Proteins involved in DNA damage response pathways and survival of stage I non-small-cell lung cancer patients

Choi, Chang‐Min; Yang, Seung Wook; Jo, Hanik; Song, Sang‐Yun; Jeon, Young June; Jang, Tae Won; Kim, D. J.; Jang, Seung Hun; Yang, Sei Hoon; Kim, Y. D.; Lee, K. H.; Jang, Se Jin; Kim, Y. T.; Kim, D. K.; Chung, Doo Hyun; Kim, L.; Nam, Hae Yun; Cho, J. H.; Kim, H. J.; Ryu, Jeong Seon

doi:10.1093/annonc/mdr606

Cited by 25 publications

(16 citation statements)

References 25 publications

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“…The relative expression of the four genes was similar in adeno- and large cell carcinomas but, in comparison to these, it was significantly increased in squamous cell carcinomas, in line with previously published data [4,40]. Apparently, the expression of these genes did not predict for the outcome of adenocarcinoma patients in our series, in line with recent reports with immunohistochemistry for Ercc1 and Brca1 [44,45]. …”

Section: Discussionsupporting

confidence: 90%

Expression of DNA repair and replication genes in non-small cell lung cancer (NSCLC): a role for thymidylate synthetase (TYMS)

et al. 2012

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BackgroundBRCA1 (B), ERCC1 (E), RRM1 (R) and TYMS (T) mRNA expression has been extensively studied with respect to NSCLC patient outcome upon various chemotherapy agents. However, these markers have not been introduced into clinical practice yet. One of the reasons seems to be lack of a standard approach for the classification of the reported high/low mRNA expression. The aim of this study was to determine the prognostic/predictive impact of B, E, R, T in routinely-treated NSCLC patients by taking into account the expression of these genes in the normal lung parenchyma.MethodsB, E, R, T mRNA expression was examined in 276 NSCLC samples (real-time PCR). The normal range of B, E, R, T transcript levels was first determined in matched tumor – normal pairs and then applied to the entire tumor series. Four main chemotherapy categories were examined: taxanes-without-platinum (Tax); platinum-without-taxanes (Plat); taxanes/platinum doublets (Tax/Plat); and, all-other combinations.ResultsIn comparison to remotely located normal lung parenchyma, B, E, R, T mRNA expression was generally increased in matched tumors, as well as in the entire tumor series. Therefore, tumors were classified as expressing normal or aberrant B, E, R, T mRNA. In general, no marker was associated with overall and progression free survival (OS, PFS). Upon multivariate analysis, aberrant intratumoral TYMS predicted for shorter PFS than normal TYMS in 1st line chemo-naïve treated patients (p = 0.012). In the same setting, specific interactions were observed for aberrant TYMS with Plat and Tax/Plat (p = 0.003 and p = 0.006, respectively). Corresponding patients had longer PFS in comparison to those treated with Tax (Plat: HR = 0.234, 95% CI:0.108-0.506, Wald’s p < 0.0001; Tax/Plat: HR = 0.242, 95% CI:0.131-0.447, Wald’s p < 0.0001). Similar results were obtained for PFS in 1st line chemo-naïve and (neo)adjuvant pre-treated patients. Adenocarcinoma, early disease stage, and treatment with Tax/Plat doublets independently predicted for prolonged OS in patients who received only one line of treatment (adjuvant or 1st line).ConclusionClassifying intratumoral B, E, R, T mRNA expression in comparison to normal lung may facilitate standardization of these parameters for prospective studies. With this approach, NSCLC patients with aberrant intratumoral TYMS expression will probably fare better with platinum-based treatments.

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Section: Discussionsupporting

confidence: 90%

Expression of DNA repair and replication genes in non-small cell lung cancer (NSCLC): a role for thymidylate synthetase (TYMS)

et al. 2012

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“…Such biomarkers are available and will be studied in the future for lung cancer detection (Choi et al, 2012; Takenaka et al, 2011; Tretiakova et al, 2011; Pesta et al, 2011; Lee et al, 2012; Tong et al, 2012; Ohira et al, 2003). Physical methods to further increase PC microcavity sensitivity are being investigated including optimization of PC microcavity length, the slow light effect in coupled PC waveguides and PC microcavity resonance mode quality factors (Chakravarty et al, 2012; Lai et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

Multiplexed specific label-free detection of NCI-H358 lung cancer cell line lysates with silicon based photonic crystal microcavity biosensors

Chakravarty¹,

Lai²,

Zou³

et al. 2013

Biosensors and Bioelectronics

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We experimentally demonstrate label-free photonic crystal (PC) microcavity biosensors in silicon-on-insulator (SOI) to detect the epithelial-mesenchymal transition (EMT) transcription factor, ZEB1, in minute volumes of sample. Multiplexed specific detection of ZEB1 in lysates from NCI-H358 lung cancer cells down to an estimated concentration of 2 cells per micro-liter is demonstrated. L13 photonic crystal microcavities, coupled to W1 photonic crystal waveguides, are employed in which resonances show high Q in the bio-ambient phosphate buffered saline (PBS). When the sensor surface is derivatized with a specific antibody, the binding of the corresponding antigen from a complex whole-cell lysate generates a change in refractive index in the vicinity of the photonic crystal microcavity, leading to a change in the resonance wavelength of the resonance modes of the photonic crystal microcavity. The shift in the resonance wavelength reveals the presence of the antigen. The sensor cavity has a surface area of ~11 μm2. Multiplexed sensors permit simultaneous detection of many binding interactions with specific immobilized antibodies from the same bio-sample at the same instant of time. Specificity was demonstrated using a sandwich assay which further amplifies the detection sensitivity at low concentrations. The device represents a proof-of-concept demonstration of label-free, high throughput, multiplexed detection of cancer cells with specificity and sensitivity on a silicon chip platform.

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“…Nuclear and cytoplasmic RRM1 protein expression was evaluated by light microscopy (magnification ×400), and protein expression was scored by use of a semiquantitative H ‐score, as previously described by Olaussen et al ., and successfully used for RRM1 and other putative predictive biomarkers in NSCLC by our group and other groups . Application of a scoring system that has been used in previous studies of RRM1 protein expression enables, to some degree, comparability between studies.…”

Section: Methodsmentioning

confidence: 98%

Differences in RRM1 protein expression between diagnostic biopsies and resection specimens, and changes during carboplatin and paclitaxel treatment, in non‐small‐cell lung cancer

2013

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The substantial discordance between paired samples emphasizes the need for sufficient tumour tissue in biopsies when RRM1 expression is evaluated. No change in RRM1 expression was observed in primary tumours, but expression seemed to be higher in N2 lymph node metastases following chemotherapy. Tumour heterogeneity and potential post-chemotherapy changes should be considered when RRM1 expression is evaluated.

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Proteins involved in DNA damage response pathways and survival of stage I non-small-cell lung cancer patients

Cited by 25 publications

References 25 publications

Expression of DNA repair and replication genes in non-small cell lung cancer (NSCLC): a role for thymidylate synthetase (TYMS)

Expression of DNA repair and replication genes in non-small cell lung cancer (NSCLC): a role for thymidylate synthetase (TYMS)

Multiplexed specific label-free detection of NCI-H358 lung cancer cell line lysates with silicon based photonic crystal microcavity biosensors

Differences in RRM1 protein expression between diagnostic biopsies and resection specimens, and changes during carboplatin and paclitaxel treatment, in non‐small‐cell lung cancer

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