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Research article
Yi-long Wu
Corresponding Author
ORCiD: https://orcid.org/0000-0002-3611-0258
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This work is licensed under a CC BY 4.0 License. Read Full License
Background: There were scarcely germline variants of familial lung cancer (LC) identified. We conducted an study with whole-exome sequencing of pedigrees with familial lung cancer to analyze the potential genetic susceptibility.
Methods: Probands with the highest hereditary background were identified by our large-scale epidemiological study and five ones were enrolled as a learning set. The germline SNPs (single-nucleotide polymorphisms) of other five similar probands, four healthy individuals in the formerly pedigrees and three patients with sporadic LC were used as a validation set, controlled by three healthy individuals without family history of any cancer. The network of mutated genes was generated using STRING-DB and visualized using Cytoscape.
Results: Specific and shared somatic mutations and germline SNPs were not the shared cause of familial lung cancer. However, individual germline SNPs showed distinct protein-protein interaction network patterns in probands versus healthy individuals and patients with sporadic lung cancer. SNP-containing genes were enriched in the PI3K/AKT pathway. These results were validated in the validation set. Furthermore, patients with familial lung cancer were distinguished by many germline variations in the PI3K/AKT pathway by a simple SVM classification method. It is worth emphasizing that one person with many germline variations in the PI3K/AKT pathway developed lung cancer during follow-up.
Conclusions: The phenomenon that the enrichments of germline SNPs in the PI3K/AKT pathway might be a major predictor of familial susceptibility to lung cancer.
Keywords
PI3K/AKT pathway, familial lung cancer, germline variation networks, whole-exome sequencing
Figure 1
Figure 2
Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryMethods.docx
Supplementary Methods：Support vector machine (SVM) classification
- SupplementaryFigS1.png
Supplementary Figure S1: Protein-protein interaction (PPI) network constructed using the shared germline mutated genes of the five LC probands. Disconnected genes were removed from the graph.
- SupplementaryFigS2.tif
Supplementary Figure S2: Bioinformatic workflow of next-generation sequencing data processing. FET = Fisher exact test.
- SupplementaryTableS1.docx
Supplementary Table S1: The questionnaire of the living environment
- SupplementaryTableS2.docx
Supplementary Table S2: The demographic and histologic of probands
- SupplementaryTableS3.docx
Supplementary Table S3: Summary of sequencing reads and mapping of the reads
- SupplementaryTableS4.xls
Supplementary Table S4: Somatic mutations of probands
- SupplementaryTableS5.xls
Supplementary Table S5: Shared germline mutations of probands
- SupplementaryTableS6.xlsx
Supplementary Table S6: Top 10 KEGG pathways of the non-synonymous mutated genes of the individuals
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CURRENT STATUS: Published
View the published article at BMC Cancer.
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Posted 22 Oct, 2020
No community comments so far
Submission checks complete
On 14 Oct, 2020
Editorial decision: Accept
On 13 Oct, 2020
No comments provided
Editorial decision: Minor revision
On 06 Oct, 2020
Review #1 received
Received 01 Oct, 2020
Review #2 received
Received 19 Sep, 2020
Reviewer #2 agreed
On 16 Sep, 2020
Reviewers invited
Invitations sent on 09 Sep, 2020
Reviewer #1 agreed
On 09 Sep, 2020
Editor assigned
On 12 Aug, 2020
Submission checks complete
On 11 Aug, 2020
Editor invited
On 11 Aug, 2020
No comments provided
Editorial decision: Major revision
On 13 Jul, 2020
Review #2 received
Received 12 Jul, 2020
Reviewer #4 agreed
On 24 Jun, 2020
Reviewer #2 agreed
On 22 Jun, 2020
Reviewer #3 agreed
On 22 Jun, 2020
Review #1 received
Received 26 Apr, 2020
Reviewer #1 agreed
On 22 Apr, 2020
Editor assigned
On 27 Mar, 2020
Reviewers invited
Invitations sent on 27 Mar, 2020
Submission checks complete
On 24 Mar, 2020
Editor invited
On 24 Mar, 2020
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
See the published version of this preprint at BMC Cancer.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Yi-long Wu
Corresponding Author
ORCiD: https://orcid.org/0000-0002-3611-0258
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Cancer.
