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A proteogenomic profile of early lung adenocarcinomas by protein co-expression network and genomic alteration analysis.

ABSTRACT: The tumourigenesis of early lung adenocarcinomas, including adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and lepidic predominant invasive adenocarcinoma (LPA), remains unclear. This study aimed to capture disease-related molecular networks characterising each subtype and tumorigenesis by assessing 14 lung adenocarcinomas (AIS, five; MIA, five; LPA, four). Protein-protein interaction networks significant to the three subtypes were elucidated by weighted gene co-expression network analysis and pairwise G-statistics based analysis. Pathway enrichment analysis for AIS involved extracellular matrix proteoglycans and neutrophil degranulation pathway relating to tumour growth and angiogenesis. Whereas no direct networks were found for MIA, proteins significant to MIA were involved in oncogenic transformation, epithelial-mesenchymal transition, and detoxification in the lung. LPA was associated with pathways of HSF1-mediated heat shock response regulation, DNA damage repair, cell cycle regulation, and mitosis. Genomic alteration analysis suggested that LPA had both somatic mutations with loss of function and copy number gains more frequent than MIA. Oncogenic drivers were detected in both MIA and LPA, and also LPA had a higher degree of copy number loss than MIA. Our findings may help identifying potential therapeutic targets and developing therapeutic strategies to improve patient outcomes.

SUBMITTER: Nishimura T

PROVIDER: S-EPMC7423934 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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A proteogenomic profile of early lung adenocarcinomas by protein co-expression network and genomic alteration analysis.

Nishimura Toshihide T Nakamura Haruhiko H Tan Kien Thiam KT Zhuo De-Wei DW Fujii Kiyonaga K Koizumi Hirotaka H Naruki Saeko S Takagi Masayuki M Furuya Naoki N Kato Yasufumi Y Chen Shu-Jen SJ Kato Harubumi H Saji Hisashi H

Scientific reports 20200812 1

The tumourigenesis of early lung adenocarcinomas, including adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and lepidic predominant invasive adenocarcinoma (LPA), remains unclear. This study aimed to capture disease-related molecular networks characterising each subtype and tumorigenesis by assessing 14 lung adenocarcinomas (AIS, five; MIA, five; LPA, four). Protein-protein interaction networks significant to the three subtypes were elucidated by weighted gene co-expressio ...[more]

PMID: 32788598

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Project description:Lung adenocarcinoma (LUAD), the most prevalent form of non-small cell lung cancer (NSCLC), remains a leading cause of cancer-related death globally, including in India, with a 5-year survival rate below 10%. Despite these grim statistics, recent advances in the use of next-generation sequencing (NGS) for identifying genetic alterations and the emergence of targeted therapies have opened new possibilities for personalized treatment based on distinct molecular signatures. To understand the molecular pattern of NSCLC, a retrospective study was conducted with 53 Indian LUAD patient samples, using a targeted NGS panel of 46 cancer-relevant oncogenes to identify clinically relevant variants. Pathogenic or likely pathogenic variants were detected in 94% of the 53 cases. Non-synonymous mutations, rearrangements, copy number alterations, insertions, and deletions of functional relevance were observed in 31 out of 46 genes. The most frequently mutated genes included TP53 (52.8%) and EGFR (50.9%), followed by RET, PIK3CA and ERBB2; some patients had multiple alterations in the same gene. Gender-based enrichment analysis indicated that ALK and IDH2 alterations were more prevalent in females, while TP53 and PTEN were more common in males. No significant correlation was found between mutations and other clinicopathological attributes, such as age, stage, and subtype. A higher prevalence of EGFR, RET, PIK3CA, ERBB2 and ALK mutations were observed compared to previous LUAD genetic studies coupled with a lower frequency of KRAS mutations. Clinically actionable variants were annotated using OncoKB and categorized into the four therapeutic levels based on their clinical evidence. Seventy-nine percent of cases had at least one clinically actionable alteration. Most patients (39.6%) had the highest level of actionability (Level 1) wherein an FDA-approved drug is available specifically for the observed mutation in lung cancer patients. EGFR Exon19 in-frame deletions and EGFR L858R were the most frequent among targetable variants (20.7%). These findings emphasize the importance of a selective NGS panel in enabling personalized medicine approaches by identifying actionable molecular alterations and informing the choice of targeted therapy for more effective treatment options in Indian NSCLC patients.

Project description:Introduction: Breast cancer is one of the highest reasons of deaths for people in the world. The objective of current study is to analyze and visualize the trend of global scientific activities in the field of breast cancer during a period of 10 years through 2006-2015. Methods: The current study was performed by utilizing the scientometrics analysis and mapping the co-authorship and co-organization networks. The Web of Science Core Collection (WoS-CC)database was used to extract all papers indexed as a topic of breast cancer through 2006 to 2015. Research productivity was measured through analysis several parameters, including: the number and time course of publications, the journal and language of publications, the frequency and type of publications, as well as top 20 active sub-categories together with country contribution. The extracted data were transferred into the Excel charts and plotted as diagrams. The Science of Science (Sci2) and CiteSpace softwares were used as tools for mapping the co-authorship and co-organization networks of the published papers. Results: Analysis of data indicated that the number of publications in the field of breast cancer has linearly increased and correlated with the time-course of the study. The number of publication indexed in WoS-CC in 2015 was two times greater than that of 2006, which reached from 15 229 documents in 2006 to 30 667 documents in 2015. English Language accounted for 98% of total publications as the most dominant language. The vast majority of publications' type was in the form of original journal articles (64.7%). Based on Bradford scatterings law, the journal of "Cancer Research" was the most productive journal among the core journals, while the USA, China, and England were the most prolific countries in the field. The co-organization network indicated the dominant role of Harvard University in the field. Conclusion: The integrity of network indicated that scientists in the field of breast cancer working collaboratively to tackle the number one threat in women health.

Dataset Information

A proteogenomic profile of early lung adenocarcinomas by protein co-expression network and genomic alteration analysis.

Publications

A proteogenomic profile of early lung adenocarcinomas by protein co-expression network and genomic alteration analysis.

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