Distinct outcome of stage I lung adenocarcinoma with ACTN4 cell motility gene amplification

Noro, Rintaro; Honda, Kazufumi; Tsuta, Koji; Ishii, Genichiro; Maeshima, Arafumi; Miura, Naruhisa; Furuta, Koh; Shibata, Tatsuhiro; Tsuda, Hitoshi; Ochiai, Atsushi; Sakuma, Tomohiro; Nishijima, Nobuhiko; Gemma, Akihiko; Asamura, Hisao; Nagai, Kanji; Yamada, Tesshi

doi:10.1093/annonc/mdt293

Cited by 42 publications

(67 citation statements)

References 24 publications

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“…High expression levels of excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase subunit M2 (RRM2), and thymidylate synthase (TS) were suggested as negative prognostic factors for patients with resected NSCLC (33,34). In addition, cyclooxygenase-2 and amplification of the actin-4 (ACTN4) gene were considered markers for a poor prognosis in stage I disease (35,36). However, a conceivable prognostic biomarker for patients with stage I AD has not yet been established.…”

Section: Univariate Analysis Multivariate Analysismentioning

confidence: 99%

AXL and GAS6 co-expression in lung adenocarcinoma as a prognostic classifier

et al. 2017

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Abstract. AXL, a receptor tyrosine kinase implicated in cell survival, proliferation, and migration, is also associated with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor therapy. However, its prognostic significance in lung adenocarcinoma (AD) remains unclear. We therefore evaluated the prognostic significance of the expression of AXL and/or its ligand, growth arrestspecific 6 (GAS6), in completely resected lung AD. We evaluated the relationship between AXL, GAS6, and vimentin expression, as determined by immunohistochemistry (IHC) analysis, with overall survival and disease-free survival in 113 patients with stages I-III lung AD. Protein expression was also assayed using western blot analysis in 10 lung AD cell lines. AXL-positive (AXL

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Section: Univariate Analysis Multivariate Analysismentioning

confidence: 99%

AXL and GAS6 co-expression in lung adenocarcinoma as a prognostic classifier

et al. 2017

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“…Immunohistochemical staining for actinin-4 & assessment Formalin-fixed paraffin-embedded tissue specimens from resected lung adenocarcinomas were immunohistochemically analyzed with an anti-human actinin-4 monoclonal antibody (N-terminal actinin-4) (Abnova Corporation, Taipei, Taiwan) [17,22]. Immunoperoxidase staining was performed as described.…”

Section: Patient Datamentioning

confidence: 99%

“…Any lower level of immunoreactivity was classified as IHC negative. The criterion (>30%) for assessment of ACTN4 expression by IHC was defined according to the previous study in which we evaluated the expression status of ACTN4 in three independent cohorts totaling 1033 patients with stage I lung adenocarcinoma [22]. IHC results were judged independently by three investigators (H Shiraishi, Y Watabe and T Kakuya) who were unaware of the clinical data, and consensus was reached for any discordant cases.…”

Section: Patient Datamentioning

confidence: 99%

Actinin-4 Protein Overexpression as a Predictive Biomarker in Adjuvant Chemotherapy for Resected Lung Adenocarcinoma

Shiraishi

Fujiwara²,

Kakuya³

et al. 2017

Biomark. Med.

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Aim:Although several clinical trials demonstrated the benefits of platinum-combination adjuvant chemotherapy for stage II-IIIA lung adenocarcinoma, predictive biomarkers for the efficacy of such therapy have not yet been identified. We evaluated protein overexpression of actinin-4 as a predictive biomarker of the efficacy of adjuvant chemotherapy in resected lung adenocarcinoma. Materials & methods: We measured actinin-4 protein levels in patients with completely resected stage II-IIIA lung adenocarcinoma using immunohistochemistry and then retrospectively compared survival between adjuvant chemotherapy and observation groups. Results: A total of 148 eligible patients were classified into actinin-4 positive or negative cases by immunohistochemistry. In the former, patients with adjuvant chemotherapy survived significantly longer than those with observation (hazard ratio [HR]: 0.307; p = 0.028). But, no significant survival benefit was noted with adjuvant chemotherapy (HR: 0.926; p = 0.876) in the latter. Conclusion: This marker could predict the efficacy of adjuvant chemotherapy for resected lung adenocarcinoma patients. Non-small-cell lung cancer (NSCLC) is one of the most lethal malignancies worldwide. Surgical resection is the most potentially curative treatment and is the standard treatment choice for patients with early stage NSCLC. However, despite curative surgery, the 5-year survival of NSCLC patients is 46-64% at stage IIA, about 36-49% at stage IIB and just 25% at stage IIIA [1,2]. Several meta-analyses and randomized controlled trials, including the JBR.10 and ANITA trials, have demonstrated the efficacy of adjuvant chemotherapy for NSCLC patients [3][4][5][6]. Although adjuvant cisplatin-based chemotherapy is recommended as standard care in completely resected NSCLC patients with stage II-IIIA [7,8], the relative reduction in the risk of death of patients undergoing adjuvant chemotherapy is modest in comparison with that of patients without adjuvant chemotherapy (hazard ratio [HR] for stage II: 0.83; 95% CI: 0.73-0.95; and HR for stage III: 0.83; 95% CI: 0.72-0.94). Therefore, the identification of predictive biomarkers for the efficacy of adjuvant chemotherapy for stage II-IIIA is required in the clinical setting. To identify companion diagnostic biomarkers for adjuvant chemotherapy, numerous prognostic factors as well as predictive factors for adjuvant chemotherapy have been investigated for early stage NSCLC [9][10][11][12][13][14].

