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Abstract Background Hyperfibrinogenemia is a common problem associated with various carcinomas, and is accompanied by hypercoagulablity. In advanced non-small-cell lung cancer (NSCLC) it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to chemotherapeutic response and prognosis. The purposes of this study were to: 1) analyze the association between chemotherapy-induced changes in plasma fibrinogen level and the chemotherapeutic response after the first two courses of standard first-line platinum-based chemotherapy; and 2) evaluate the prognostic significance of the basal plasma fibrinogen level in patients with advanced NSCLC. Methods In this retrospective study, the data from 160 patients with advanced NSCLC were collected. The association between the changes in fibrinogen and the response to chemotherapy, or between the pre-and post-chemotherapy fibrinogen levels and patient clinical characteristics, were analyzed using SPSS software. In addition, the prognostic value of pre-chemotherapy fibrinogen levels was assessed. Results The median pre-chemotherapy plasma fibrinogen level was 4.4 g/L. Pre-chemotherapy plasma fibrinogen levels correlated significantly with gender (p = 0.041). Post-chemotherapy plasma fibrinogen levels correlated with gender (p = 0.023), age (p = 0.018), ECOG (p = 0.002) and tumor response (p = 0.049). Plasma fibrinogen levels markedly decreased after chemotherapy in 98 (61.25 %) patients with pre-chemotherapy hyperfibrinogenemia (p = 0.008); and in this population there was a significant link between the decrease in fibrinogen level, and initial partial response (PR; p = 0.017) and stable disease (SD; p = 0.031). Univariate and multivariate analysis revealed that higher levels of fibrinogen (≥4.4 g/L) and ECOG 1 were positively associated with shorter overall survival (OS). CEA and CA125 also decreased significantly (p =0.015, p =0.000) in DCR group after chemotherapy. Conclusions This study showed that the reduction in plasma fibrinogen levels induced by chemotherapy might be as a promising biomarker as CEA and CA125 for evaluating the efficacy of chemotherapy in advanced NSCLC. In addition, basal plasma fibrinogen levels could be used as an independent prognostic parameter for the OS of patients with advanced NSCLC.

BACKGROUND: Occludin/ELL domain containing 1 (OCEL1) is a novel discovered protein with its molecular functions remaining unknown and its role in lung cancer has not been directly explored. OBJECTIVES: This study focused on the role of OCEL1 in the progression and prognosis of non-small cell lung cancer (NSCLC). METHODS: A public database and tissue samples (80 NSCLC tissue samples and paired normal lung samples) were used to compare differences in OCEL1 expression and investigate its relationship with clinical characteristics and prognosis. RESULTS: Compared to adjacent normal lung tissue samples, OCEL1 expression was significantly down-regulated in tumor tissues. In addition, there was a negative correlation between OCEL1 and Ki67 expression levels. Low OCEL1 expression was significantly associated with lymph node metastasis, higher TNM stage, and poor prognosis. Importantly, multivariate analysis identified OCEL1 expression as an independent predictor for unfavorable NSCLC prognosis. CONCLUSIONS: These results indicated that OCEL1 protein may serve as a novel prognostic biomarker in NSCLC. [ABSTRACT FROM AUTHOR]

Although epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) could greatly improve the prognosis of NSCLC patients harboring activating EGFR mutations, drug resistance still remains a major obstacle to successful treatment. Our previous study found that the EGFR‐TKI icotinib could upregulate the expression of Casitas‐B‐lineage lymphoma protein‐B (Cbl‐b), an E3 ubiquitin ligase. In the present study, we aimed to clarify the potential role of Cbl‐b in the resistance to icotinib, and the underlying mechanisms using EGFR‐mutant cell lines. We found that icotinib inhibited the proliferation of mutant‐EGFR NSCLC cells (PC9 and HCC827), and upregulated the expression of Cbl‐b at both the protein and mRNA levels. Cbl‐b knockdown decreased the sensitivity of PC9 and HCC827 cells to icotinib, and partially restored icotinib‐inhibited AKT activation in PC9 cells. On the contrary, Cbl‐b overexpression could partly reverse the drug resistance in PC9 icotinib‐resistant cells (PC9/IcoR). Moreover, overexpressing p65, the main member of transcription factor NF‐κB family, reversed the icotinib‐mediated upregulation of Cbl‐b. Collectively, these data suggest that icotinib could upregulate Cbl‐b mediated by NF‐κB inhibition, and Cbl‐b contribute to the icotinib sensitivity in EGFR‐mutant NSCLC cells. This study highlights that low expression of Cbl‐b might be the key obstacles in the efficacy of icotinib therapy. [ABSTRACT FROM AUTHOR]

