High SOX2 Levels Predict Better Outcome in Non-Small Cell Lung Carcinomas

Velcheti, Vamsidhar; Schalper, Kurt A.; Yao, Xiaopan; Cheng, Hao; Kocoglu, Mehmet H.; Dhodapkar, Kavita M.; Deng, Yanhong; Gettinger, Scott; Rimm, David L.

doi:10.1371/journal.pone.0061427

Cited by 43 publications

(43 citation statements)

References 24 publications

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“…The results of the present study showed that the expression of SOX2 in NSCLC tissues was higher than that in the para-carcinoma tissues and a high SOX2 expression mainly occurred in lung squamous cell carcinoma cells. The study results were consistent with those of European and Japanese investigators (11,13). …”

Section: Discussionsupporting

confidence: 92%

Expression and significance of SOX2 in non-small cell lung carcinoma

Jin

Shi

et al. 2016

Oncology Letters

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The aim of the present study was to examine the expression and clinical significance of SOX2 in non-small cell lung carcinoma (NSCLC). Immunohistochemistry was used to detect the expression level of SOX2 in 127 cases of NSCLC. The Chi-square test was used to analyze the association of SOX2 expression and clinicopathological factors in NSCLC and para-carcinoma tissues (2.5%). The Kaplan-Meier method was applied to plot the survival curve, and the log-rank test and COX multiple regression model were applied to determine survival. SOX2 showed a high expression in 35.4% NSCLC tissues, which was significantly higher than that of the para-carcinoma tissues. The expression level of SOX2 was not associated with gender, age, smoking history or TNM stage (P>0.05), but was significantly associated with the pathological type of carcinoma. The high expression rate of SOX2 in lung squamous cell carcinoma was 50% (25/50) and in lung adenocarcinoma was 20.3% (12/59). Survival analysis indicated that the prognosis of patients with a high SOX2 expression was significantly better than those with a low SOX2 expression. The COX multiple regression analysis revealed that the expression level of SOX2 was an independent prognostic factor of patients with NSCLC (P<0.001). In conclusion, the expression of SOX2 in NSCLC tissues was upregulated, which was associated with the pathological type of carcinoma, while a high SOX2 expression mainly occurred in lung squamous cell carcinoma.

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Section: Discussionsupporting

confidence: 92%

Expression and significance of SOX2 in non-small cell lung carcinoma

Jin

Shi

et al. 2016

Oncology Letters

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“…16,53,55,57,68 For lung cancer, the proposed mechanism involves squamous maturation and thus improved response to chemotherapy. 69,70 The current study is the first report linking Sox2 amplification to improved outcome in serous ovarian cancer. In this model, we proposed a novel p53-dependent mechanism involving Sox2, Nanog, and Oct4 to explain the improved outcome noted in serous ovarian cancer.…”

Section: Discussionmentioning

confidence: 78%

Sox2 Gene Amplification Significantly Impacts Overall Survival in Serous Epithelial Ovarian Cancer

et al. 2015

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Epithelial ovarian cancer (EOC) is the deadliest gynecologic cancer. Recently, the existence of ovarian cancer stem cells has been reported. Sox2, Nanog and Oct4 are key markers of ''stemness''. The objective of this study was to determine whether Sox2, Nanog, and Oct4 are associated with EOC and poor outcome. The expression of these markers was assessed by immunofluorescence staining and real-time RT-PCR in human EOC cell lines MDAH-2774 and SKOV-3, while the cancer genome atlas (TCGA) dataset was analyzed for associations with survival. Sox2, Nanog and Oct4 (POU5F1) were all detected by immunofluorescence staining and these results were confirmed by real-time RT-PCR. The TCGA dataset revealed a 26%, 9%, and 6% amplification of Sox2, Nanog and POU5F1, respectively. Additionally, K-M survival analyses showed a significant median overall survival difference (41 versus 48.3 months, P ¼ .01) for Sox2 amplification, but not for Nanog (44.1 versus 36.2 months, P > .05) and POU5F1 (43.5 versus 45.0 months, P > .05). Our results suggest that Sox2 gene amplification significantly influences overall survival.

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“…Of which, 19 articles reported SOX2 DNA amplification and/or protein expression [13–16, 37–51], six articles reported Nestin protein expression, and none reported Nestin DNA amplification [21, 52–56]. In addition, Velcheti et al [46] and Iijima et al [50] reported two independent cohorts, respectively, and each cohort was considered as independent study in the meta-analysis. The included studies were published from 2010 to 2015 and the sample size ranged from 33 to 758.…”

Section: Resultsmentioning

confidence: 99%

Association of SOX2 and Nestin DNA amplification and protein expression with clinical features and overall survival in non-small cell lung cancer: A systematic review and meta-analysis

Liu

Zhang³

et al. 2016

Oncotarget

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Up to now, the prognosis of non-small cell lung cancer (NSCLC) is poor. With progress of cancer biology, a number of genes have been investigated for predicting prognosis of NSCLC, such as cancer stem cell markers SRY (sex determining region Y)-box 2 (SOX2) and Nestin. Recently, a series of studies have been performed to examine the associations of SOX2 and Nestin with clinical parameters and prognosis in NSCLC, however, the results were not consistent. In the present study, we conducted a systematic review and meta-analysis to summarize the associations. Four English databases (PubMed, ISI web of science, Embase, and Ovid) were used to search the relevant studies with the last date of November 10, 2015. The pooling analyses were stratified by DNA amplification and protein expression. The pooling ORs or HRs were used to assess the strength of the associations. Finally, we included 19 articles for SOX2 and six articles for Nestin according to the inclusion and exclusion criteria. The pooling analyses revealed that there were significant associations between SOX2 DNA amplification and clinical features of NSCLC, gender, smoking status, squamous cell cancer (SCC) histology, and differentiations. And significant associations were also identified between SOX2 protein expression and clinical parameters, smoking status and SCC histology. For Nestin, its protein expression was correlated with lymph node metastasis and stage. Simultaneously, we found that high/positive SOX2 alterations, either DNA amplification or protein expression, were favorable for overall survival (OS) in NSCLC. On the contrary, high/positive Nestin protein expression was poor for OS.

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High SOX2 Levels Predict Better Outcome in Non-Small Cell Lung Carcinomas

Cited by 43 publications

References 24 publications

Expression and significance of SOX2 in non-small cell lung carcinoma

Expression and significance of SOX2 in non-small cell lung carcinoma

Sox2 Gene Amplification Significantly Impacts Overall Survival in Serous Epithelial Ovarian Cancer

Association of SOX2 and Nestin DNA amplification and protein expression with clinical features and overall survival in non-small cell lung cancer: A systematic review and meta-analysis

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