Singh Neetu, Mishra Archana, Sahu Dinesh Kumar, Jain Mayank, Shyam Hari, Tripathi Ratnesh Kumar, Shankar Pratap, Kumar Anil, Alam Nawazish, Jaiswal Riddhi, Kumar Shailendra
Department of Centre for Advanced Research, King George's Medical University, Lucknow, 226003, India.
Department of Surgery, King George's Medical University, Lucknow 226003, India.
Cancer Manag Res. 2020 Nov 20;12:11973-11988. doi: 10.2147/CMAR.S279974. eCollection 2020.
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.
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 and were validated in 47 NSCLC stage IIIA samples through real-time PCR.
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. is significantly overexpressed (4.311±1.27 fold in LUAD and 13.41±3.82 fold in LUSC compared to control), and the transcript was significantly overexpressed (11.53 ± 4.027-fold compared to control) only in LUSC.
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.
目前对非小细胞肺癌（NSCLC）患者之间的异质性研究不足。病理标志物和分期系统并非个体患者预后的精确预测指标。因此，我们假设开发一种基于转录本的特征，用于对肺腺癌（LUAD）和肺鳞状细胞癌（LUSC）中的IIIA期NSCLC进行分类，并识别可指示疾病预后的标志物。
使用人类转录组阵列2.0（HTA）和NanoString nCounter®平台进行高通量基因表达谱分析。最初，我们通过HTA对IIIA期NSCLC进行分析，并通过NanoString进行验证。此外，通过实时PCR在47例IIIA期NSCLC样本中验证了两种转移标志物。
通过HTA，我们在LUAD和LUSC中观察到不同的基因簇，六个基因下调，57个基因上调。在分析HTA数据后随机选择96个转录本，并在NanoString平台上进行验证。我们发现40个差异表达的转录本可将NSCLC分为LUAD和LUSC。 显著过表达（与对照相比，LUAD中为4.311±1.27倍，LUSC中为13.41±3.82倍），并且 转录本仅在LUSC中显著过表达（与对照相比为11.53±4.027倍）。
这些标志物使我们能够将IIIA期NSCLC分为LUAD和LUSC，此外这些标志物可能有助于理解NSCLC的病理生理学。然而，需要更多数据才能使这些发现应用于一般临床实践。
