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Lung cancer biomarkers

Guo-Jin Wu, Jun Pen, Ying Huang, Su An, Ying Liu, Yang Yang, Qian Hao, Xiao-Xi Guo, Tian-Rui Xu
Aberrant activation of the Raf-MEK-ERK pathway has frequently been associated with various cancers, especially lung cancer. However, the key regulators of this pathway are largely unknown. Using functional proteomics screening, we found that KAP1 interacts with c-Raf. Knocking out KAP1 decreased c-Raf phosphorylation at serine 259 and increased its phosphorylation at serine 338, which activated MEK and ERK. We detected higher KAP1 expression in lung cancer tissues than in normal peri-tumoral tissues. KAP1 knockdown arrested A549 lung cancer cells in the G0/G1 phase of the cell cycle and attenuated cell growth, metastasis, the epithelial-mesenchymal transition, angiogenesis, stemness, and colony formation...
June 19, 2018: Molecular Carcinogenesis
Lu-Nan Qi, Bang-De Xiang, Fei-Xiang Wu, Jia-Zhou Ye, Jian-Hong Zhong, Yan-Yan Wang, Yuan-Yuan Chen, Zu-Shun Chen, Liang Ma, Jie Chen, Wen-Feng Gong, Ze-Guang Han, Yan Lu, Jin-Jie Shang, Le-Qun Li
To clarify the significance of circulating tumor cells (CTC) undergoing epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) patients, we used an advanced CanPatrol™ CTC-enrichment technique and in situ hybridization (ISH) to enrich and classify CTC from blood samples. 101 of 112 (90.18%) HCC patients were CTC-positive, even with early-stage disease. CTC were also detected in 2 of 12 hepatitis B virus (HBV) patients, both of whom had small HCC tumors detected within 5 months. CTC count ≥16 and mesenchymal-CTC (M-CTC) percentage ≥2% prior to resection were significantly associated with early recurrence, multi-intrahepatic recurrence, and lung metastasis...
June 18, 2018: Cancer Research
Lei Lei, Zhiming Jiang, Gu Zhang, Qiaoyuan Cheng, Hongyang Lu
BACKGROUND: The response to temozolomide (TMZ) treatment in small-cell lung cancer (SCLC) correlated with O(6)-methylguanine -DNA methyltransferase (MGMT) promoter methylation. 1p/19q co-deletion within oligodendroglioma is a responsive predictor for TMZ. Currently, the status of MGMT promoter methylation and 1p/19q co-deletion in pulmonary carcinoid (PC) and large-cell neuroendocrine carcinoma (LCNEC) is not reported. METHODS: Nine PC [two atypical carcinoids (AC), seven typical carcinoids (TC)] and six LCNEC patients were collected retrospectively...
June 18, 2018: World Journal of Surgical Oncology
Tamkin Ahmadzada, Steven Kao, Glen Reid, Michael Boyer, Annabelle Mahar, Wendy A Cooper
It is now widely established that management of lung cancer is much more complex and cannot be centered on the binary classification of small-cell versus non-small cell lung cancer (NSCLC). Lung cancer is now recognized as a highly heterogeneous disease that develops from genetic mutations and gene expression patterns, which initiate uncontrolled cellular growth, proliferation and progression, as well as immune evasion. Accurate biomarker assessment to determine the mutational status of driver mutations such as EGFR , ALK and ROS1 , which can be targeted by specific tyrosine kinase inhibitors, is now essential for treatment decision making in advanced stage NSCLC and has shifted the treatment paradigm of NSCLC to more individualized therapy...
June 15, 2018: Journal of Clinical Medicine
B Melosky
Background: The treatment paradigm for metastatic nonsquamous non-small-cell lung cancer (nsclc) continues to change. Algorithms published only 6 months ago are outdated today and are dramatically different from those published a few years ago. New driver mutations continue to be identified, and the development of therapies to inhibit oncogenic addiction is ongoing. Patient survival is improving as treatments become more personalized and effective. Methods: This review looks at the outcomes of recent trials and discusses treatment options for patients with metastatic nsclc of nonsquamous histology...
