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: MLXIP

Gene summary for MLXIP

Gene summary.

Gene information	Species	Human
	Gene symbol	MLXIP
	Gene ID	22877
	Gene name	MLX interacting protein
	Gene Alias	MIR
	Cytomap	12q24.31
	Gene Type	protein-coding
	GO ID	GO:0006139
	UniProtAcc	Q9HAP2

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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
22877	MLXIP	HTA11_3410_2000001011	Human	Colorectum	AD	2.43e-13	6.30e-01	0.0155
22877	MLXIP	HTA11_2951_2000001011	Human	Colorectum	AD	9.74e-08	8.67e-01	0.0216
22877	MLXIP	HTA11_1938_2000001011	Human	Colorectum	AD	3.40e-10	6.98e-01	-0.0811
22877	MLXIP	HTA11_347_2000001011	Human	Colorectum	AD	1.56e-31	1.07e+00	-0.1954
22877	MLXIP	HTA11_3361_2000001011	Human	Colorectum	AD	1.22e-05	6.16e-01	-0.1207
22877	MLXIP	HTA11_83_2000001011	Human	Colorectum	SER	2.74e-09	8.92e-01	-0.1526
22877	MLXIP	HTA11_696_2000001011	Human	Colorectum	AD	2.51e-11	6.81e-01	-0.1464
22877	MLXIP	HTA11_866_2000001011	Human	Colorectum	AD	1.08e-05	4.82e-01	-0.1001
22877	MLXIP	HTA11_1391_2000001011	Human	Colorectum	AD	2.78e-03	5.33e-01	-0.059
22877	MLXIP	HTA11_2992_2000001011	Human	Colorectum	SER	3.60e-03	6.00e-01	-0.1706
22877	MLXIP	HTA11_5212_2000001011	Human	Colorectum	AD	1.47e-02	4.97e-01	-0.2061
22877	MLXIP	HTA11_5216_2000001011	Human	Colorectum	SER	4.67e-04	5.79e-01	-0.1462
22877	MLXIP	HTA11_546_2000001011	Human	Colorectum	AD	9.97e-15	1.02e+00	-0.0842
22877	MLXIP	HTA11_9341_2000001011	Human	Colorectum	SER	1.89e-02	4.64e-01	-0.00410000000000005
22877	MLXIP	HTA11_7862_2000001011	Human	Colorectum	AD	7.48e-15	8.46e-01	-0.0179
22877	MLXIP	HTA11_4255_2000001011	Human	Colorectum	SER	9.56e-04	6.16e-01	0.0446
22877	MLXIP	HTA11_9408_2000001011	Human	Colorectum	AD	2.77e-11	8.65e-01	0.0451
22877	MLXIP	HTA11_7663_2000001011	Human	Colorectum	SER	2.40e-14	1.19e+00	0.0131
22877	MLXIP	HTA11_10623_2000001011	Human	Colorectum	AD	1.07e-21	1.34e+00	-0.0177
22877	MLXIP	HTA11_6801_2000001011	Human	Colorectum	SER	1.24e-08	8.11e-01	0.0171