Version 3
Posted 22 Oct, 2020
No community comments so far
Submission checks complete
On 14 Oct, 2020
Editorial decision: Accept
On 13 Oct, 2020
No comments provided
Editorial decision: Minor revision
On 06 Oct, 2020
Review #1 received
Received 01 Oct, 2020
Review #2 received
Received 19 Sep, 2020
Reviewer #2 agreed
On 16 Sep, 2020
Reviewers invited
Invitations sent on 09 Sep, 2020
Reviewer #1 agreed
On 09 Sep, 2020
Editor assigned
On 12 Aug, 2020
Submission checks complete
On 11 Aug, 2020
Editor invited
On 11 Aug, 2020
No comments provided
Editorial decision: Major revision
On 13 Jul, 2020
Review #2 received
Received 12 Jul, 2020
Reviewer #4 agreed
On 24 Jun, 2020
Reviewer #2 agreed
On 22 Jun, 2020
Reviewer #3 agreed
On 22 Jun, 2020
Review #1 received
Received 26 Apr, 2020
Reviewer #1 agreed
On 22 Apr, 2020
Editor assigned
On 27 Mar, 2020
Reviewers invited
Invitations sent on 27 Mar, 2020
Submission checks complete
On 24 Mar, 2020
Editor invited
On 24 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Cancer.
Background: There were scarcely germline variants of familial lung cancer (LC) identified. We conducted an study with whole-exome sequencing of pedigrees with familial lung cancer to analyze the potential genetic susceptibility.
Methods: Probands with the highest hereditary background were identified by our large-scale epidemiological study and five ones were enrolled as a learning set. The germline SNPs (single-nucleotide polymorphisms) of other five similar probands, four healthy individuals in the formerly pedigrees and three patients with sporadic LC were used as a validation set, controlled by three healthy individuals without family history of any cancer. The network of mutated genes was generated using STRING-DB and visualized using Cytoscape.
Results: Specific and shared somatic mutations and germline SNPs were not the shared cause of familial lung cancer. However, individual germline SNPs showed distinct protein-protein interaction network patterns in probands versus healthy individuals and patients with sporadic lung cancer. SNP-containing genes were enriched in the PI3K/AKT pathway. These results were validated in the validation set. Furthermore, patients with familial lung cancer were distinguished by many germline variations in the PI3K/AKT pathway by a simple SVM classification method. It is worth emphasizing that one person with many germline variations in the PI3K/AKT pathway developed lung cancer during follow-up.
Conclusions: The phenomenon that the enrichments of germline SNPs in the PI3K/AKT pathway might be a major predictor of familial susceptibility to lung cancer.
Figure 1
Figure 2
Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryMethods.docx
Supplementary Methods：Support vector machine (SVM) classification
- SupplementaryFigS1.png
Supplementary Figure S1: Protein-protein interaction (PPI) network constructed using the shared germline mutated genes of the five LC probands. Disconnected genes were removed from the graph.
- SupplementaryFigS2.tif
Supplementary Figure S2: Bioinformatic workflow of next-generation sequencing data processing. FET = Fisher exact test.
- SupplementaryTableS1.docx
Supplementary Table S1: The questionnaire of the living environment
- SupplementaryTableS2.docx
Supplementary Table S2: The demographic and histologic of probands
- SupplementaryTableS3.docx
Supplementary Table S3: Summary of sequencing reads and mapping of the reads
- SupplementaryTableS4.xls
Supplementary Table S4: Somatic mutations of probands
- SupplementaryTableS5.xls
Supplementary Table S5: Shared germline mutations of probands
- SupplementaryTableS6.xlsx
Supplementary Table S6: Top 10 KEGG pathways of the non-synonymous mutated genes of the individuals
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