June 2018: Current Oncology
A Alshangiti, G Chandhoke, P M Ellis
Angiogenesis is frequent in non-small-cell lung cancer (nsclc) and is associated with more aggressive disease. Many clinical trials have evaluated the addition of antiangiogenic therapy to standard therapies for patients with nsclc. Bevacizumab, a monoclonal antibody directed against serum vascular endothelial growth factor, in combination with carboplatin-paclitaxel chemotherapy, has been shown to improve survival for patients with nsclc. However, bevacizumab-based therapy is not suitable for many nsclc patients, including those with squamous histology, poor performance status, brain metastases, and the presence of bleeding or thrombotic disorders...
June 2018: Current Oncology
M Cabanero, M S Tsao
The advent of targeted therapy in non-small-cell lung cancer (nsclc) has made the routine molecular diagnosis of EGFR mutations crucial for optimal patient management. Obtaining tumour tissue for biomarker testing, especially in the setting of re-biopsy, can present many challenges. A potential alternative source of tumour dna is circulating cell-free tumour-derived dna (ctdna). Although ctdna is present in low quantities in plasma, the convenience of sample acquisition and the increasing reliability of detection methods make this approach a promising one...
June 2018: Current Oncology
Catarina Veiga, David Landau, Anand Devaraj, Tom Doel, Jared White, Yenting Ngai, David J Hawkes, Jamie R McClelland
BACKGROUND: and Purpose: Recent improvements in lung cancer survival have spurred an interest in understanding and minimizing long term radiation-induced lung damage (RILD). However, there is still no objective criteria to quantify RILD leading to variable reporting across centres and trials. We propose a set of objective imaging biomarkers to quantify common radiological findings observed 12-months after lung cancer radiotherapy (RT). MATERIAL AND METHODS: Baseline and 12-month CT scans of 27 patients from a phase I/II clinical trial of isotoxic chemoradiation were included in this study...
June 14, 2018: International Journal of Radiation Oncology, Biology, Physics
Foyez Mahmud, Ok-Cheol Jeon, Farzana Alam, Ruby Maharjan, Jeong Uk Choi, Jooho Park, Sojung Lee, Jin Woo Park, Dong Soo Lee, Youngro Byun
There is a growing interest in preclinical research to consider low-dose metronomic chemotherapy as antiangiogenic cancer treatment. Oral metronomic therapy, in particular, has shown much promise with its ease of daily administration and higher therapeutics window. In that regard, we developed oral pemetrexed using the physical complex with the bile acid enhancers (DCK). In a caco-2 permeability study, the oral pemetrexed/DCK complex had significantly higher drug uptake, and inhibited efflux transporter activity as well...
June 13, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
M Catherine Pietanza, Saiama N Waqar, Lee M Krug, Afshin Dowlati, Christine L Hann, Alberto Chiappori, Taofeek K Owonikoko, Kaitlin M Woo, Robert J Cardnell, Junya Fujimoto, Lihong Long, Lixia Diao, Jing Wang, Yevgeniva Bensman, Brenda Hurtado, Patricia de Groot, Erik P Sulman, Ignacio I Wistuba, Alice Chen, Martin Fleisher, John V Heymach, Mark G Kris, Charles M Rudin, Lauren Averett Byers
Purpose Both temozolomide (TMZ) and poly (ADP-ribose) polymerase (PARP) inhibitors are active in small-cell lung cancer (SCLC). This phase II, randomized, double-blind study evaluated whether addition of the PARP inhibitor veliparib to TMZ improves 4-month progression-free survival (PFS). Patients and Methods A total of 104 patients with recurrent SCLC were randomly assigned 1:1 to oral veliparib or placebo 40 mg twice daily, days 1 to 7, and oral TMZ 150 to 200 mg/m2 /day, days 1 to 5, of a 28-day cycle until disease progression, unacceptable toxicity, or withdrawal of consent...
