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: MFSD6

Gene summary for MFSD6

Gene summary.

Gene information	Species	Human
	Gene symbol	MFSD6
	Gene ID	54842
	Gene name	major facilitator superfamily domain containing 6
	Gene Alias	MMR2
	Cytomap	2q32.2
	Gene Type	protein-coding
	GO ID	GO:0002376
	UniProtAcc	Q6ZSS7

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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
54842	MFSD6	LZE4T	Human	Esophagus	ESCC	2.46e-03	6.50e-02	0.0811
54842	MFSD6	LZE24T	Human	Esophagus	ESCC	1.31e-10	1.05e-01	0.0596
54842	MFSD6	P2T-E	Human	Esophagus	ESCC	2.21e-11	5.16e-02	0.1177
54842	MFSD6	P4T-E	Human	Esophagus	ESCC	6.82e-12	2.32e-01	0.1323
54842	MFSD6	P5T-E	Human	Esophagus	ESCC	1.33e-10	1.92e-02	0.1327
54842	MFSD6	P8T-E	Human	Esophagus	ESCC	6.03e-14	1.31e-01	0.0889
54842	MFSD6	P9T-E	Human	Esophagus	ESCC	4.44e-09	2.19e-01	0.1131
54842	MFSD6	P10T-E	Human	Esophagus	ESCC	5.09e-11	1.83e-01	0.116
54842	MFSD6	P11T-E	Human	Esophagus	ESCC	3.45e-05	8.51e-02	0.1426
54842	MFSD6	P12T-E	Human	Esophagus	ESCC	2.01e-17	2.05e-01	0.1122
54842	MFSD6	P15T-E	Human	Esophagus	ESCC	1.64e-17	2.88e-01	0.1149
54842	MFSD6	P16T-E	Human	Esophagus	ESCC	3.75e-07	3.46e-02	0.1153
54842	MFSD6	P17T-E	Human	Esophagus	ESCC	2.47e-02	1.46e-01	0.1278
54842	MFSD6	P20T-E	Human	Esophagus	ESCC	8.09e-18	2.93e-01	0.1124
54842	MFSD6	P21T-E	Human	Esophagus	ESCC	5.27e-18	4.03e-01	0.1617
54842	MFSD6	P22T-E	Human	Esophagus	ESCC	3.77e-09	1.26e-01	0.1236
54842	MFSD6	P23T-E	Human	Esophagus	ESCC	9.42e-40	1.12e+00	0.108
54842	MFSD6	P24T-E	Human	Esophagus	ESCC	2.10e-11	1.16e-01	0.1287
54842	MFSD6	P26T-E	Human	Esophagus	ESCC	2.19e-06	9.37e-02	0.1276
54842	MFSD6	P27T-E	Human	Esophagus	ESCC	6.06e-10	6.30e-02	0.1055