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“…Although several studies have evaluated the expression levels of ERCC1 by IHC, no consensus has been reached due to the difficulty in detecting the unique functional ERCC1 isoform (41). Actin 4 has been identified as a potential prognostic biomarker in stage I lung adenocarcinoma (42). The present study revealed that ABCB1 could be used as a prognostic marker in lung ADC patients with stage I disease, and is associated with recurrence in stage I ADC patients with wild-type EGFR.…”

Section: Discussionmentioning

confidence: 66%

“…Associations between ABCB1, ALDH1A1 and CD44 expression levels and characteristics of patients with lung adenocarcinoma. 38 (81) 10 (21) 37 (79) 27 (57) 20 (43) ≥65 81 (63) 11 (14) 70 (86) 33 (41) 48 (59) 40 (49) 41 ( 13 (19) 54 (81) 27 (40) 40 (60) 39 (58) 28 (42) Female 61 (48) 7 (11) 54 (89) 16 (26) 45 (74) 28 (46) 33 ( (16) 67 (84) 27 (34) 53 (66) 47 (59) 33 (41) No 47 (37) 7 (15) 40 (85) 16 (34) 31 (66) 20 (43) 27 ( (17) 4 (10) 38 (90) 7 (17) 35 (83) 26 (62) 16 (38) 2+3 86 (83) 16 (19) 70 (81) 36 (42) 50 (58) 41 (48) 45 ( (31) 8 (20) 32 (80) 12 (30)...…”

Section: Prognostic Significance Of Abcb1 Expression In Stage Imentioning

confidence: 99%

Prognostic significance of ABCB1 in stage I lung adenocarcinoma

et al. 2017

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Abstract. Cancer stem cell (CSC) properties have been recently proposed to explain tumor carcinogenesis and multidrug resistance in several human cancers, including non-small cell lung cancer (NSCLC). The present study examined the protein expression of three CSC-associated markers, namely ATP binding cassette subfamily B member 1 (ABCB1), aldehyde dehydrogenase 1 family member A1 (ALDH1A1) and cluster of differentiation (CD) 44, by immunohistochemistry in 194 NSCLC patients who underwent complete resection of NSCLC tumors. The association between the expression of these proteins and patient prognosis was evaluated to clarify the prognostic significance of CSC-associated markers in NSCLC patients. Positive staining for ABCB1 demonstrated a trend toward worse survival compared with negative staining in stage I-III NSCLC. Negative staining for ALDH1 or CD44 exhibited a trend toward worse survival compared with positive staining in stage I-III NSCLC. It was observed that patients with stage I lung adenocarcinoma (ADC) showing positivity for ABCB1 expression had significantly poorer survival than those with negative ABCB1 staining (P=0.03). Furthermore, stage I ADC patients with wild-type epidermal growth factor receptor (EGFR) who exhibited positive staining for ABCB1 had significantly shorter disease-free survival (DFS) compared with patients with negative staining for ABCB1 (P<0.01). Analyses by univariate and multivariate Cox proportional hazards models revealed that ABCB1-positive staining was significantly associated with DFS and was an independent prognostic factor (hazard ratio, 3.49; P<0.05) in these patients. These results suggest that ABCB1 protein expression is useful for predicting prognosis and selecting patients for post-operative therapy in stage I lung ADC patients, particularly those harboring wild-type EGFR.

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Distinct outcome of stage I lung adenocarcinoma with ACTN4 cell motility gene amplification

Abstract: Amplification of the ACTN4 gene defines a small but substantial subset of patients with stage I lung adenocarcinoma showing a distinct outcome. Such patients require intensive medical attention and might benefit from postoperative adjuvant chemotherapy.

Cited by 42 publications

References 24 publications

AXL and GAS6 co-expression in lung adenocarcinoma as a prognostic classifier

AXL and GAS6 co-expression in lung adenocarcinoma as a prognostic classifier

Actinin-4 Protein Overexpression as a Predictive Biomarker in Adjuvant Chemotherapy for Resected Lung Adenocarcinoma

Prognostic significance of ABCB1 in stage I lung adenocarcinoma

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