Integrin expression profiling identifies integrin alpha5 and beta1 as prognostic factors in early stage non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Selection of early stage non-small cell lung cancer patients with a high risk of recurrence is warranted in order to select patients who will benefit from adjuvant treatment strategies. We evaluated the prognostic value of integrin expression profiles in a retrospective study on frozen primary tumors of 68 patients with early stage non-small cell lung cancer.</p> <p>Methods</p> <p>A retrospective study was performed on frozen primary tumors of 68 early stage non-small cell lung cancer patients with a follow up of at least 10 years. From all tumor tissues, RNA was isolated and reverse transcribed into cDNA. qPCR was used to generate mRNA expression profiles including integrins alpha1, 2, 3, 4, 5, 6, 7, 11, and V as well as integrins beta1, 3, 4, 5, 6, and 8.</p> <p>Results</p> <p>The expression levels of integrins alpha5, beta1 and beta3 predicted overall survival and disease free survival in early stage NSCLC patients. There was no association between integrin expression and lymph node metastases. Comparison between the histological subtypes revealed a distinct integrin signature for squamous cell carcinoma while the profiles of adenocarcinoma and large cell carcinoma were largely the same.</p> <p>Conclusion</p> <p>Integrin expression in NSCLC is important for the development and behavior of the tumor and influences the survival of the patient. Determining the integrin expression profile might serve as a tool in predicting the prognosis of individual patients.</p

Biomarkers in non-small cell lung cancer:focus on angiogenesis

In roughly forty percent of patients who undergo surgery for non-small cell lung cancer, the original tumour will return within two years of surgery. Additional chemotherapy following surgery results in an average five-year survival gain of approximately 4%. To date, it remains unclear which patients are at risk of recurrent lung cancer and what the survival benefits of this potentially toxic treatment may be. This dissertation demonstrates that molecular biomarkers targeting angiogenesis have a prognostic value for the risk of recurrent lung cancer. The applicability of new imaging techniques (DCE-MRI, H215O-PET and 18F-PET) in the response evaluation of patients with metastatic lung cancer was also evaluated. These techniques give us more insight into the tumour biology of individual patients and may help to determine the (failure) response of targeted therapeutic interventions at an earlier stage

Effects of exercise prehabilitation and/or rehabilitation on health-related quality of life and fatigue in patients with non-small cell lung cancer undergoing surgery:A systematic review

Background: This systematic review aimed to appraise the current available evidence regarding the effects of exercise prehabilitation and rehabilitation on perceived health-related quality of life (HRQoL) and fatigue in patients undergoing surgery for non-small cell lung cancer (NSCLC). Methods: Studies were selected according to Cochrane guidelines and assessed for methodological quality and therapeutic quality (the international CONsensus on Therapeutic Exercise aNd Training (i-CONTENT)). Eligible studies included patients with NSCLC performing exercise prehabilitation and/or rehabilitation and postoperative HRQoL and fatigue up to 90-days postoperatively. Results: Thirteen studies were included. Exercise prehabilitation and rehabilitation significantly improved postoperative HRQoL in almost half of the studies (47%), although none of the studies demonstrated a decrease in fatigue. Methodological quality and therapeutic quality were poor in respectively 62% and 69% of the studies. Conclusion: There was an inconsistent effect of exercise prehabilitation and exercise rehabilitation on improving HRQoL in patients with NSCLC undergoing surgery, with no effect on fatigue. Due to the low methodological and therapeutic quality of included studies, it was not possible to identify the most effective training program content to improve HRQoL and reduce fatigue. It is recommended to investigate the impact of a high therapeutic qualified exercise prehabilitation and exercise rehabilitation on HRQoL and fatigue in larger studies

Feasibility of Rehabilitation during Chemoradiotherapy among Patients with Stage III Non-Small Cell Lung Cancer:A Proof-of-Concept Study

Rehabilitation during chemoradiotherapy (CHRT) might (partly) prevent reduction in physical fitness and nutritional status and could improve treatment tolerance in patients with stage III non-small cell lung cancer (NSCLC). The aim of this proof-of-concept study was to investigate the feasibility of a multimodal program for rehabilitation during CHRT. A home-based multimodal rehabilitation program (partly supervised moderate-intensity physical exercise training and nutritional support) during CHRT was developed in collaboration with patients with stage III NSCLC and specialized healthcare professionals. A predetermined number of six patients with stage III NSCLC (aged &gt; 50 years) who underwent CHRT and participated in this program were monitored in detail to assess its feasibility for further development and optimization of the program. The patient's level of physical functioning (e.g., cardiopulmonary exercise test, six-minute walking test, handgrip strength, body mass index, fat free mass index, energy and protein intake) was evaluated in order to provide personalized advice regarding physical exercise training and nutrition. The program appeared feasible and well-tolerated. All six included patients managed to perform the assessments. Exercise session adherence was high in five patients and low in one patient. The performed exercise intensity was lower than prescribed for all patients. Patients were motivated to complete the home-based rehabilitation program during CHRT. Preliminary effects on physical and nutritional parameters revealed relatively stable values throughout CHRT, with inter-individual variation. Supervised and personalized rehabilitation in patients with stage III NSCLC undergoing CHRT seems feasible when the intensity of the physical exercise training was adjusted to the possibilities and preferences of the patients. Future research should investigate the feasibility of a supervised and personalized rehabilitation program during CHRT with a low-to-moderate exercise intensity with the aim to prevent physical decline during CHRT

Patient characteristics.

<p>Patient characteristics.</p

Images of immunohistochemical galectin-1 stainings (A: brown) and galectin-9 stainings (B: brown) of three representative tumors.

<p>Staining was observed in tumor cell compartment (T), stromal compartment (S) and in tumor endothelial cells (arrows). The inset on the left shows the isotype control staining. Scale bar = 50 micrometer. The bar graphs showing quantification of IHC scores for galectin-1 and galectin-9 in different tumor compartments.</p

Multivariate Cox regression analysis with forward selection.

<p>HR = hazard ratio; CI = confidence interval.</p><p>Multivariate Cox regression analysis with forward selection.</p

Galectin mRNA expression profile in tumor tissues obtained from early stage non-small cell lung cancer patients (n- = 87) (A).

<p>The inset shows the expression of the three galectin-9 splice variants. (B) Images of immunohistochemical staining of the galectins with detectable mRNA expression in NSCLC <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107988#pone.0107988-Uhlen1" target="_blank">[27]</a>. (C) Western blot analysis of galectin-9 isoform expression in NSCLC tumor tissue from 5 different patients. Three bands at expected molecular weights of galectin-9FL, galectin-9Δ5 and galectin-9Δ5/6 were observed at varying intensities.</p