34e-24	2.46e-21	1.37e-21	146
hsa0051031	Liver	HCC	N-Glycan biosynthesis	40/4020	53/8465	2.95e-05	1.87e-04	1.04e-04	40
hsa005133	Liver	HCC	Various types of N-glycan biosynthesis	30/4020	42/8465	1.41e-03	5.07e-03	2.82e-03	30
hsa0414130	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa005105	Oral cavity	OSCC	N-Glycan biosynthesis	39/3704	53/8465	9.77e-06	4.36e-05	2.22e-05	39
hsa005135	Oral cavity	OSCC	Various types of N-glycan biosynthesis	29/3704	42/8465	8.03e-04	2.32e-03	1.18e-03	29
hsa04141113	Oral cavity	OSCC	Protein processing in endoplasmic reticulum	143/3704	174/8465	6.82e-26	2.28e-23	1.16e-23	143
hsa0051012	Oral cavity	OSCC	N-Glycan biosynthesis	39/3704	53/8465	9.77e-06	4.36e-05	2.22e-05	39
hsa0051312	Oral cavity	OSCC	Various types of N-glycan biosynthesis	29/3704	42/8465	8.03e-04	2.32e-03	1.18e-03	29
hsa0414145	Oral cavity	EOLP	Protein processing in endoplasmic reticulum	70/1218	174/8465	2.84e-17	3.06e-15	1.81e-15	70
hsa0414155	Oral cavity	EOLP	Protein processing in endoplasmic reticulum	70/1218	174/8465	2.84e-17	3.06e-15	1.81e-15	70

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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

MAN1A1

SNV

Missense_Mutation

c.838G>A

p.Glu280Lys

p.E280K

P33908

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-A7-A56D-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

MAN1A1

SNV

Missense_Mutation

novel

c.1541G>A

p.Arg514Gln

p.R514Q

P33908

protein_coding

deleterious(0)

probably_damaging(0.978)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MAN1A1

SNV

Missense_Mutation

novel

c.655G>A

p.Glu219Lys

p.E219K

P33908

protein_coding

deleterious(0.01)

probably_damaging(0.964)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MAN1A1

SNV

Missense_Mutation

rs199809553

c.1913N>C

p.Leu638Pro

p.L638P

P33908

protein_coding

deleterious(0)

probably_damaging(0.98)

TCGA-AO-A124-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

MAN1A1

SNV

Missense_Mutation

c.1122G>A

p.Met374Ile

p.M374I

P33908

protein_coding

tolerated(0.2)

benign(0.156)

TCGA-B6-A0WZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

MAN1A1

SNV

Missense_Mutation

c.1567N>A

p.Ala523Thr

p.A523T

P33908

protein_coding

deleterious(0.03)

probably_damaging(0.936)

TCGA-BH-A0HF-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

MAN1A1

SNV

Missense_Mutation

c.1415N>A

p.Gly472Asp

p.G472D

P33908

protein_coding

tolerated(0.57)

probably_damaging(1)

TCGA-D8-A1J8-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

nolvadex

MAN1A1

SNV

Missense_Mutation

novel

c.1066N>C

p.Glu356Gln

p.E356Q

P33908

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-PL-A8LV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

MAN1A1

SNV

Missense_Mutation

novel

c.1019C>T

p.Ala340Val

p.A340V

P33908

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MAN1A1

SNV

Missense_Mutation

c.1111G>A

p.Glu371Lys

p.E371K

P33908

protein_coding

tolerated(0.12)

benign(0.022)

TCGA-IR-A3LK-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

cisplatin

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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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