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: CIT

Gene summary for CIT

Gene summary.

Gene information	Species	Human
	Gene symbol	CIT
	Gene ID	11113
	Gene name	citron rho-interacting serine/threonine kinase
	Gene Alias	CITK
	Cytomap	12q24.23
	Gene Type	protein-coding
	GO ID	GO:0000278
	UniProtAcc	O14578

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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
11113	CIT	TD9	Human	Lung	IAC	1.02e-02	5.71e-01	0.088
11113	CIT	RNA-P6T1-P6T1-1	Human	Lung	MIAC	6.67e-04	9.05e-01	-0.0238

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma

∗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:001821021	Lung	MIAC	peptidyl-threonine modification	16/967	125/18723	7.11e-04	1.61e-02	16
GO:0051302	Lung	MIAC	regulation of cell division	20/967	177/18723	8.41e-04	1.83e-02	20
GO:00353292	Lung	MIAC	hippo signaling	8/967	40/18723	8.64e-04	1.86e-02	8
GO:009006811	Lung	MIAC	positive regulation of cell cycle process	23/967	236/18723	2.65e-03	3.71e-02	23
GO:004578712	Lung	MIAC	positive regulation of cell cycle	28/967	313/18723	3.42e-03	4.43e-02	28
GO:000091012	Lung	MIAC	cytokinesis	18/967	173/18723	3.71e-03	4.60e-02	18
GO:007099723	Lung	MIAC	neuron death	31/967	361/18723	3.97e-03	4.79e-02	31
GO:007048219	Oral cavity	OSCC	response to oxygen levels	200/7305	347/18723	1.17e-12	5.13e-11	200
GO:000756818	Oral cavity	OSCC	aging	194/7305	339/18723	6.18e-12	2.33e-10	194
GO:000170116	Oral cavity	OSCC	in utero embryonic development	207/7305	367/18723	7.92e-12	2.95e-10	207
GO:003009920	Oral cavity	OSCC	myeloid cell differentiation	213/7305	381/18723	1.24e-11	4.42e-10	213
GO:000166619	Oral cavity	OSCC	response to hypoxia	177/7305	307/18723	2.21e-11	7.50e-10	177
GO:003629319	Oral cavity	OSCC	response to decreased oxygen levels	182/7305	322/18723	1.14e-10	3.41e-09	182
GO:000226220	Oral cavity	OSCC	myeloid cell homeostasis	98/7305	157/18723	2.29e-09	5.34e-08	98
GO:00457879	Oral cavity	OSCC	positive regulation of cell cycle	173/7305	313/18723	3.28e-09	7.44e-08	173
GO:003052218	Oral cavity	OSCC	intracellular receptor signaling pathway	149/7305	265/18723	8.69e-09	1.81e-07	149
GO:004887220	Oral cavity	OSCC	homeostasis of number of cells	152/7305	272/18723	1.08e-08	2.23e-07	152
GO:004873220	Oral cavity	OSCC	gland development	226/7305	436/18723	2.78e-08	5.39e-07	226
GO:003410120	Oral cavity	OSCC	erythrocyte homeostasis	81/7305	129/18723	3.75e-08	7.06e-07	81
GO:004578520	Oral cavity	OSCC	positive regulation of cell adhesion	225/7305	437/18723	6.06e-08	1.09e-06	225

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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

CIT

SNV

Missense_Mutation

rs779515686

c.4130N>T

p.Pro1377Leu

p.P1377L

O14578

protein_coding

deleterious(0)

benign(0.248)

TCGA-A2-A0EW-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

adriamycin

CIT

SNV

Missense_Mutation

c.5132C>T

p.Ser1711Phe

p.S1711F

O14578

protein_coding

deleterious(0)

probably_damaging(0.972)

TCGA-A2-A0SV-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Other, specify in notesBisphosphonate therapy

zometa

CIT

SNV

Missense_Mutation

novel

c.2482N>A

p.Glu828Lys

p.E828K

O14578

protein_coding

deleterious(0.04)

possibly_damaging(0.628)

TCGA-A2-A25C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

taxotere

CIT

SNV

Missense_Mutation

c.3097G>T

p.Val1033Leu

p.V1033L

O14578

protein_coding

tolerated(0.08)

probably_damaging(0.978)

TCGA-A8-A076-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

CIT

SNV

Missense_Mutation

rs747447396

c.2839C>T

p.Arg947Cys

p.R947C

O14578

protein_coding

deleterious(0.02)

possibly_damaging(0.446)

TCGA-A8-A09X-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Unknown

CIT

SNV

Missense_Mutation

rs747447396

c.2839N>T

p.Arg947Cys

p.R947C

O14578

protein_coding

deleterious(0.02)

possibly_damaging(0.446)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CIT

SNV

Missense_Mutation

c.242N>T

p.Ser81Phe

p.S81F

O14578

protein_coding

deleterious(0.02)

benign(0.17)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CIT

SNV

Missense_Mutation

novel

c.637N>T

p.His213Tyr

p.H213Y

O14578

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AC-A5XS-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

femara

CIT

SNV

Missense_Mutation

rs368981957

c.5590N>A

p.Asp1864Asn

p.D1864N

O14578

protein_coding

deleterious(0)

probably_damaging(0.964)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

CIT

SNV

Missense_Mutation

novel

c.1771N>A

p.Glu591Lys

p.E591K

O14578

protein_coding

tolerated(0.31)

benign(0.019)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=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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