Abstract: Tyrosine kinase Inhibitors (TKIs) of epidermal growth factor receptor (EGFR) has considerably benefited for non‐small cell lung carcinomas (NSCLC) harbor mutations in EGFR. However, the factors attenuating EGFR‐TKI efficiency are obstacles to inhibit the proliferation of EGFR‐mutant NSCLC cells successfully. Clarifying the insensitivity mechanisms of EGFR‐TKI would help to develop new treatment strategy. In this study, the sensitivity of EGFR‐mutant NSCLC cell lines, PC9 and HCC827, to icotinib was detected. Similar with other EGFR‐TKIs such as gefitinib and erlortinib in previous research, the proliferation of two cell lines was apparently inhibited. However, we surprisingly found that contrast with the suppression of EGFR‐AKT/ERK pathway, STAT3 was significantly activated in PC9 cells with the treatment of icotinib, but not in HCC827 cells. Further study confirmed that icotinib concomitantly induced IL‐6 secretion and src activation in PC9 cells. Moreover, with the treatment of IL‐6 neutralizing antibody or src inhibitor, dasatinib, icotinib‐induced phosphorylation of STAT3 was reduced, as well as the sensitivity of PC9 to icotinib was also partially increased. Our results suggest that Src/IL‐6/STAT3 bypass pathway is activated to maintain cell survival when the EGFR pathway was inhibited by TKIs, even in some EGFR‐mutant NSCLC cells sensitive to TKIs. This finding provides a groundwork for potential combinatorial treatment with TKIs and Src or STAT3 inhibitor to improve icotinib sensitivity. [ABSTRACT FROM AUTHOR]

Despite considerable advances in chemotherapy, radiotherapy, target therapy, and biological therapy, the prognosis for those with resected non-small-cell lung cancer (NSCLC) has not substantially improved. It was recently reported that two receptors, Notch-1 and c-Met, correlate directly or indirectly with the initiation and development of malignant tumors, such as lung cancer; however, the prognostic value of coexpression of these receptors and their relationship in resected NSCLC was not clear. In this study, the expression levels of Notch-1 and c-Met in 117 patients with resected NSCLC were assessed using immunohistochemistry (IHC). The results showed that the positive expression rate of Notch-1 in total patients was 59.8 %. The positive expression rate of c-Met in the all population was 69.2 %. In addition, a significant positive association was shown between Notch-1 and c-Met ( P < 0.001). Simultaneously, patients with coexpression of both receptors had a significantly poorer prognosis than those without coexpression ( P < 0.001). Multivariate analysis showed that T stage ( P = 0.016) and c-Met expression ( P < 0.001) were independent prognostic factors. In conclusion, coexpression of both receptors correlates with poorer prognosis in patients with resected NSCLC. Targeting both receptors simultaneously may prove a more effective antitumor strategy. Patients with coexpression of both receptors might benefit from cotargeting Notch-1 and c-Met. [ABSTRACT FROM AUTHOR]

G-protein-signaling modulator 2 (GPSM2) belongs to a protein family that regulates activation of G proteins and plays an important role in mitotic spindle orientation. However, the role of GPSM2 in lung adenocarcinoma (LUAD) is still unclear. In this study, it was found that GPSM2 correlates with clinicopathological features and patient's prognosis in LUAD. Knocking down GPSM2 promoted LUAD cell proliferation in vitro and in vivo. Mechanistically, it was demonstrated that GPSM2 knockdown accelerates cell proliferation via the EGFR pathway. These results confirmed that GPSM2 played an important role in LUAD. Moreover, GPSM2, as an independent prognostic factor, may serve as a potential drug target and prognostic biomarker in LUAD. [ABSTRACT FROM AUTHOR]