June 15, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
P D Bonomi, D Gandara, F R Hirsch, K M Kerr, C Obasaju, L Paz-Ares, C Bellomo, J D Bradley, P A Bunn, M Culligan, J R Jett, E S Kim, C J Langer, R B Natale, S Novello, M Pérol, S S Ramalingam, M Reck, C H Reynolds, E F Smit, M A Socinski, D R Spigel, J F Vansteenkiste, H Wakelee, N Thatcher
Background: Upregulated expression and aberrant activation of the epidermal growth-factor receptor (EGFR) are found in lung cancer, making EGFR a relevant target for non-small-cell lung cancer (NSCLC). Treatment with anti-EGFR monoclonal antibodies (mAbs) is associated with modest improvement in overall survival in patients with squamous cell lung cancer (SqCLC) who have a significant unmet need for effective treatment options. While there is evidence that using EGFR gene copy number, EGFR mutation, and EGFR protein expression as biomarkers can help select patients who respond to treatment, it is important to consider biomarkers for response in patients treated with combination therapies that include EGFR mAbs...
June 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Zhan Shi, Jiaxin Chen, Xiangmin Zhang, Jian Chu, Zhitao Han, Da Xu, Sishun Gan, Xiuwu Pan, Jianqing Ye, Xingang Cui
Human Ataxin-3 protein was first identified as a transcript from patients with Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3). Recent studies have demonstrated that Ataxin-3 is involved in gastric cancer and lung cancer. However, the role of Ataxin-3 in testicular cancer (TC) remains poorly understood. This study aims to explore the significance of Ataxin-3 expression in TC. Firstly, we investigated 53 paired TC and para-tumor tissues and found that Ataxin-3 was overexpressed in TC tissues, and this overexpression of Ataxin-3 was correlated with tumor stages...
June 11, 2018: Biochemical and Biophysical Research Communications
Liang Xia, Linlin Wu, Jing Bao, Qingsheng Li, Xiaowen Chen, Hailong Xia, Ruixiang Xia
Circular RNA (circRNA) belongs to the non-coding RNA family and is involved in various human cancers, such as lung cancer and colorectal cancer. Nevertheless, whether circRNA expression is related to chronic lymphocytic leukemia (CLL) progression remains largely unclear. In our study, we investigated the role of circ-CBFB in CLL. We found that circ-CBFB was markedly overexpressed in CLL cells compared to normal controls. Furthermore, we found that circ-CBFB could serve as a diagnostic and prognostic biomarker for CLL patients...
June 11, 2018: Biochemical and Biophysical Research Communications
Peter P Luk, Christina I Selinger, Annabelle Mahar, Wendy A Cooper
CONTEXT: - A small proportion of non-small cell lung cancers harbor rearrangements of ALK or ROS1 genes, and these tumors are sensitive to targeted tyrosine kinase inhibitors. It is crucial for pathologists to accurately identify tumors with these genetic alterations to enable patients to access optimal treatments and avoid unnecessary side effects of less effective agents. Although a number of different techniques can be used to identify ALK- and ROS1-rearranged lung cancers, immunohistochemistry and fluorescence in situ hybridization are the mainstays...
June 14, 2018: Archives of Pathology & Laboratory Medicine
Tricia L Larose, Florence Guida, Anouar Fanidi, Arnulf Langhammer, Kristian Kveem, Victoria L Stevens, Eric J Jacobs, Stephanie A Smith-Warner, Edward Giovannucci, Demetrius Albanes, Stephanie J Weinstein, Neal D Freedman, Ross Prentice, Mary Pettinger, Cynthia A Thomson, Qiuyin Cai, Jie Wu, William J Blot, Alan A Arslan, Anne Zeleniuch-Jacquotte, Loic Le Marchand, Lynne R Wilkens, Christopher A Haiman, Xuehong Zhang, Meir J Stampfer, Allison M Hodge, Graham G Giles, Gianluca Severi, Mikael Johansson, Kjell Grankvist, Renwei Wang, Jian-Min Yuan, Yu-Tang Gao, Woon-Puay Koh, Xiao-Ou Shu, Wei Zheng, Yong-Bing Xiang, Honglan Li, Qing Lan, Kala Visvanathan, Judith Hoffman Bolton, Per Magne Ueland, Øivind Midttun, Neil Caporaso, Mark Purdue, Howard D Sesso, Julie E Buring, I-Min Lee, J Michael Gaziano, Jonas Manjer, Hans Brunnström, Paul Brennan, Mattias Johansson
Background: Self-reported smoking is the principal measure used to assess lung cancer risk in epidemiological studies. We evaluated if circulating cotinine-a nicotine metabolite and biomarker of recent tobacco exposure-provides additional information on lung cancer risk. Methods: The study was conducted in the Lung Cancer Cohort Consortium (LC3) involving 20 prospective cohort studies. Pre-diagnostic serum cotinine concentrations were measured in one laboratory on 5364 lung cancer cases and 5364 individually matched controls...
