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	LZE8T	Human	Esophagus	ESCC	6.97e-07	9.96e-02	0.067
22877	MLXIP	LZE24T	Human	Esophagus	ESCC	3.18e-08	1.56e-01	0.0596
22877	MLXIP	P1T-E	Human	Esophagus	ESCC	1.08e-07	3.40e-01	0.0875
22877	MLXIP	P2T-E	Human	Esophagus	ESCC	5.07e-33	6.78e-01	0.1177
22877	MLXIP	P4T-E	Human	Esophagus	ESCC	7.96e-21	2.66e-01	0.1323
22877	MLXIP	P5T-E	Human	Esophagus	ESCC	4.27e-19	2.94e-01	0.1327
22877	MLXIP	P8T-E	Human	Esophagus	ESCC	4.95e-27	4.97e-01	0.0889
22877	MLXIP	P9T-E	Human	Esophagus	ESCC	1.54e-12	2.47e-01	0.1131
22877	MLXIP	P10T-E	Human	Esophagus	ESCC	3.16e-22	3.44e-01	0.116
22877	MLXIP	P11T-E	Human	Esophagus	ESCC	1.56e-12	4.19e-01	0.1426
22877	MLXIP	P12T-E	Human	Esophagus	ESCC	3.54e-07	8.03e-02	0.1122
22877	MLXIP	P15T-E	Human	Esophagus	ESCC	7.53e-19	1.24e-01	0.1149
22877	MLXIP	P16T-E	Human	Esophagus	ESCC	3.58e-11	1.82e-01	0.1153
22877	MLXIP	P17T-E	Human	Esophagus	ESCC	5.75e-11	3.15e-01	0.1278
22877	MLXIP	P20T-E	Human	Esophagus	ESCC	3.37e-11	3.51e-02	0.1124
22877	MLXIP	P21T-E	Human	Esophagus	ESCC	6.10e-16	1.69e-01	0.1617
22877	MLXIP	P22T-E	Human	Esophagus	ESCC	7.64e-16	9.03e-02	0.1236
22877	MLXIP	P23T-E	Human	Esophagus	ESCC	3.82e-20	3.88e-01	0.108
22877	MLXIP	P24T-E	Human	Esophagus	ESCC	1.94e-14	5.27e-02	0.1287
22877	MLXIP	P26T-E	Human	Esophagus	ESCC	4.74e-22	1.79e-01	0.1276

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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:0046034	Colorectum	AD	ATP metabolic process	142/3918	277/18723	2.64e-29	8.26e-26	142
GO:0006091	Colorectum	AD	generation of precursor metabolites and energy	209/3918	490/18723	3.17e-28	6.61e-25	209
GO:0009060	Colorectum	AD	aerobic respiration	108/3918	189/18723	9.14e-28	1.43e-24	108
GO:0045333	Colorectum	AD	cellular respiration	119/3918	230/18723	3.21e-25	4.02e-22	119
GO:0006119	Colorectum	AD	oxidative phosphorylation	83/3918	141/18723	7.95e-23	8.30e-20	83
GO:0015980	Colorectum	AD	energy derivation by oxidation of organic compounds	143/3918	318/18723	2.78e-22	2.49e-19	143
GO:0009896	Colorectum	AD	positive regulation of catabolic process	180/3918	492/18723	4.33e-16	1.94e-13	180
GO:0009150	Colorectum	AD	purine ribonucleotide metabolic process	142/3918	368/18723	4.29e-15	1.17e-12	142
GO:0006163	Colorectum	AD	purine nucleotide metabolic process	149/3918	396/18723	1.08e-14	2.80e-12	149
GO:0072521	Colorectum	AD	purine-containing compound metabolic process	153/3918	416/18723	4.34e-14	1.01e-11	153
GO:0031331	Colorectum	AD	positive regulation of cellular catabolic process	156/3918	427/18723	4.68e-14	1.05e-11	156
GO:0009259	Colorectum	AD	ribonucleotide metabolic process	144/3918	385/18723	5.25e-14	1.13e-11	144
GO:0019693	Colorectum	AD	ribose phosphate metabolic process	145/3918	396/18723	3.01e-13	5.71e-11	145
GO:0009117	Colorectum	AD	nucleotide metabolic process	168/3918	489/18723	2.20e-12	3.36e-10	168
GO:0006753	Colorectum	AD	nucleoside phosphate metabolic process	169/3918	497/18723	4.99e-12	6.98e-10	169
GO:0009135	Colorectum	AD	purine nucleoside diphosphate metabolic process	47/3918	103/18723	1.61e-08	9.22e-07	47
GO:0009179	Colorectum	AD	purine ribonucleoside diphosphate metabolic process	47/3918	103/18723	1.61e-08	9.22e-07	47
GO:0006090	Colorectum	AD	pyruvate metabolic process	47/3918	106/18723	4.85e-08	2.55e-06	47
GO:0009185	Colorectum	AD	ribonucleoside diphosphate metabolic process	47/3918	106/18723	4.85e-08	2.55e-06	47
GO:0046031	Colorectum	AD	ADP metabolic process	41/3918	90/18723	1.37e-07	6.42e-06	41

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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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