Serum markers in small cell lung cancer: Opportunities for improvement

Harmsma, Marjan; Schütte, B.; Ramaekers, Frans C.S.

doi:10.1016/j.bbcan.2013.06.002

Cited by 53 publications

(62 citation statements)

References 228 publications

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“…As an important prognostic factor for SCLC patients, many researches have revealed the association between elevated LDH levels at baseline and poor survival (9,12). In the present study, patients who had an abnormally elevated baseline LDH were observed to have a 1.92-fold risk of death than those with normal LDH (95% CI, 1.29-2.86).…”

Section: Discussionmentioning

confidence: 51%

Modeling the relationship between baseline lactate dehydrogenase and prognosis in patients with extensive-disease small cell lung cancer: a retrospective cohort study

et al. 2018

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Background: Elevated pretreatment lactate dehydrogenase (LDH) has been reported to be associated with poor survival in small cell lung cancer (SCLC). The present study aimed to investigate the continuous relationship between baseline LDH level and survival in patients with extensive-disease SCLC (ED-SCLC). Results: A total of 132 eligible ED-SCLC patients were analyzed. Elevated LDH at baseline was associated with poor survival (HR =1.92; 95% CI,). An increment of LDH would still raise the risk of death even in abnormal range. Among patients with elevated LDH, those who had relatively higher LDH levels (>370 U/L) would have a poorer prognosis than those with moderately elevated LDH levels (245-370 U/L; median survival time, 114 vs. 274 days; P value of log rank test, 0.007).Conclusions: LDH is a significant prognostic biomarker for ED-SCLC patients. The interpretation of continuous relationship between LDH and patients' survival can provide more accurate information for clinical practice. In recent decades, novel approaches of immunotherapy have brought light to cancer treatment (4,5). And trials for investigating the efficacy and safety of immunotherapy with or without chemotherapy in SCLC patients are ongoing (6,7).Predicting prognostic risks of SCLC patients through reliable biomarkers can provide information for disease monitoring and treatment evaluation, which will contribute to the exploration of novel treatments. Lactate dehydrogenase (LDH) is the key enzyme in glycolytic pathway, which is the main source of energy in activities of rapid proliferation and distant metastases for tumor cells. When tissue damage occurs because of tumor activities, LDH will be released from intracellular microenvironment and then lead to an abnormal elevation of serum LDH (8). Therefore, measurements of serum LDH levels can reflect the intensity of tumor activities and thus can be used as a prognostic biomarker. Zhang et al. (9) conducted a metaanalysis involving 4,785 SCLC patients from 28 studies to investigate the prognostic value of baseline LDH for SCLC patients. Their results indicated that patients with an abnormal elevation of serum LDH at baseline would have a 1.45 times higher risk of death than those with normal LDH level (HR =1.45; 95% confidence interval (CI), 1.27-1.66).However, measurements of LDH were all treated as binary outcomes in above studies with a cutoff value at the upper limit of normal range. In that way, it would be impossible to explore the continuous relationship between baseline LDH and survival; namely, different LDH levels within the same group would be regarded as to have the same risk of death.Modeling the relationship between exposure of risk factors and disease outcomes can provide more accurate information for clinical practice. Zhou et al. (10) found nonlinear associations between biomarkers and prognosis in resectable pancreatic ductal adenocarcinoma (PDAC) patients. Their results suggested that a preoperative Carbohydrate antigen 19-9 (CA19-9) level of 100 U/mL and a carcinoembryoni...

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Section: Discussionmentioning

confidence: 51%

Modeling the relationship between baseline lactate dehydrogenase and prognosis in patients with extensive-disease small cell lung cancer: a retrospective cohort study

et al. 2018

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“…GAPDH and 18 S were used as housekeeping genes. The sequence of the primers were as follows: 18 S forward 5Ј-aacccgttgaaccccattcgtgat-3Ј and reverse 5Ј-caggttcacctacggaaaccttgt-3Ј NC_000083.6 (19), GAPDH forward 5Ј-gcattgtggaagggctca and reverse 5Ј-gggtaggaacacggaagg-3Ј NM_ 008084.2; IL-12p40 forward 5Ј-ccactcacatctgctgctgctccacaag-3Ј and reverse 5Ј-acttctcatagtcccttggtccag-3Ј NM_ 008352.2; IFN␥ forward 5Ј-aacgctacacactgcatcttg-3Ј and reverse 5Ј-gacttcaaagagtctgagg-3Ј NM_008337.3; IL-10a forward 5Ј-cgggaagacaataactg-3Ј and reverse 5Ј-catttccgataaggcttgg-3Ј NM_010548; IL-4 forward 5Ј-acaggagaagggacgccat-3Ј and reverse 5Ј-gaagccctacagacgagctca-3Ј NM_021283.2; IL-1b forward 5Ј-caaccaacaagtgatattctccatg-3Ј and reverse 5Ј-gatccacactctccagctgca-3Ј AK156449.1; IL-2 forward 5Ј-cctgagcaggatggagaattaca-3Ј and reverse 5Ј-tccagaacatgccgcafa-3Ј NM_008366.3; FASL forward 5Ј-gaaggaaaccctttcctg-3Ј and reverse 5Ј-ccccggagtatactttg-3Ј NM_001205243.1; FAS forward 5Ј-cacagttaagagttcatactcaaggtactaat-3Ј and reverse 5Ј-caacaaccataggcgatttctgggacttt-3Ј NM_007987.2; TSLP1 forward 5Ј-ctgagagaaatgacggtactcagg-3Ј and reverse 5Ј-gtggtattccttcatgcaatctcc-3Ј NM_021367.2; TSLP2 forward 5Ј-ggcgacagcatggttcttct-3Ј and reverse 5Ј-ttttgtcggggagtgaaggg-3Ј NM_ 021367.2; MCP-1 forward 5Ј-gtgctgaccccaagaaggaa-3Ј and reverse 5Ј-gtgctgaagaccttagggca-3Ј NM_011333.3; TNF␣ forward 5Ј-ggcaggtctactttggagtcattgc-3Ј and reverse 5Ј-acattcgaggctccagtgaattcgg-3Ј NM_013693.2; and IL-8/KC forward 5Ј-cttgaaggtgttgccctcag-3Ј and reverse 5Ј-tggggacaccttttagcatc-3Ј NM_008176.3. Experiments were performed in triplicate.…”