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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
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:00020822	Liver	Cirrhotic	regulation of oxidative phosphorylation	12/4634	23/18723	4.23e-03	2.24e-02	12
GO:19005423	Liver	Cirrhotic	regulation of purine nucleotide metabolic process	32/4634	84/18723	4.53e-03	2.40e-02	32
GO:0033137	Liver	Cirrhotic	negative regulation of peptidyl-serine phosphorylation	14/4634	30/18723	7.40e-03	3.53e-02	14
GO:19035794	Liver	Cirrhotic	negative regulation of ATP metabolic process	14/4634	30/18723	7.40e-03	3.53e-02	14
GO:00550901	Liver	Cirrhotic	acylglycerol homeostasis	18/4634	42/18723	7.64e-03	3.61e-02	18
GO:00703281	Liver	Cirrhotic	triglyceride homeostasis	18/4634	42/18723	7.64e-03	3.61e-02	18
GO:0045923	Liver	Cirrhotic	positive regulation of fatty acid metabolic process	17/4634	39/18723	7.71e-03	3.63e-02	17
GO:00423043	Liver	Cirrhotic	regulation of fatty acid biosynthetic process	20/4634	49/18723	9.60e-03	4.35e-02	20
GO:000609122	Liver	HCC	generation of precursor metabolites and energy	340/7958	490/18723	4.04e-34	2.85e-31	340
GO:000989622	Liver	HCC	positive regulation of catabolic process	335/7958	492/18723	3.83e-31	1.87e-28	335
GO:003133122	Liver	HCC	positive regulation of cellular catabolic process	295/7958	427/18723	3.20e-29	1.45e-26	295
GO:000906012	Liver	HCC	aerobic respiration	147/7958	189/18723	3.13e-23	6.61e-21	147
GO:004533312	Liver	HCC	cellular respiration	171/7958	230/18723	6.35e-23	1.26e-20	171
GO:004603422	Liver	HCC	ATP metabolic process	198/7958	277/18723	8.30e-23	1.55e-20	198
GO:001598022	Liver	HCC	energy derivation by oxidation of organic compounds	221/7958	318/18723	1.02e-22	1.86e-20	221
GO:000611912	Liver	HCC	oxidative phosphorylation	110/7958	141/18723	6.58e-18	7.45e-16	110
GO:000911722	Liver	HCC	nucleotide metabolic process	300/7958	489/18723	1.61e-17	1.71e-15	300
GO:000675322	Liver	HCC	nucleoside phosphate metabolic process	304/7958	497/18723	1.78e-17	1.85e-15	304
GO:001969322	Liver	HCC	ribose phosphate metabolic process	248/7958	396/18723	3.15e-16	2.70e-14	248
GO:000925922	Liver	HCC	ribonucleotide metabolic process	240/7958	385/18723	2.07e-15	1.51e-13	240

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04932	Colorectum	AD	Non-alcoholic fatty liver disease	90/2092	155/8465	4.83e-19	1.80e-17	1.15e-17	90
hsa049321	Colorectum	AD	Non-alcoholic fatty liver disease	90/2092	155/8465	4.83e-19	1.80e-17	1.15e-17	90
hsa049322	Colorectum	SER	Non-alcoholic fatty liver disease	75/1580	155/8465	2.16e-17	5.99e-16	4.35e-16	75
hsa049323	Colorectum	SER	Non-alcoholic fatty liver disease	75/1580	155/8465	2.16e-17	5.99e-16	4.35e-16	75
hsa049324	Colorectum	MSS	Non-alcoholic fatty liver disease	85/1875	155/8465	4.19e-19	1.17e-17	7.17e-18	85
hsa04931	Colorectum	MSS	Insulin resistance	36/1875	108/8465	4.74e-03	2.01e-02	1.23e-02	36
hsa049325	Colorectum	MSS	Non-alcoholic fatty liver disease	85/1875	155/8465	4.19e-19	1.17e-17	7.17e-18	85
hsa049311	Colorectum	MSS	Insulin resistance	36/1875	108/8465	4.74e-03	2.01e-02	1.23e-02	36
hsa049326	Colorectum	MSI-H	Non-alcoholic fatty liver disease	52/797	155/8465	4.61e-17	1.49e-15	1.25e-15	52
hsa049327	Colorectum	MSI-H	Non-alcoholic fatty liver disease	52/797	155/8465	4.61e-17	1.49e-15	1.25e-15	52
hsa049328	Colorectum	FAP	Non-alcoholic fatty liver disease	54/1404	155/8465	1.98e-08	6.20e-07	3.77e-07	54
hsa049312	Colorectum	FAP	Insulin resistance	32/1404	108/8465	4.90e-04	3.56e-03	2.16e-03	32
hsa049329	Colorectum	FAP	Non-alcoholic fatty liver disease	54/1404	155/8465	1.98e-08	6.20e-07	3.77e-07	54
hsa049313	Colorectum	FAP	Insulin resistance	32/1404	108/8465	4.90e-04	3.56e-03	2.16e-03	32
hsa049314	Colorectum	CRC	Insulin resistance	28/1091	108/8465	1.78e-04	2.37e-03	1.61e-03	28
hsa049315	Colorectum	CRC	Insulin resistance	28/1091	108/8465	1.78e-04	2.37e-03	1.61e-03	28
hsa04932210	Esophagus	ESCC	Non-alcoholic fatty liver disease	122/4205	155/8465	5.69e-14	1.59e-12	8.14e-13	122
hsa049318	Esophagus	ESCC	Insulin resistance	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69
hsa0493238	Esophagus	ESCC	Non-alcoholic fatty liver disease	122/4205	155/8465	5.69e-14	1.59e-12	8.14e-13	122
hsa0493113	Esophagus	ESCC	Insulin resistance	69/4205	108/8465	1.92e-03	5.54e-03	2.84e-03	69