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
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:004800220	Esophagus	ESCC	antigen processing and presentation of peptide antigen	44/8552	62/18723	4.81e-05	3.78e-04	44
GO:000247820	Esophagus	ESCC	antigen processing and presentation of exogenous peptide antigen	29/8552	38/18723	1.18e-04	8.13e-04	29
GO:001988225	Esophagus	ESCC	antigen processing and presentation	67/8552	106/18723	2.03e-04	1.28e-03	67
GO:000247418	Esophagus	ESCC	antigen processing and presentation of peptide antigen via MHC class I	22/8552	28/18723	3.95e-04	2.26e-03	22
GO:001988420	Esophagus	ESCC	antigen processing and presentation of exogenous antigen	33/8552	47/18723	5.77e-04	3.14e-03	33
GO:001988220	Oral cavity	OSCC	antigen processing and presentation	65/7305	106/18723	2.69e-06	3.32e-05	65
GO:004800219	Oral cavity	OSCC	antigen processing and presentation of peptide antigen	40/7305	62/18723	4.20e-05	3.63e-04	40
GO:000247416	Oral cavity	OSCC	antigen processing and presentation of peptide antigen via MHC class I	21/7305	28/18723	1.19e-04	8.54e-04	21
GO:000247819	Oral cavity	OSCC	antigen processing and presentation of exogenous peptide antigen	26/7305	38/18723	2.29e-04	1.49e-03	26
GO:001988419	Oral cavity	OSCC	antigen processing and presentation of exogenous antigen	30/7305	47/18723	4.96e-04	2.92e-03	30
GO:0019882110	Oral cavity	LP	antigen processing and presentation	48/4623	106/18723	2.96e-06	6.44e-05	48
GO:0048002110	Oral cavity	LP	antigen processing and presentation of peptide antigen	30/4623	62/18723	4.46e-05	6.35e-04	30
GO:0002478110	Oral cavity	LP	antigen processing and presentation of exogenous peptide antigen	20/4623	38/18723	1.95e-04	2.15e-03	20
GO:000247417	Oral cavity	LP	antigen processing and presentation of peptide antigen via MHC class I	16/4623	28/18723	2.46e-04	2.60e-03	16
GO:0019884110	Oral cavity	LP	antigen processing and presentation of exogenous antigen	22/4623	47/18723	8.02e-04	7.05e-03	22
GO:0019882112	Thyroid	PTC	antigen processing and presentation	57/5968	106/18723	2.40e-06	3.17e-05	57
GO:0002478112	Thyroid	PTC	antigen processing and presentation of exogenous peptide antigen	25/5968	38/18723	1.80e-05	1.86e-04	25
GO:0048002112	Thyroid	PTC	antigen processing and presentation of peptide antigen	36/5968	62/18723	1.84e-05	1.89e-04	36
GO:0019884112	Thyroid	PTC	antigen processing and presentation of exogenous antigen	29/5968	47/18723	2.44e-05	2.40e-04	29
GO:0002474110	Thyroid	PTC	antigen processing and presentation of peptide antigen via MHC class I	19/5968	28/18723	9.95e-05	8.15e-04	19

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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

MFSD6

SNV

Missense_Mutation

c.1153N>T

p.Val385Phe

p.V385F

Q6ZSS7

protein_coding

deleterious(0)

probably_damaging(0.985)

TCGA-A7-A0CE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

MFSD6

SNV

Missense_Mutation

novel

c.1712N>G

p.Gln571Arg

p.Q571R

Q6ZSS7

protein_coding

deleterious(0)

probably_damaging(0.955)

TCGA-A8-A08L-01

Breast

breast invasive carcinoma

Female

>=65

III/IV

Unknown

MFSD6

SNV

Missense_Mutation

rs202101969

c.1054N>A

p.Glu352Lys

p.E352K

Q6ZSS7

protein_coding

tolerated(0.62)

benign(0.017)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

MFSD6

insertion

Nonsense_Mutation

novel

c.1155_1156insTAAATTTTACTTTACA

p.Ala386Ter

p.A386*

Q6ZSS7

protein_coding

TCGA-A7-A0CE-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

MFSD6

SNV

Missense_Mutation

c.560N>G

p.Ser187Cys

p.S187C

Q6ZSS7

protein_coding

deleterious(0.03)

benign(0.161)

TCGA-BI-A0VS-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

MFSD6

SNV

Missense_Mutation

novel

c.2240C>G

p.Ser747Cys

p.S747C

Q6ZSS7

protein_coding

deleterious_low_confidence(0.03)

benign(0.159)

TCGA-HM-A4S6-01

Cervix

cervical & endocervical cancer

Female

<65

III/IV

Chemotherapy

cisplatin

MFSD6

SNV

Missense_Mutation

rs760269189

c.1090G>A

p.Glu364Lys

p.E364K

Q6ZSS7

protein_coding

tolerated(0.11)

benign(0.318)

TCGA-AA-3947-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

MFSD6

SNV

Missense_Mutation

novel

c.642G>T

p.Leu214Phe

p.L214F

Q6ZSS7

protein_coding

tolerated(0.85)

benign(0)

TCGA-AA-3949-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Unknown

MFSD6

SNV

Missense_Mutation

c.586C>T

p.Arg196Cys

p.R196C

Q6ZSS7

protein_coding

deleterious(0.01)

possibly_damaging(0.614)

TCGA-AZ-4616-01

Colorectum

colon adenocarcinoma

Female

>=65

III/IV

Chemotherapy

xeloda

MFSD6

SNV

Missense_Mutation

novel

c.2198N>A

p.Ser733Tyr

p.S733Y

Q6ZSS7

protein_coding

deleterious_low_confidence(0.01)

benign(0.003)

TCGA-CA-6717-01

Colorectum

colon adenocarcinoma

Male

<65

I/II

Chemotherapy

oxaliplatin

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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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