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W. Li
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 2
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-082 - Activation of JAK1 Confers Poor Prognosis in Chinese Patients with Lung Adenocarcinoma (ID 757)
09:30 - 09:30 | Author(s): W. Li
- Abstract
Background:
Janus kinase 1 (JAK1) has been reported to activate the JAK/STAT cascade in non-small cell lung cancers (NSCLC), among which most lung adenocarcinoma (ADCC) is associated with somatic epidermal growth factor receptor (EGFR) tyrosine kinase mutations. STAT3 is considered to be one of both JAK1 and EGFR downstream pathways promoting oncogenesis. However, the association between JAK1 activation, EGFR mutations and their prognostic value on NSCLC remains unclear. This study explored relations between the activated form, p-JAK1 and prognosis in patients with NSCLC and EGFR mutations status with ADCC subjects.
Methods:
a cohort of 142 resected primary NSCLC cases including 74 ADCC and 68 squamous carcinoma (SqCC) were collected and analyzed, p-JAK1 expression was determined by immunohistolchemical (IHC) assay. EGFR FISH status was analyzed in 74 ADCC subjects. The prognostic significances of p-JAK1 and EGFR expression status were evaluated with univariate and multivariate survival analysis.
Results:
Compared with normal lung tissues, p-JAK1 expression level significantly increased in NSCLC (P=0.000). Positive p-JAK1 expression indicated poor prognosis in NSCLC, especially in early stage subjects (T1+T2, N0+N1, stage I + stage II) (All P<0.05). (P=0.001).Figure 1 p-JAK1 is an independent predictor for poor prognosis (P=0.022). Further analysis showed that significance existed only in ADCC cases but not in SqCC. Survival time for p-JAK1(+)/EGFR(+) subjects was drastically shortened than the other 3 combinations Figure 2
Conclusion:
Our results provided clinical evidence that activation of JAK1 is an independent prognostic factor in early stage NSCLC, especially in ADCC. EGFR and p-JAK1 combination could be a new target for selecting individual therapy strategies and predicting therapeutic effect for NSCLC.
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P3.04-094 - Hyperphosphorylation of Ribosomal Protein S6 Predicts Unfavorable Clinical Survival in Non-Small Cell Lung Cancer (ID 495)
09:30 - 09:30 | Author(s): W. Li
- Abstract
Background:
Ribosomal protein S6 (rpS6), a component of the 40S ribosomal subunit, is involved in multiple cellular bioactivities. However, its clinicopathological significance in non-small cell lung cancer (NSCLC) is poorly understood.
Methods:
Expressions of total rpS6 (t-rpS6) and phosphorylated rpS6 (Ser235/236, p-rpS6) were detected immunohistochemically in 316 NSCLC tissues and 82 adjacent controls, followed by statistical evaluation of the relationship between proteins expressions and patients’ survivals to identify their prognostic values. Cytological experiments with overexpressing or silencing rpS6 by lentivirus in human bronchial epithelial (HBE) or NSCLC cell lines were performed to explore potential mechanisms by which rpS6 affects the clinical development of NSCLC. Additionally, RNA interference for Akt1, Akt2 and Akt3 were performed as well to investigate the upstream regulation of rpS6.
Results:
Positive rates of t-rpS6 and p-rpS6 were both significantly increased in NSCLC tissues, compared with controls (82.9% vs 62.2% for t-rpS6; 52.2% vs 22.0% for p-rpS6; both P < 0.001). However, only hyperphosphorylation of rpS6, expressed as either elevated p-rpS6 alone or the ratio of p-rpS6 to t-rpS6 (p-rpS6/t-rpS6) no less than 0.67, was greatly associated with the unfavorable survival of NSCLC patients, especially for cases at stage I (all P < 0.001). The independent adverse prognostic value of hyperphosphorylated rpS6 was confirmed by multivariate Cox regression analysis (hazard ratios for elevated p-rpS6 alone and p-rpS6/t-rpS6 no less than 0.67 were 2.403, 4.311 respectively, both P < 0.001). Overexpression or knockdown of rpS6, along with parallel alterations of p-rpS6, led to increased or decreased cells proliferations respectively, which were dependent on redistributions of cell cycles (all P < 0.05). Cells migration and invasion also changed with rpS6 interference (all P < 0.05). Furthermore, upstream overexpression or knockdown of Akt2, rather than Akt1 or Akt3, resulted in striking hyperphosphorylation or dephosphorylation of mTOR, p70S6K and rpS6 (all P < 0.05). These might be the underlying mechanisms in which rpS6 overactivation promotes the development of NSCLC.
Conclusion:
Hyperphosphorylation of rpS6, probably regulated by the Akt2/mTOR/p70S6K signaling pathway, is closely relevant to the progression of NSCLC and it might be served as a promising therapeutic target for NSCLC treatment.