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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

TF	Cell Type	Tissue	Disease Stage	Target Gene	RSS	Regulon Activity
MLXIP	CAF	Breast	ADJ	NEAT1,KRT6B,SOX9, etc.	9.09e-02
MLXIP	BAS	Cervix	Healthy	KRAS,NAPB,PICALM, etc.	2.72e-01
MLXIP	ABS	Colorectum	FAP	SELENBP1,ADAMTSL1,AC103702.2, etc.	1.76e-01
MLXIP	DUCT2	Pancreas	ADJ	NTN4,ZNF335,UBR1, etc.	4.05e-03

∗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

MLXIP

SNV

Missense_Mutation

rs528028662

c.2651C>T

p.Thr884Met

p.T884M

Q9HAP2

protein_coding

deleterious(0)

probably_damaging(0.953)

TCGA-A2-A0T1-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Targeted Molecular therapy

herceptin

MLXIP

SNV

Missense_Mutation

novel

c.727N>G

p.Ser243Gly

p.S243G

Q9HAP2

protein_coding

deleterious(0.01)

possibly_damaging(0.852)

TCGA-BH-A0AY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

MLXIP

SNV

Missense_Mutation

c.374C>G

p.Ser125Trp

p.S125W

Q9HAP2

protein_coding

deleterious(0)

probably_damaging(0.942)

TCGA-D8-A1JA-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

MLXIP

SNV

Missense_Mutation

c.225N>C

p.Gln75His

p.Q75H

Q9HAP2

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-E2-A159-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

MLXIP

SNV

Missense_Mutation

rs202216030

c.2362N>A

p.Glu788Lys

p.E788K

Q9HAP2

protein_coding

deleterious(0)

probably_damaging(0.99)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MLXIP

SNV

Missense_Mutation

novel

c.2709N>T

p.Glu903Asp

p.E903D

Q9HAP2

protein_coding

tolerated(0.07)

possibly_damaging(0.53)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

MLXIP

SNV

Missense_Mutation

c.1480N>T

p.His494Tyr

p.H494Y

Q9HAP2

protein_coding

tolerated(0.06)

possibly_damaging(0.899)

TCGA-C5-A3HL-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Unknown

MLXIP

SNV

Missense_Mutation

novel

c.1159N>T

p.Thr387Ser

p.T387S

Q9HAP2

protein_coding

tolerated(0.59)

benign(0.009)

TCGA-DS-A1OA-01

Cervix

cervical & endocervical cancer

Female

>=65

I/II

Chemotherapy

carboplatin

MLXIP

SNV

Missense_Mutation

c.2131C>T

p.Pro711Ser

p.P711S

Q9HAP2

protein_coding

tolerated(0.32)

benign(0.001)

TCGA-AA-3492-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

MLXIP

SNV

Missense_Mutation

c.901N>T

p.Arg301Trp

p.R301W

Q9HAP2

protein_coding

deleterious(0)

probably_damaging(0.982)

TCGA-AD-5900-01

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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