June 12, 2018: International Journal of Epidemiology
Ashley Volaric, Ryan Gentzler, Richard Hall, James H Mehaffey, Edward B Stelow, Timothy N Bullock, Linda W Martin, Anne M Mills
The immune regulatory enzyme indoleamine-2,3-dioxygenase (IDO-1) suppresses T cell responses and may reduce efficacy of therapies targeting immune checkpoints such as programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1). Early phase clinical trials combining IDO-1 and PD-1/PD-L1 inhibitors have shown some promise in non-small cell lung cancers (NSCLCs). However, the coexpression of IDO-1 and PD-L1 has not been thoroughly investigated, and the potential for IDO-1 immunohistochemical expression as a therapeutic biomarker is unknown...
June 12, 2018: American Journal of Surgical Pathology
Ying Ji, Jinquan Jiang, Lihua Huang, Wei Feng, Zhang Zhang, Longyu Jin, Xiaowei Xing
Lung cancer is the most common cause of cancer‑related deaths, and early diagnosis and targeted therapy are extremely important in the treatment of this disease. Sperm‑associated antigen 4 (SPAG4) was recently found to be a novel cancer biomarker. In the present study, the expression of SPAG4 was revealed to be high in lung adenocarcinoma tissues as determined by western blotting and immunohistochemistry. SPAG4 knockdown by RNAi efficiently reduced the migration of the lung cancer A549 cells in vitro...
June 4, 2018: Oncology Reports
Debasis Patnaik, Pierre-Olivier Estève, Sriharsa Pradhan
Ubiquitin-like containing PHD Ring Finger 1 (UHRF1) is a multi-domain protein with a methyl-DNA binding SRA (SET and RING-associated) domain, required for maintenance DNA methylation mediated by DNMT1. Primarily expressed in proliferating cells, UHRF1 is a cell-cycle regulated protein that is required for S phase entry. Furthermore, UHRF1 participates in transcriptional gene regulation by connecting DNA methylation to histone modifications. Upregulation of UHRF1 may serve as a biomarker for a variety of cancers; including breast, gastric, prostate, lung and colorectal carcinoma...
May 25, 2018: Oncotarget
Ravi Salgia, Isa Mambetsariev, Blake Hewelt, Srisairam Achuthan, Haiqing Li, Valeriy Poroyko, Yingyu Wang, Martin Sattler
Mathematical cancer models are immensely powerful tools that are based in part on the fractal nature of biological structures, such as the geometry of the lung. Cancers of the lung provide an opportune model to develop and apply algorithms that capture changes and disease phenotypes. We reviewed mathematical models that have been developed for biological sciences and applied them in the context of small cell lung cancer (SCLC) growth, mutational heterogeneity, and mechanisms of metastasis. The ultimate goal is to develop the stochastic and deterministic nature of this disease, to link this comprehensive set of tools back to its fractalness and to provide a platform for accurate biomarker development...
May 25, 2018: Oncotarget
Terunaga Inage, Takahiro Nakajima, Sakae Itoga, Takayuki Ishige, Taiki Fujiwara, Yuichi Sakairi, Hironobu Wada, Hidemi Suzuki, Takekazu Iwata, Masako Chiyo, Shigetoshi Yoshida, Kazuyuki Matsushita, Kazuhiro Yasufuku, Ichiro Yoshino
BACKGROUND: The limited negative predictive value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has often been discussed. OBJECTIVE: The aim of this study was to identify a highly sensitive molecular biomarker for lymph node staging by EBUS-TBNA. METHODS: Five microRNAs (miRNAs) (miR-200a, miR-200b, miR-200c, miR-141, and let-7e) were selected as biomarker candidates for the detection of nodal metastasis in a miRNA expression analysis...
June 13, 2018: Respiration; International Review of Thoracic Diseases
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