High circulating VEGF level predicts poor overall survival in lung cancer

At initial diagnosis, most patients with small-cell lung cancer (SCLC) present with metastatic disease with a high number of tumor cells (CTCs) circulating in the blood. We analyzed RNA transcripts specific for neuroendocrine and for epithelial cell lineages, and Notch pathway delta-like 3 ligand (DLL3), the actionable target of rovalpituzumab tesirine (Rova-T) in CTC samples. Peripheral blood samples from 48 SCLC patients were processed using the microfluidic Parsortix™ technology to enrich the CTCs. Blood samples from 26 healthy donors processed in the same way served as negative controls. The isolated cells were analyzed for the presence of above-mentioned transcripts using quantitative PCR. In total, 16/51 (31.4%) samples were CTC-positive as determined by the expression of epithelial cell adhesion molecule 1 (EpCAM), cytokeratin 19 (CK19), chromogranin A (CHGA), and/or synaptophysis (SYP). The epithelial cell lineage-specific EpCAM and/or CK19 gene expression was observed in 11 (21.6%) samples, and positivity was not associated with impaired survival. The neuroendocrine cell lineage-specific CHGA and/or SYP were positive in 13 (25.5%) samples, and positivity was associated with poor overall survival. DLL3 transcripts were observed in four (7.8%) SCLC blood samples and DLL3-positivity was similarly associated with poor overall survival (OS). CTCs in SCLC patients can be assessed using epithelial and neuroendocrine cell lineage markers at the molecular level. Thus, the implementation of liquid biopsy may improve the management of lung cancer patients, in terms of a faster diagnosis, patient stratification, and on-treatment therapy monitoring.

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High Expression of Truncated GLI3 is Associated with Poor Overall Survival in Patients with Non-Small-Cell Lung Cancer

Annals of Oncology ◽

10.1016/s0923-7534(20)32054-8 ◽

2012 ◽

Vol 23 ◽

pp. xi48

Author(s):

X.-Y. Bai ◽

J.-Y. Lin ◽

X.-C. Zhang ◽

Z. Xie ◽

H.-h. Yan ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

High Expression ◽

Small Cell Lung ◽

Poor Overall Survival

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Serum hepatocyte growth factor and interleukin-6 as prognostic markers for stage III non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.10542 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 10542-10542

Author(s):

Hideki Ujiie ◽

Mikio Tomida ◽

Hirohiko Akiyama ◽

Daisuke Okada ◽

Yuki Nakajima ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Growth Factor ◽

Hepatocyte Growth Factor ◽

Interleukin 6 ◽

Small Cell ◽

Stage Iii ◽

Small Cell Lung ◽

Poor Overall Survival ◽

Hepatocyte Growth

10542 Background: We surveyed prognostic biomarkers for resectable non-small cell lung cancer (NSCLC). Methods: We obtained preoperative serum from 109 patients admitted to our facility, and measured the levels of hepatocyte growth factor (HGF), interleukin-6 (IL-6), and nicotinamide N–methytransferase (NNMT) in the sera by the ELISA method. We also examined the clinical backgrounds of the patients. Results: The median HGF and IL-6 contents in sera from 109 patients were 860 pg/ml and 2.7 pg/ml, respectively. Analysis of survival curves indicated that HGF or IL-6 levels higher than the median were associated with poor overall survival (HGF, P = 0.019; IL-6, P = 0.002). On the other hand, carcinoembryonic antigen (CEA), a known tumor marker, and NNMT, which we found to be a candidate tumor marker, exhibited no correlation with the prognosis. The tumor status (pT factor) and stage were strong prognostic indicators (P < 0.001). In addition, we analyzed stage III lung cancer alone. Higher HGF or IL-6 levels were associated with poor overall survival (HGF, P = 0.016; IL-6, P = 0.013). Disease-free survival was also affected by these cytokine contents, but not statistically significantly. The prognosis of patients with adenocarcinomas (ADC) was better than that of patients with other histological types. However, the pT factor and nodal status (pN factor) were not associated with the survival of stage III patients. Conclusions: The levels of HGF and IL-6 in serum could be useful prognostic indicator of the survival of stage III NSCLC patients undergoing surgery and chemotherapy.

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Circulating tumor cell (CTC) as a significant prognostic factor in resected primary lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e23044 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e23044-e23044 ◽

Cited By ~ 1

Author(s):

Kazue Yoneda ◽

Masaki Hashimoto ◽

Teruhisa Takuwa ◽

Seiji Matsumoto ◽

Yoshitomo Okumura ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Multivariate Analysis ◽

Survival Rate ◽

Primary Lung Cancer ◽

Circulating Tumor Cell ◽

Small Cell ◽

Recurrence Free Survival ◽

Poor Overall Survival ◽

Free Survival

e23044 Background: Circulating tumor cell (CTC) is a potentially useful marker in early diagnosis and monitoring therapeutic effects for patients with malignant tumors, but clinical significance of CTC in primary lung cancer remains unclear. We previously showed that CTC was a useful surrogate marker of distant metastasis in primary lung cancer (Clin Cancer Res 2009). In this study, we evaluated the prognostic value among completely resected patients after long-term follow-up. Methods: A total of 94 patients (median age, 68 years; 30 females and 64 males) who underwent complete resection for primary lung cancer (4 with small cell and 90 with non-small cell) were prospectively evaluated. At the time of enrollment into the study, 7.5mL of peripheral blood was sampled from each patient, and an EpCAM-based detection system (CellSearch) was used for detection of CTC. CTC was detected in 16 patients (CTC-positive, 14.9%). Results: CTC-positivity was significantly associated with a poor recurrence-free survival (5-year recurrence-free survival rate, 40% versus 72%; p<0.01) (Table 1), which was confirmed by a multivariate analysis (hazard ratio, 2.57 [95% CI, 1.26-5.26]; P=0.010). CTC-positivity was also associated with a poor overall survival (5-year recurrence-free survival rate, 62% versus 84%; p<0.05) (Table 1), which was confirmed by a multivariate analysis (hazard ratio, 2.76 [95% CI, 1.14-6.71]; P=0.025). Conclusions: CTC-positivity was associated with poor recurrence-free survival and poor overall survival in resected lung cancer. [Table: see text]

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