The prognostic value of whole blood SOX2, NANOG and OCT4 mRNA expression in advanced small-cell lung cancer

Abstract

BackgroundThe data on expression and clinical impact of cancer stem cell markers SOX2, NANOG and OCT4 in lung cancer is still lacking. The aim of our study was to compare SOX2, NANOG and OCT4 mRNA expression levels in whole blood between advanced small-cell lung cancer (SCLC) patients and healthy controls, and to correlate mRNA expression with progression-free survival (PFS) after first-line chemotherapy and overall survival (OS) in advanced SCLC patients.Patients and methods50 advanced SCLC patients treated with standard chemotherapy and followed at University Clinic Golnik, Slovenia, between 2009 and 2013 were prospectively included. SOX2, NANOG and OCT4 mRNA expression levels were determined using TaqMan qPCR in whole blood collected prior to chemotherapy. Whole blood of 34 matched healthy individuals with no cancerous disease was also tested.ResultsSOX2 mRNA expression was significantly higher in whole blood of SCLC patients compared to healthy controls (p = 0.006). Significant correlation between SOX2 mRNA expression levels and the number of distant metastatic sites was established (p = 0.027). In survival analysis, patients with high SOX2 expression had shorter OS (p = 0.017) and PFS (p = 0.046). In multivariate Cox analysis, an independent value of high SOX2 expression for shorter OS (p = 0.002), but not PFS was confirmed. No significant differences were observed for NANOG or OCT4 expression levels when comparing SCLC patients and healthy controls neither when analysing survival outcomes in SCLC patients.ConclusionsSOX2 mRNA expression in whole blood might be a promising non-invasive marker for molecular screening of SCLC and important prognostic marker in advanced chemotherapy-treated SCLC patients, altogether indicating important role of cancer stem-like cell (CSC) regulators in cancer spread. Further evaluation of SOX2 as a possible screening/prognostic marker and a therapeutic target of SCLC is warranted.

Docetaxel promotes cell apoptosis and decreases SOX2 expression in CD133‑expressing hepatocellular carcinoma stem cells by suppressing the PI3K/AKT signaling pathway

“…In a review study, the role of SOX2 as a prognostic marker, indicator of metastasis, or biomarker in cancer pathogenesis was highlighted (35). Recently, numerous studies have provided evidence that SOX2 mRNA expression was significantly higher in patients with small-cell lung (36), gastric (37), breast (38), cervical (39) and ovarian epithelial cancer (40) compared to the healthy controls. A high level of SOX2 expression was revealed to be correlated with metastasis and a low survival rate in HCC (41).…”

Isolation and Identification of Cancer Stem-Like Cells in Adenocarcinoma and Squamous Cell Carcinoma of the Lung: A Pilot Study

“…An enrichment of CSCs in the ALDH high population was also described in NSCLC patients and cell lines (52). In addition, several key regulators have been described as essential for the maintenance of a progenitor cell state under both normal and cancerous conditions (e.g., SOX2 and the homeobox protein NANOG) (53,54). Following these investigations, the aim of the present study was to identify cancer stem-like cells in primary human lung cancer cells obtained from surgical specimens and to assess the differences and similarities between adenocarcinoma (ADENO) and squamous (SQUAMO) cell carcinoma using a combination of ALDH and CD44.…”

The clinicopathological and prognostic value of the pretreatment neutrophil-to-lymphocyte ratio in small cell lung cancer: A meta-analysis

“…Thus, the identification of novel biomarkers for predicting prognosis is essential for improving long-term outcomes. Although some new biomarkers have been shown to be independent prognostic factors for SCLC [3,4], most of these biomarkers are expensive and time-consuming to detect. Therefore, identification of inexpensive and simple biomarkers for SCLC may have important clinical implications.…”