Serum LAMC2 enhances the prognostic value of a multi-parametric panel in non-small cell lung cancer

Korbakis, Dimitrios; Dimitromanolakis, Apostolos; Prassas, Ioannis; Davis, Gerard; Barber, E.L.; Reckamp, Karen L.; Blasutig, Ivan M.; Diamandis, Eleftherios P.

doi:10.1038/bjc.2015.171

Cited by 29 publications

(26 citation statements)

References 62 publications

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“…Protein markers, for instance serum cytokeratin 19 fragments (CYFRA 21-1), have been investigated recently in patients with advanced LADC [ 1 ]. Other examples are carcinoembryonic antigen (CEA) [ 2 ], serum amyloid A (SAA) [ 3 , 4 ], cancer antigen 125 (CA 125) [ 2 , 5 ], haptoglobin-alpha 2 (HAP2) [ 6 , 7 ], apolipoprotein A1 (ApoA1) [ 6 , 8 ], kallikreins (KLKs) [ 9 - 11 ], laminin C2 (lamC2) [ 5 ] and plasma fibrinogen [ 12 ]. The analysis of other circulating tumor-derived biomarkers like cell-free nucleic acids (such as DNA and microRNAs [ 13 ]), metabolites [ 14 , 15 ] or circulating tumor cells (CTCs) [ 13 , 16 , 17 ] might also hold potential in predicting clinical outcome.…”

Section: Introductionmentioning

confidence: 99%

High circulating activin A level is associated with tumor progression and predicts poor prognosis in lung adenocarcinoma

et al. 2016

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Activin A (ActA)/follistatin (FST) signaling has been shown to be deregulated in different tumor types including lung adenocarcinoma (LADC). Here, we report that serum ActA protein levels are significantly elevated in LADC patients (n=64) as compared to controls (n=46, p=0.015). ActA levels also correlated with more advanced disease stage (p<0.0001) and T (p=0.0035) and N (p=0.0002) factors. M1 patients had significantly higher ActA levels than M0 patients (p<0.001). High serum ActA level was associated with poor overall survival (p<0.0001) and was confirmed as an independent prognostic factor (p=0.004). Serum FST levels were increased only in female LADC patients (vs. female controls, p=0.031). Two out of five LADC cell lines secreted biologically active ActA, while FST was produced in all of them. Transcripts of both type I and II ActA receptors were detected in all five LADC cell lines. In conclusion, our study does not only suggest that measuring blood ActA levels in LADC patients might improve the prediction of prognosis, but also indicates that this parameter might be a novel non-invasive biomarker for identifying LADC patients with organ metastases.

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Section: Introductionmentioning

confidence: 99%

High circulating activin A level is associated with tumor progression and predicts poor prognosis in lung adenocarcinoma

et al. 2016

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“…Although serum CRP and SCC-Ag levels have been reported to predict postoperative recurrence, progression, and prognosis in PSCC, [13][14][15] their prognostic values need to be validated by large-scale investigations. In previous reports, elevated expression of LAMC2 was detected in numerous malignancies, [17][18][19] and cytoplasmic accumulation of LAMC2 and/or an increase in serum LAMC2 was correlated with tumor metastasis and poor prognosis in patients. 12,18,19 Here, we found that LAMC2 expression was upregulated, LAMC2 demonstrated an especially high cytoplasmic accumulation in PSCC tissues, and that LAMC2 overexpression was associated with LN metastasis in PSCC.…”

Section: Discussionmentioning

confidence: 91%

“…In previous reports, elevated expression of LAMC2 was detected in numerous malignancies, [17][18][19] and cytoplasmic accumulation of LAMC2 and/or an increase in serum LAMC2 was correlated with tumor metastasis and poor prognosis in patients. 12,18,19 Here, we found that LAMC2 expression was upregulated, LAMC2 demonstrated an especially high cytoplasmic accumulation in PSCC tissues, and that LAMC2 overexpression was associated with LN metastasis in PSCC. Furthermore, sLAMC2 level was associated with N stage and pathologic grade in the analyzed patients.…”

Section: Discussionmentioning

confidence: 91%

“…Together with laminin alpha 3 and laminin beta 3, laminin gamma 2 (LAMC2) composes the heterotrimeric basement membrane component laminin 332 and plays important physiologic and pathologic roles through its involvement in cellular migration and adhesion, especially in the processes of tumor invasion and metastasis. 16 It has been reported that the overexpression of LAMC2 is associated with a poor prognosis in numerous cancers, [17][18][19] and cytoplasmic accumulation of LAMC2, as opposed to its extracellular deposition in the basement membrane, is correlated with cancer metastasis and poor prognosis. 18 Interestingly, elevated LAMC2 levels have also been detected in peripheral blood, indicating that LAMC2 could be a novel cancer biomarker.…”

Section: Introductionmentioning

confidence: 99%

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Elevated serum LAMC2 is associated with lymph node metastasis and predicts poor prognosis in penile squamous cell carcinoma

