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: FLOT1

Gene summary for FLOT1

Gene summary.

Gene information	Species	Human
	Gene symbol	FLOT1
	Gene ID	10211
	Gene name	flotillin 1
	Gene Alias	FLOT1
	Cytomap	6p21.33
	Gene Type	protein-coding
	GO ID	GO:0000768
	UniProtAcc	O75955

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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
10211	FLOT1	HTA11_2487_2000001011	Human	Colorectum	SER	1.65e-03	4.54e-01	-0.1808
10211	FLOT1	HTA11_347_2000001011	Human	Colorectum	AD	5.85e-10	4.86e-01	-0.1954
10211	FLOT1	HTA11_866_2000001011	Human	Colorectum	AD	1.26e-05	4.59e-01	-0.1001
10211	FLOT1	HTA11_1391_2000001011	Human	Colorectum	AD	1.39e-08	6.02e-01	-0.059
10211	FLOT1	HTA11_866_3004761011	Human	Colorectum	AD	1.34e-11	5.55e-01	0.096
10211	FLOT1	HTA11_10623_2000001011	Human	Colorectum	AD	1.20e-02	5.27e-01	-0.0177
10211	FLOT1	HTA11_7696_3000711011	Human	Colorectum	AD	1.17e-03	4.09e-01	0.0674
10211	FLOT1	HTA11_99999971662_82457	Human	Colorectum	MSS	3.05e-09	7.12e-01	0.3859
10211	FLOT1	A015-C-203	Human	Colorectum	FAP	8.15e-09	-1.60e-01	-0.1294
10211	FLOT1	A002-C-201	Human	Colorectum	FAP	2.48e-02	-2.50e-02	0.0324
10211	FLOT1	A001-C-108	Human	Colorectum	FAP	1.81e-04	-1.01e-01	-0.0272
10211	FLOT1	A002-C-205	Human	Colorectum	FAP	8.95e-06	-1.47e-01	-0.1236
10211	FLOT1	A015-C-006	Human	Colorectum	FAP	1.67e-04	-1.10e-01	-0.0994
10211	FLOT1	A002-C-114	Human	Colorectum	FAP	1.36e-04	-1.06e-01	-0.1561
10211	FLOT1	A015-C-104	Human	Colorectum	FAP	2.36e-09	-9.99e-02	-0.1899
10211	FLOT1	A002-C-016	Human	Colorectum	FAP	5.64e-06	-1.51e-01	0.0521
10211	FLOT1	A015-C-002	Human	Colorectum	FAP	2.06e-02	-1.64e-01	-0.0763
10211	FLOT1	A002-C-116	Human	Colorectum	FAP	3.57e-12	-1.94e-01	-0.0452
10211	FLOT1	A014-C-008	Human	Colorectum	FAP	2.46e-03	-1.19e-01	-0.191
10211	FLOT1	A018-E-020	Human	Colorectum	FAP	3.24e-05	-1.11e-01	-0.2034

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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
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
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:005109015	Oral cavity	LP	regulation of DNA-binding transcription factor activity	147/4623	440/18723	2.00e-05	3.35e-04	147
GO:0051099110	Oral cavity	LP	positive regulation of binding	67/4623	173/18723	2.86e-05	4.51e-04	67
GO:004311216	Oral cavity	LP	receptor metabolic process	64/4623	166/18723	5.00e-05	7.02e-04	64
GO:000689817	Oral cavity	LP	receptor-mediated endocytosis	87/4623	244/18723	7.83e-05	1.02e-03	87
GO:003209215	Oral cavity	LP	positive regulation of protein binding	35/4623	85/18723	5.94e-04	5.44e-03	35
GO:004409113	Oral cavity	LP	membrane biogenesis	25/4623	55/18723	6.27e-04	5.71e-03	25
GO:007170913	Oral cavity	LP	membrane assembly	23/4623	50/18723	8.33e-04	7.27e-03	23
GO:000726515	Oral cavity	LP	Ras protein signal transduction	109/4623	337/18723	8.44e-04	7.36e-03	109
GO:00017654	Oral cavity	LP	membrane raft assembly	8/4623	11/18723	1.08e-03	9.01e-03	8
GO:005109114	Oral cavity	LP	positive regulation of DNA-binding transcription factor activity	86/4623	260/18723	1.35e-03	1.08e-02	86
GO:0045785110	Oral cavity	LP	positive regulation of cell adhesion	134/4623	437/18723	2.44e-03	1.74e-02	134
GO:003157914	Oral cavity	LP	membrane raft organization	13/4623	25/18723	2.98e-03	2.04e-02	13
GO:003248111	Oral cavity	LP	positive regulation of type I interferon production	24/4623	58/18723	3.78e-03	2.48e-02	24
GO:004580717	Oral cavity	LP	positive regulation of endocytosis	36/4623	100/18723	7.54e-03	4.16e-02	36
GO:00713591	Oral cavity	LP	cellular response to dsRNA	11/4623	22/18723	9.01e-03	4.83e-02	11
GO:000276413	Oral cavity	EOLP	immune response-regulating signaling pathway	108/2218	468/18723	4.04e-12	7.34e-10	108
GO:003164726	Oral cavity	EOLP	regulation of protein stability	75/2218	298/18723	1.22e-10	1.35e-08	75
GO:000640323	Oral cavity	EOLP	RNA localization	57/2218	201/18723	1.62e-10	1.68e-08	57
GO:003497624	Oral cavity	EOLP	response to endoplasmic reticulum stress	66/2218	256/18723	5.33e-10	4.31e-08	66
GO:004578526	Oral cavity	EOLP	positive regulation of cell adhesion	95/2218	437/18723	2.30e-09	1.47e-07	95

