Cancer Management and Research (Nov 2020)

Comprehensive Characterization of Stage IIIA Non-Small Cell Lung Carcinoma

  • Singh N,
  • Mishra A,
  • Sahu DK,
  • Jain M,
  • Shyam H,
  • Tripathi RK,
  • Shankar P,
  • Kumar A,
  • Alam N,
  • Jaiswal R,
  • Kumar S

Journal volume & issue
Vol. Volume 12
pp. 11973 – 11988

Abstract

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Neetu Singh,1,* Archana Mishra,2,* Dinesh Kumar Sahu,1,* Mayank Jain,1,* Hari Shyam,1,* Ratnesh Kumar Tripathi,1 Pratap Shankar,1 Anil Kumar,1 Nawazish Alam,1 Riddhi Jaiswal,3 Shailendra Kumar2 1Department of Centre for Advanced Research, King George’s Medical University, Lucknow, 226003, India; 2Department of Surgery, King George’s Medical University, Lucknow 226003, India; 3Department of Pathology, King George’s Medical University, Lucknow 226003, India*These authors contributed equally to this workCorrespondence: Neetu SinghDepartment of Centre for Advanced Research, King George’s Medical University, Lucknow 226003, IndiaTel +91-9984801444Fax +91-522-2257439Email [email protected] KumarDepartment of Surgery, King George’s Medical University, Lucknow 226 003, IndiaTel +91-8707001450Fax +91-522-2257439Email [email protected]: Heterogeneity of non-small cell lung carcinoma (NSCLC) among patients is currently not well studied. Pathologic markers and staging systems have not been a precise predictor of the prognosis of an individual patient. Hence, we hypothesize to develop a transcript-based signature to categorize stage IIIA-NSCLC in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), plus identify markers that could indicate the prognosis of the disease.Methods: Human Transcriptome Array 2.0 (HTA) and NanoString nCounter® platform were used for high-throughput gene-expression profiling. Initially, we profiled stage IIIA-NSCLC through HTA and validated through NanoString. Additionally, two metastatic markers SPP1 and CDH2 were validated in 47 NSCLC stage IIIA samples through real-time PCR.Results: We observed distinct gene clusters in LUAD and LUSC with down-regulation of six genes and up-regulation of 57 genes through HTA. Ninety-six transcripts were randomly selected after analyzing HTA data and validated on the NanoString platform. We found 40 differentially expressed transcripts that categorized NSCLC into LUAD and LUSC. SPP1 is significantly overexpressed (4.311± 1.27 fold in LUAD and 13.41± 3.82 fold in LUSC compared to control), and the CDH2 transcript was significantly overexpressed (11.53 ± 4.027-fold compared to control) only in LUSC.Discussion: These markers enable us to categorize stage IIIA NSCLC into LUAD and LUSC plus these markers may be helpful to understand the pathophysiology of NSCLC. However, more data required to make these findings useful in general clinical practice.Keywords: non-small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, human transcriptome array, NanoString

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