Zhou

Deng

Chen

et al. 2018

CMAR

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PurposeMolecular biomarkers, especially serologic factors, have been widely applied in cancer diagnosis and patient follow-up. However, there are few valuable prognostic factors in penile squamous cell carcinoma (PSCC). Here, the authors investigated whether laminin gamma 2 (LAMC2) expression, especially serum LAMC2 (sLAMC2) level, was a suitable prognostic factor that could aid in the prediction of survival in PSCC.Patients and methodsThis study included 114 PSCC patients. Reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect LAMC2 expression; enzyme-linked immunosorbent assays were used to test sLAMC2 concentration; and a Transwell assay and an in vivo experiment in nude mice were used to test PSCC cell migration, invasion, and metastasis. The chi-squared test was used to analyze the association between LAMC2 level and clinical parameters, the Cox proportional hazards regression model was used to evaluate the hazard ratio for death, and Kaplan–Meier analysis with a log-rank test was used for the survival analysis.ResultsLAMC2 was overexpressed in PSCC tissues, and the LAMC2 expression level was higher in metastatic lymph node (LN) tissues than in primary cancer tissues; moreover, the LAMC2 levels in primary cancer tissues and sLAMC2 were higher in patients with LN metastasis than in those without LN metastasis. Upregulated LAMC2 facilitated the migration, invasion, and epithelial-to-mesenchymal transition of PSCC cells in vitro and promoted LN metastasis of PSCC cells in nude mice. Elevated LAMC2 levels were strongly correlated with advanced clinicopathologic parameters, especially LN metastasis, in PSCC patients and predicted shorter disease-specific survival. The predictive value of sLAMC2 is superior to that of C-reactive protein and squamous cell carcinoma antigen previously reported in PSCC patients, and a stratification analysis revealed that the level of sLAMC2 had a higher predictive value for disease-specific survival in early penile cancer (especially at the N0/X stage) than in later-stage penile cancer.ConclusionThese findings suggest that sLAMC2 is a potential serologic prognostic marker in PSCC and could aid in risk stratification in early-stage PSCC patients.

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“…Wikoff WR et al applied a liquid chromatography/mass spectrometry hydrophilic interaction method to analyze a wide rage of serum metabolites, and identified diacetylspermine was a novel serum metabolite with obvious performance in prediagnostic NSCLC [21]. From the clinical investigator's standpoint, CA125, CEA, CYFRA21-1 and SCC still play as the leading serum biomarker in NSCLC and are mainly applied in disease monitoring[17]. Therefore, novel biomarker for diagnosis and prognosis evaluation would assist the doctors to improve the clinical management of NSCLC.…”

Section: Discussionmentioning

confidence: 99%

High serum haptoglobin level is associated with tumor progression and predicts poor prognosis in non-small cell lung cancer

Wang

Yan

et al. 2016

Oncotarget

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The overall survival time of non-small cell lung cancer (NSCLC) has not improved dramatically in recent decades. An important reason is the lacking of valuable biomarkers. Haptoglobin was reported to have activities of anti-inflammatory, anti-oxidant, autoimmune and tumor angiogenesis. However its potential role as a tumor biomarker was not well recognized. We used an immunoturbidimetry method to measure serum haptoglobin levels in 205 NSCLC patients, and 210 normal healthy controls. We found that serum haptoglobin levels were significantly elevated in NSCLC patients compared with normal healthy controls (1.985±1.039 mg/mLvs. 0.922 ± 0.495 mg/mL, respectively, P < 0.0001). Higher serum haptoglobin levels were associated with advanced TNM stage, lymph node metastasis, and distant metastasis. Area under receiver operating characteristic curve (ROC) for serum haptoglobin was 0.809 (95% CI: 0.767–0.852) at a specificity of 0.881 and sensitivity of 0.639. The optimal cut-off value of haptoglobin was 1.495 mg/mL for discriminating NSCLC from normal healthy controls. Kaplan-Meier log rank analysis revealed that the higher serum haptoglobin levels group had a poorer overall survival compared with lower haptoglobin group (the median survival was 12.0 weeks, 26.0 weeks, respectively, P < 0.01). Further univariate and multivariate Cox regression analysis showed that serum haptoglobin was an independent risk factor of prognosis of NSCLC patients (P < 0.01, P = 0.01, respectively). In conclusion, our study suggests that serum haptoglobin may act as useful clinical serological biomarkers in progression and prognostic evaluation in NSCLC.

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Serum LAMC2 enhances the prognostic value of a multi-parametric panel in non-small cell lung cancer

Cited by 29 publications

References 62 publications

High circulating activin A level is associated with tumor progression and predicts poor prognosis in lung adenocarcinoma

High circulating activin A level is associated with tumor progression and predicts poor prognosis in lung adenocarcinoma

Elevated serum LAMC2 is associated with lymph node metastasis and predicts poor prognosis in penile squamous cell carcinoma

High serum haptoglobin level is associated with tumor progression and predicts poor prognosis in non-small cell lung cancer

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