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa04910	Colorectum	MSS	Insulin signaling pathway	43/1875	137/8465	7.37e-03	2.84e-02	1.74e-02	43
hsa049101	Colorectum	MSS	Insulin signaling pathway	43/1875	137/8465	7.37e-03	2.84e-02	1.74e-02	43
hsa049102	Colorectum	FAP	Insulin signaling pathway	36/1404	137/8465	2.51e-03	1.18e-02	7.18e-03	36
hsa049103	Colorectum	FAP	Insulin signaling pathway	36/1404	137/8465	2.51e-03	1.18e-02	7.18e-03	36
hsa049109	Esophagus	ESCC	Insulin signaling pathway	89/4205	137/8465	1.97e-04	7.32e-04	3.75e-04	89
hsa0491014	Esophagus	ESCC	Insulin signaling pathway	89/4205	137/8465	1.97e-04	7.32e-04	3.75e-04	89
hsa0491021	Liver	Cirrhotic	Insulin signaling pathway	56/2530	137/8465	3.74e-03	1.50e-02	9.26e-03	56
hsa0491031	Liver	Cirrhotic	Insulin signaling pathway	56/2530	137/8465	3.74e-03	1.50e-02	9.26e-03	56
hsa0491041	Liver	HCC	Insulin signaling pathway	95/4020	137/8465	1.53e-07	1.97e-06	1.10e-06	95
hsa0491051	Liver	HCC	Insulin signaling pathway	95/4020	137/8465	1.53e-07	1.97e-06	1.10e-06	95
hsa049108	Oral cavity	OSCC	Insulin signaling pathway	83/3704	137/8465	4.83e-05	2.00e-04	1.02e-04	83
hsa0491013	Oral cavity	OSCC	Insulin signaling pathway	83/3704	137/8465	4.83e-05	2.00e-04	1.02e-04	83
hsa0491023	Oral cavity	EOLP	Insulin signaling pathway	33/1218	137/8465	1.61e-03	5.60e-03	3.30e-03	33
hsa0491033	Oral cavity	EOLP	Insulin signaling pathway	33/1218	137/8465	1.61e-03	5.60e-03	3.30e-03	33
hsa049107	Prostate	BPH	Insulin signaling pathway	43/1718	137/8465	1.34e-03	5.81e-03	3.60e-03	43
hsa0491012	Prostate	BPH	Insulin signaling pathway	43/1718	137/8465	1.34e-03	5.81e-03	3.60e-03	43
hsa0491022	Prostate	Tumor	Insulin signaling pathway	44/1791	137/8465	1.69e-03	7.10e-03	4.40e-03	44
hsa0491032	Prostate	Tumor	Insulin signaling pathway	44/1791	137/8465	1.69e-03	7.10e-03	4.40e-03	44

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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

FLOT1

SNV

Missense_Mutation

c.782N>A

p.Arg261Gln

p.R261Q

O75955

protein_coding

deleterious(0)

possibly_damaging(0.87)

TCGA-A8-A08S-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

anastrozole

FLOT1

insertion

Frame_Shift_Ins

novel

c.476_477insGTCAAGCACATGCAAATGTGGCATGACTTATTGGGAGCAGAAAC

p.Asp159GlufsTer61

p.D159Efs*61

O75955

protein_coding

TCGA-A2-A0CX-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

adriamycin

FLOT1

insertion

Nonsense_Mutation

novel

c.381_382insAATATATTTTACATAAGGTGTCTTTAAACAGAAACA

p.Phe127_Ser128insAsnIlePheTyrIleArgCysLeuTerThrGluThr

p.F127_S128insNIFYIRCL*TET

O75955

protein_coding

TCGA-A8-A06O-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

letrozole

FLOT1

insertion

Frame_Shift_Ins

novel

c.508_509insGCTGTGCCCGTGCAAAGGAG

p.Ala170GlyfsTer42

p.A170Gfs*42

O75955

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

FLOT1

SNV

Missense_Mutation

rs568759969

c.692G>A

p.Arg231Gln

p.R231Q

O75955

protein_coding

tolerated(0.16)

benign(0.007)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

FLOT1

SNV

Missense_Mutation

novel

c.1138C>A

p.Leu380Met

p.L380M

O75955

protein_coding

tolerated(1)

benign(0.007)

TCGA-VS-A9V0-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

FLOT1

SNV

Missense_Mutation

c.11N>T

p.Thr4Ile

p.T4I

O75955

protein_coding

tolerated(0.06)

benign(0.257)

TCGA-AA-3854-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

FLOT1

SNV

Missense_Mutation

c.83N>T

p.Arg28Leu

p.R28L

O75955

protein_coding

tolerated(0.16)

probably_damaging(0.964)

TCGA-AA-3989-01

Colorectum

colon adenocarcinoma

Male

>=65

III/IV

Unknown

FLOT1

SNV

Missense_Mutation

c.245N>A

p.Ala82Glu

p.A82E

O75955

protein_coding

tolerated(0.27)

possibly_damaging(0.544)

TCGA-AA-A010-01

Colorectum

colon adenocarcinoma

Female

<65

I/II

Chemotherapy

folinic

FLOT1

SNV

Missense_Mutation

rs201200201

c.1240N>A

p.Val414Met

p.V414M

O75955

protein_coding

deleterious(0)

probably_damaging(0.915)

TCGA-AD-6889-01

Colorectum

colon adenocarcinoma

Male

>=65

I/II

Chemotherapy

xeloda

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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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