MOLECULAR STRATIFICATION OF LUNG ADENOCARCINOMA USING GENE EXPRESSION

Nagaraju  Indugu; D W Pitta; G Venkata  Subbaiah; K Jagadeeswara  Reddy; C Damodar  Reddy; K Satyavelu  Reddy

doi:10.22270/ijmspr.v1i4.12

Authors

Nagaraju Indugu Department of Zoology, Division of Bioinformatics, S V University, Tirupati 517502, Andhra Pradesh, India
D W Pitta Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348.
G Venkata Subbaiah Department of Zoology, Division of Bioinformatics, S V University, Tirupati 517502, Andhra Pradesh, India
K Jagadeeswara Reddy Sugen Life Science Private Limited, Tirupati, India
C Damodar Reddy Sugen Life Science Private Limited, Tirupati, India
K Satyavelu Reddy Department of Zoology, Division of Bioinformatics, S V University, Tirupati 517502, Andhra Pradesh, India.

DOI:

https://doi.org/10.22270/ijmspr.v1i4.12

Keywords:

TCGA, Lung adenocarcinoma, Molecular stratification, RNA-seq

Abstract

Molecular stratification of tumors is essential for developing personalized therapies. Although patient stratification strategies have been successful; computational methods to accurately translate the gene-signature from high-throughput platform to a clinically adaptable low-dimensional platform are currently lacking. Here, we describe bioinformatics method for identification of biomarkers in lung adenocarcinoma using unsupervised clustering of TCGA (the Cancer Genome Altas Consortium) samples, based on gene-expression profiles, recaptured the three molecular subgroups but switched the subtype for 14% of the samples, resulting in significant (P = 0.000344) survival differences among the refined subgroups. Our results were able to define three subgroups of lung adennocarcinoma that differed not only in gene expression patterns, but also in clinical properties, including patient survival.

Author Biographies

Nagaraju Indugu, Department of Zoology, Division of Bioinformatics, S V University, Tirupati 517502, Andhra Pradesh, India

Department of Zoology, Division of Bioinformatics, S V University, Tirupati 517502, Andhra Pradesh, India

D W Pitta , Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348.

Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348.

G Venkata Subbaiah, Department of Zoology, Division of Bioinformatics, S V University, Tirupati 517502, Andhra Pradesh, India

Department of Zoology, Division of Bioinformatics, S V University, Tirupati 517502, Andhra Pradesh, India

K Jagadeeswara Reddy, Sugen Life Science Private Limited, Tirupati, India

Sugen Life Science Private Limited, Tirupati, India

C Damodar Reddy, Sugen Life Science Private Limited, Tirupati, India

Sugen Life Science Private Limited, Tirupati, India

K Satyavelu Reddy, Department of Zoology, Division of Bioinformatics, S V University, Tirupati 517502, Andhra Pradesh, India.

Department of Zoology, Division of Bioinformatics, S V University, Tirupati 517502, Andhra Pradesh, India.

References

Beer D G, Kardia S L, Huang C-C, Giordano T J, Levin A M, Misek D E and Thomas D G (2002), “Gene-Expression Profiles Predict Survival of Patients with Lung Adenocarcinoma”, Nature Medicine, Vol. 8, No. 8, pp. 816-824.

Bhattacharjee A, Richards W G, Staunton J, Li C, Monti S, Vasa P and Gillette M (2001), “Classification of Human Lung Carcinomas by mRNA Expression Profiling Reveals Distinct Adenocarcinoma Subclasses”, Proceedings of the National Academy of Sciences, Vol. 98, No. 24, pp. 13790-13795.

Eldridge L (2015), “Lung Adenocarcinoma Symptoms, Treatments, and Prognosis”, 35 from https://lungcancer.about.com/od/ t y p e s o f l u n g c a n c e r / a / L u n g - Adenocarcinoma.htm 4

Etzioni R, Urban N, Ramsey S, McIntosh M, Schwartz S, Reid B and Hartwell L (2003), “The Case for Early Detection”, Nature Reviews Cancer, Vol. 3, No. 4, pp. 243-252.

Fridman J S and Lowe S W (2003), “Control of Apoptosis by p53”, Oncogene, Vol. 22, No. 56, pp. 9030-9040.

Garber M E, Troyanskaya O G, Schluens K, Petersen S, Thaesler Z, Pacyna-Gengelbach M and Whyte R I (2001), “Diversity of Gene Expression in Adenocarcinoma of the Lung”, Proceedings of the National Academy of Sciences, Vol. 98, No. 24, pp. 13784-13789.

Hayes D F, Bast R C, Desch C E, Fritsche H, Kemeny N E, Jessup J M and Norton L (1996), “Tumor Marker Utility Grading System: A Framework to Evaluate Clinical Utility of Tumor Markers”, Journal of the National Cancer Institute, Vol. 88, No. 20, pp. 1456-1466.

Hayes D N, Monti S, Parmigiani G, Gilks C B, Naoki K, Bhattacharjee A and Meyerson M (2006), “Gene Expression Profiling Reveals Reproducible Human Lung Adenocarcinoma Subtypes in Multiple Independent Patient Cohorts”, Journal of Clinical Oncology, Vol. 24, No. 31, pp. 5079-5090.

Levy M A, Lovly C M and Pao W (2012), “Translating Genomic Information into Clinical Medicine: Lung Cancer as a Paradigm”, Genome Research, Vol. 22, No. 11, pp. 2101-2108.

Network C G A R (2014), “Comprehensive Molecular Profiling of Lung Adenocarcinoma”, Nature, Vol. 511, No. 7511, pp. 543-550.

Ritchie M E, Phipson B, Wu D, Hu Y, Law C W, Shi W and Smyth G K (2015), “Limma Powers Differential Expression Analyses for RNA-Sequencing and Microarray Studies”, Nucleic. Acids Res., gkv007.

Rousseeuw P J (1987), “Silhouettes: A Graphical Aid to the Interpretation and Validation of Cluster Analysis”, Journal of Computational and Applied Mathematics, Vol. 20, pp. 53-65.

Siegel R, Ma J, Zou Z and Jemal A (2014), “Cancer Statistics”, A Cancer Journal for Clinicians, Vol. 64, No. 1, pp. 9-29.

Takeuchi T, Tomida S, Yatabe Y, Kosaka T, Osada H, Yanagisawa K and Takahashi T (2006), “Expression Profile–Defined Classification of Lung Adenocarcinoma Shows Close Relationship with Underlying Major Genetic Changes and Clinicopathologic Behaviors”, Journal of Clinical Oncology, Vol. 24, No. 11, pp. 1679-1688.

Wilkerson M D, Yin X, Walter V, Zhao N, Cabanski C R, Hayward M C and Thorne L B (2012), “Differential Pathogenesis of Lung Adenocarcinoma Subtypes Involving Sequence Mutations, Copy Number, Chromosomal Instability, and Methylation”, PLoS ONE, Vol. 7, No. 5, p. e36530