Section: G12dmentioning

confidence: 99%

Inactivation of the Transcription Factor GLI1 Accelerates Pancreatic Cancer Progression

Mills

Zhang²,

Marler

et al. 2014

Journal of Biological Chemistry

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Background: GLI1 is required for pancreatic tumor initiation; however, its role at later stages of carcinogenesis remains elusive. Results: Genetic inactivation of GLI1 accelerates pancreatic cancer progression. Conclusion: GLI1 can act as both a promoter and suppressor of pancreatic carcinogenesis depending on the tumor stage. Significance: This knowledge increases our understanding of pancreatic carcinogenesis and may help the design of therapies targeting GLI1-related pathways.

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“…Tumor markers, including carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCCAg) and cytokeratin-19 fragments (Cyfra21-1), are clinically applied for the early detection of lung cancer (4,5). However, the sensitivity and specificity of these biomarkers are not adequate (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Transthyretin as a potential biomarker for the differential diagnosis between lung cancer and lung infection

et al. 2014

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Abstract. Satisfactory biomarkers for screening and early diagnosis of lung cancer remain scarce and require further investigation. The aim of the present study was to examine the changes of the biochemical and protein composition in the serum and pleural effusion from lung cancer and lung infection (bacterial pneumonia) patients. A total of 92 patients with lung cancer, 38 with bacterial pneumonia and 42 healthy controls were enrolled in the study. The serum levels of cholesterol, apolipoprotein A and transthyretin (TTR) in the lung cancer patients were higher than that of the lung infection patients (P<0.05). The levels of TTR were higher, whereas the activity of adenosine deaminase (ADA) was lower in the pleural effusion from the lung cancer patients compared to the lung infection patients (P<0.05). Furthermore, the pleural effusion/serum TTR ratios in the lung cancer patients were higher, whereas the ratios of ADA were lower (P<0.05). By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, four major peaks corresponding to native TTR, Sul-TTR, Cys-TTR and Cysgly-TTR were observed in the serum of the lung cancer and lung infection patients. A significant increase was found in the proportion of Cysgly-TTR in the pleural effusion from the patients with lung cancer. The data indicated that a combination of pleural effusion/serum TTR ratios and modified TTR may be beneficial for the differential diagnosis between lung cancer and lung infection. IntroductionLung cancer is one of the most common malignant tumors worldwide, with a 5-year survival rate of 14% (1). Thus far, the statistics for cancer occurrence and outcome show that lung cancer remains a primary cause of mortality from cancer (2,3). Since the incidence and mortality of lung cancer increases significantly every year, it represents a major economic burden to society. Currently, the screening and early diagnosis of lung cancer in clinics relies mainly on magnetic resonance imaging (MRI) and computed tomography (CT) imaging, whereas the final diagnosis is established on the basis of histopathological examination results. The early clinical manifestations of lung cancer patients are relatively mild and not typical, easily overlooked or confused with benign inflammatory disease, such as lung infection. Therefore, early identification and diagnosis of lung cancer is significant since lung cancer may be curable in its early stages (1).Thus far, increasing attention has focused on searching for improved biomarkers that function not only to detect lung cancer at an early stage but also to explore the molecular mechanisms that underlie cancer development. Tumor markers, including carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCCAg) and cytokeratin-19 fragments (Cyfra21-1), are clinically applied for the early detection of lung cancer (4,5). However, the sensitivity and specificity of these biomarkers are not adequate (6-8). Combined detection usi...

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Serum markers in small cell lung cancer: Opportunities for improvement

Cited by 53 publications

References 228 publications

Modeling the relationship between baseline lactate dehydrogenase and prognosis in patients with extensive-disease small cell lung cancer: a retrospective cohort study

Modeling the relationship between baseline lactate dehydrogenase and prognosis in patients with extensive-disease small cell lung cancer: a retrospective cohort study

Inactivation of the Transcription Factor GLI1 Accelerates Pancreatic Cancer Progression

Transthyretin as a potential biomarker for the differential diagnosis between lung cancer and lung infection

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