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: LIN28A

Gene summary for LIN28A

Gene summary.

Gene information	Species	Human
	Gene symbol	LIN28A
	Gene ID	79727
	Gene name	lin-28 homolog A
	Gene Alias	CSDD1
	Cytomap	1p36.11
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	Q9H9Z2

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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
79727	LIN28A	HCC1	Human	Liver	HCC	1.17e-09	7.06e-01	0.5336
79727	LIN28A	HCC2	Human	Liver	HCC	3.10e-11	7.14e-01	0.5341
79727	LIN28A	HCC5	Human	Liver	HCC	8.91e-07	4.16e-01	0.4932
79727	LIN28A	S015	Human	Liver	HCC	2.74e-02	1.69e-01	0.2375

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Liver		HCC: Hepatocellular carcinoma
Liver		NAFLD: Non-alcoholic fatty liver disease

∗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:00344702	Liver	HCC	ncRNA processing	293/7958	395/18723	4.26e-38	6.76e-35	293
GO:000218122	Liver	HCC	cytoplasmic translation	132/7958	148/18723	9.09e-33	5.76e-30	132
GO:00346601	Liver	HCC	ncRNA metabolic process	332/7958	485/18723	1.48e-31	7.80e-29	332
GO:004427021	Liver	HCC	cellular nitrogen compound catabolic process	303/7958	451/18723	9.76e-27	3.64e-24	303
GO:004670021	Liver	HCC	heterocycle catabolic process	299/7958	445/18723	2.07e-26	7.29e-24	299
GO:190136121	Liver	HCC	organic cyclic compound catabolic process	325/7958	495/18723	6.52e-26	2.18e-23	325
GO:001943921	Liver	HCC	aromatic compound catabolic process	309/7958	467/18723	1.56e-25	4.94e-23	309
GO:000640121	Liver	HCC	RNA catabolic process	201/7958	278/18723	3.88e-24	1.02e-21	201
GO:003465521	Liver	HCC	nucleobase-containing compound catabolic process	273/7958	407/18723	4.84e-24	1.23e-21	273
GO:000641722	Liver	HCC	regulation of translation	287/7958	468/18723	8.79e-17	8.08e-15	287
GO:004572712	Liver	HCC	positive regulation of translation	97/7958	136/18723	8.51e-12	3.55e-10	97
GO:003425022	Liver	HCC	positive regulation of cellular amide metabolic process	110/7958	162/18723	5.14e-11	1.92e-09	110
GO:00311231	Liver	HCC	RNA 3'-end processing	81/7958	116/18723	2.27e-09	6.32e-08	81
GO:000974322	Liver	HCC	response to carbohydrate	149/7958	253/18723	9.55e-08	1.89e-06	149
GO:003428422	Liver	HCC	response to monosaccharide	131/7958	225/18723	1.32e-06	1.91e-05	131
GO:000974622	Liver	HCC	response to hexose	126/7958	219/18723	4.81e-06	6.06e-05	126
GO:00319291	Liver	HCC	TOR signaling	78/7958	126/18723	8.49e-06	9.97e-05	78
GO:000974912	Liver	HCC	response to glucose	121/7958	212/18723	1.24e-05	1.39e-04	121
GO:003105021	Liver	HCC	dsRNA processing	38/7958	54/18723	3.15e-05	3.21e-04	38
GO:007091821	Liver	HCC	production of small RNA involved in gene silencing by RNA	38/7958	54/18723	3.15e-05	3.21e-04	38

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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

LIN28A

SNV

Missense_Mutation

novel

c.50N>A

p.Ala17Glu

p.A17E

Q9H9Z2

protein_coding

tolerated(0.88)

benign(0.007)

TCGA-BH-A0BR-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

LIN28A

SNV

Missense_Mutation

novel

c.473N>T

p.Pro158Leu

p.P158L

Q9H9Z2

protein_coding

deleterious(0)

probably_damaging(0.996)

TCGA-OL-A5RZ-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

doxorubicin

LIN28A

SNV

Missense_Mutation

rs748187241

c.575G>A

p.Arg192Gln

p.R192Q

Q9H9Z2

protein_coding

tolerated_low_confidence(0.48)

benign(0.006)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

LIN28A

SNV

Missense_Mutation

c.297G>C

p.Lys99Asn

p.K99N

Q9H9Z2

protein_coding

tolerated(0.07)

probably_damaging(0.997)

TCGA-AD-6901-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Chemotherapy

xeloda

LIN28A

SNV

Missense_Mutation

c.148N>T

p.Arg50Cys

p.R50C

Q9H9Z2

protein_coding

tolerated(0.1)

probably_damaging(0.999)

TCGA-CA-6716-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Chemotherapy

oxaliplatin

LIN28A

insertion

Nonsense_Mutation

novel

c.569_570insGTACAAAG

p.Tyr190Ter

p.Y190*

Q9H9Z2

protein_coding

TCGA-AM-5820-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Unknown

LIN28A

SNV

Missense_Mutation

c.387N>A

p.Met129Ile

p.M129I

Q9H9Z2

protein_coding

tolerated(0.19)

benign(0)

TCGA-AJ-A3EJ-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Unknown

LIN28A

SNV

Missense_Mutation

c.11T>C

p.Val4Ala

p.V4A

Q9H9Z2

protein_coding

deleterious_low_confidence(0)

probably_damaging(0.935)

TCGA-AP-A051-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

LIN28A

SNV

Missense_Mutation

novel

c.157N>C

p.Phe53Leu

p.F53L

Q9H9Z2

protein_coding

tolerated(0.1)

probably_damaging(0.981)

TCGA-AP-A059-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

LIN28A

SNV

Missense_Mutation

c.148C>T

p.Arg50Cys

p.R50C

Q9H9Z2

protein_coding

tolerated(0.1)

probably_damaging(0.999)

TCGA-AX-A2HC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

paclitaxel

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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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