The Hunt for Biomarkers: Fibrinogen Levels and Mesothelioma



MCA Staff Writers

Presenting Up-to-Date Mesothelioma Topics



Cancer patients and physicians often face the question, "Will this treatment benefit this individual patient?" Scientists prefer to answer this question by measuring a biomarker in the blood, urine or tumor tissue from the patient. Biomarkers: what, when, and why

As a review, all cancers express some molecules differently than normal cells. A biomarker usually is a molecule that is found only in patients with a specific disease, such as lung cancer or mesothelioma. Alternatively, a biomarker can be the loss of a specific molecule found in normal cells or it may be a mutated protein. While some biomarkers are found only on the tissue, biomarkers are easier to monitor if they can be measured in the blood or urine of a patient. Some biomarkers help identify people with early cancer. Other biomarkers help predict which group of patients can benefit the most from a specific treatment. Fibrinogen: a potential biomarker for lung cancer

In honor of May being Cancer Research Month, we'll describe the promising role of fibrinogen as a biomarker. Fibrinogen is a large protein coated with sugars (glycoprotein, 340kDa) in the blood. During an injury, fibrinogen is cleaved by clotting factors to make fibrin. Fibrin is laid down over the wound and forms an essential part of the clot. The advantage of fibrinogen as a marker is that the patients' fibrinogen levels are routinely taken before treatment. Abnormal fibrinogen levels can suggest a clotting disorder or an acute infection: important information for the treating physicians.

Some non-small cell lung cancer (NSCLC) patients have high levels of fibrinogen (>4400 mg/L) in their blood before therapy. The fibrinogen levels were monitored in all patients with lung cancer in the study 1. Patients with high fibrinogen (hyperfibrinogenemia) had a higher risk of their tumor growing rapidly and death 1, 2. After chemotherapy, the fibrinogen levels declined in 61% of patients (who originally had high levels of it). Zhao suggests, "reduction of plasma fibrinogen levels is as promising a biomarker as CEA and CA125" to monitor the effectiveness of chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. Research continues on developing fibrinogen as a biomarker for monitoring cancer progression and response of lung cancer to treatment. Fibrinogen: potential biomarker for response to multimodality therapy of mesothelioma

Fibrinogen also is potentially a useful biomarker in patients with mesothelioma. Most patients with mesothelioma have higher levels of fibrinogen than normal patients (150 mg/dL to 300 mg/dL). In Ghanim et al.'s retrospective study 3, mesothelioma patients with fibrinogen levels less than 627 mg/dL had significantly longer survival times compared to mesothelioma patients with fibrinogen levels at 628mg/dL or greater. Some patients received surgery, chemotherapy and radiotherapy whereas other patients chose chemotherapy and radiotherapy but no surgery.

Multivariate analysis calculated which variables were associated with longer survival. The authors chose to regroup the patients based on the fibrinogen level found in 75% of mesothelioma patients (at or less than 750mg/dL). Ghanim et al 3 found that the group of mesothelioma patients with fibrinogen levels at 750 mg/dL or below showed significantly longer survival (median of 31 months) if they received all three treatments- surgery, chemotherapy, and radiation than those who only received chemotherapy and radiotherapy (13.8 month). In contrast, the group of patients with fibrinogen levels above 750 mg/dL did not benefit from the surgery and had a median overall survival of 5.1 months. In this study, the fibrinogen level of 750 mg/dL had a sensitivity of 31.3% and a specificity of 82.9%.

The use of fibrinogen as a predictor of overall survival or response to the multimodality therapy (surgery, chemotherapy and radiation) in mesothelioma patients is under development.

--- Sheng L, Luo M, Sun X, Lin N, Mao W, Su D. Serum fibrinogen is an independent prognostic factor in operable nonsmall cell lung cancer. Int J Cancer 2013;133(11):2720-2725. Zhao J, Zhao M, Jin B et al. Tumor response and survival in patients with advanced non-small-cell lung cancer: the predictive value of chemotherapy-induced changes in fibrinogen. BMC Cancer 2012;12330. Ghanim B, Hoda MA, Klikovits T et al. Circulating fibrinogen is a prognostic and predictive biomarker in malignant pleural mesothelioma. Br J Cancer 2014;110(4):984-990.

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Conroy offers to be witness in NBN contractor dispute





Speaking to a Senate hearing on the NBN in Sydney, Mr Conroy said he had offered to be a witness for the Tasmanian subcontractors in the court case as the communications minister serving when Visionstream was signed on. Photo: Louise Kennerley

David Ramli

Senior Labor Senator Stephen Conroy has volunteered to be a witness in a looming court stoush between contractors building the national broadband network - a rare move for a former government minister and serving Senator.

Six Tasmanian contractors travelled to Sydney on Friday to seek legal advice on whether they could sue NBN Co contractor Visionstream over allegations it broke contractual agreements to provide work building the national broadband network.

Work across the state came to a standstill in late 2013 after Visionstream stopped significant rollout work citing issues including asbestos mishandling, work has since gradually increased.

The subcontractors claim they missed out on millions of dollars of work after Visionstream reneged on contractual agreements despite investing in training and equipment for the rollout.

Speaking to a Senate hearing on the NBN in Sydney, Mr Conroy said he had offered to be a witness for the Tasmanian subcontractors in the court case as the communications minister serving when Visionstream was signed on.

Mr Conroy's spokesperson has confirmed his offer was genuine.

The Opposition is keen to slam the government over what it perceives as a slowdown in work across the country.

It sees the NBN slowdown in Tasmania as being a symptom of the Coalition's change in rollout technology from fibre-to-the-premise to fibre-to-the-node, which is cheaper and faster to roll out but provides slower internet speeds. READ NEXT:

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Emmerdale's Verity Rushworth says Donna story gets darker





Verity Rushworth says Donna's storyline to get darker.REX/Steve Meddl Emmerdale actress Verity Rushworth has said her character Donna's storyline will get "bigger and darker".

Donna has returned to the village as she is terminally ill and only has a few months to live.

Rhona Goskirk (Zoe Henry) is the only person in the village that knows the truth as Donna is reluctant to share her secret.

Rushworth told Daily Star: "It changes gear and spirals into real intense drama. It gets bigger and darker than just Donna being ill. It gets much more thrilling.

"It's kind of to do with her working in the police where she is put in a situation. I can't say much more but viewers will love it."

The actress revealed that she was inspired by former Coronation Street actress Julie Hesmondhalgh following her portrayal of Hayley Cropper's terminal cancer storyline.

Rushworth said: "Julie had to lose a lot of weight and I know that's one of the symptoms of Donna's rare lung cancer, mesothelioma, so I am thinking about that too. It won't be easy now I am back eating my mum's Yorkshire puddings!

"We don't know yet whether Donna will die on screen though, but Julie definitely inspired me to do this well."

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