Distant Metastasis Risk Definition by Tumor Biomarkers Integrated Nomogram Approach for Locally Advanced Nasopharyngeal Carcinoma

Identifying metastasis remains a challenge for death control and tailored therapy for nasopharyngeal carcinoma (NPC). Here, we addressed this by designing a nomogram-based Cox proportional regression model through integrating a panel of tumor biomarkers. A total of 147 locally patients with advanced NPC, derived from a randomized phase III clinical trial, were enrolled. We constructed the model by selecting the variables from 31 tumor biomarkers, including 6 pathological signaling pathway molecules and 3 Epstein-Barr virus-related serological variables. Through the least absolute shrinkage and selection operator (LASSO) Cox proportional regression analysis, a nomogram was designed to refine the metastasis risk of each NPC individuals. Using the LASSO Cox regression model, we constructed a 9 biomarkers-based prognostic nomogram: Beclin 1, Aurora-A, Cyclin D1, Ki-67, P27, Bcl-2, MMP-9, 14-3-3σ, and VCA-IgA. The time-dependence receiver operating characteristic analysis at 1, 3, and 5 years showed an appealing prognostic accuracy with the area under the curve of 0.830, 0.827, and 0.817, respectively. In the validation subset, the concordance index of this nomogram reached to 0.64 to identify the individual metastasis pattern. Supporting by this nomogram algorithm, the individual metastasis risk might be refined personally and potentially guiding the treatment decisions and target therapy against the related signaling pathways for patients with locally advanced NPC.

[1]  K. Lam,et al.  Management of Nasopharyngeal Carcinoma: Is Adjuvant Therapy Needed? , 2018, Journal of oncology practice.

[2]  Christine Y. Lu,et al.  Survival outcomes for Australian women receiving trastuzumab for HER2-positive metastatic breast cancer following (neo)adjuvant trastuzumab: a national population-based observational study (2006–2014) , 2017, British Journal of Cancer.

[3]  T. Gamblin,et al.  The prognostic utility of baseline alpha‐fetoprotein for hepatocellular carcinoma patients , 2017, Journal of surgical oncology.

[4]  Ji-Jin Yao,et al.  Prognostic value of serum Epstein–Barr virus antibodies in patients with nasopharyngeal carcinoma and undetectable pretreatment Epstein–Barr virus DNA , 2017, Cancer science.

[5]  Mingyu Liu,et al.  Overexpression of N-cadherin and β-catenin correlates with poor prognosis in patients with nasopharyngeal carcinoma. , 2017, Oncology letters.

[6]  J. Griggs,et al.  Use of CA-125 Tests and Computed Tomographic Scans for Surveillance in Ovarian Cancer. , 2016, JAMA oncology.

[7]  Xinran Tang,et al.  Microarray Expression Profiling of Long Non-Coding RNAs Involved in Nasopharyngeal Carcinoma Metastasis , 2016, International journal of molecular sciences.

[8]  Rui Sun,et al.  Establishment and Validation of Prognostic Nomograms for Endemic Nasopharyngeal Carcinoma. , 2016, Journal of the National Cancer Institute.

[9]  Anne W M Lee,et al.  Management of Nasopharyngeal Carcinoma: Current Practice and Future Perspective. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  C. Qian,et al.  Ten-year outcomes of a randomised trial for locoregionally advanced nasopharyngeal carcinoma: A single-institution experience from an endemic area. , 2015, European journal of cancer.

[11]  D. Kannarunimit,et al.  A randomized phase II/III study of adverse events between sequential (SEQ) versus simultaneous integrated boost (SIB) intensity modulated radiation therapy (IMRT) in nasopharyngeal carcinoma; preliminary result on acute adverse events , 2015, Radiation Oncology.

[12]  Li Zhang,et al.  Development and validation of a nomogram for predicting survival in patients with resected non-small-cell lung cancer. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  J. Baselga,et al.  Biomarker analyses in CLEOPATRA: a phase III, placebo-controlled study of pertuzumab in human epidermal growth factor receptor 2-positive, first-line metastatic breast cancer. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  Rensheng Wang,et al.  Concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: treatment outcomes of a prospective, multicentric clinical study. , 2014, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[15]  H. Ying,et al.  A phase III randomized study comparing neoadjuvant chemotherapy with concurrent chemotherapy combined with radiotherapy for locoregionally advanced nasopharyngeal carcinoma: updated long-term survival outcomes. , 2014, Oral oncology.

[16]  Jian Lu,et al.  Prognostic and predictive value of a microRNA signature in stage II colon cancer: a microRNA expression analysis. , 2013, The Lancet. Oncology.

[17]  E. Hui,et al.  Targeting tumor hypoxia in nasopharyngeal carcinoma , 2013, Head & neck.

[18]  R. Sun,et al.  A randomized trial of induction chemotherapy plus concurrent chemoradiotherapy versus induction chemotherapy plus radiotherapy for locoregionally advanced nasopharyngeal carcinoma. , 2012, Oral oncology.

[19]  Jie Xu,et al.  Aurora‐A activation, correlated with hypoxia‐inducible factor‐1α, promotes radiochemoresistance and predicts poor outcome for nasopharyngeal carcinoma , 2012, Cancer science.

[20]  Jin-Ching Lin,et al.  Current management of nasopharyngeal cancer. , 2012, Seminars in radiation oncology.

[21]  A. King,et al.  A phase II study of concurrent cetuximab-cisplatin and intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma. , 2012 .

[22]  Y. Huang,et al.  Epithelial–mesenchymal transition biomarkers and support vector machine guided model in preoperatively predicting regional lymph node metastasis for rectal cancer , 2012, British Journal of Cancer.

[23]  Yan Zhang,et al.  Molecular Prognostic Prediction for Locally Advanced Nasopharyngeal Carcinoma by Support Vector Machine Integrated Approach , 2012, PloS one.

[24]  A. Garden,et al.  Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): a phase 2 multi-institutional trial. , 2012, The Lancet. Oncology.

[25]  Jie Xu,et al.  Serologic antienzyme rate of Epstein-Barr virus DNase-specific neutralizing antibody segregates TNM classification in nasopharyngeal carcinoma. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  Jie Xu,et al.  Elevated Beclin 1 expression is correlated with HIF-1α in predicting poor prognosis of nasopharyngeal carcinoma , 2010, Autophagy.

[27]  Jian-ming Li,et al.  Over-expression of Nanog predicts tumor progression and poor prognosis in colorectal cancer , 2010, Cancer biology & therapy.

[28]  Jordi Giralt,et al.  Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. , 2010, The Lancet. Oncology.

[29]  Jun Ma,et al.  Long-term survival after cisplatin-based induction chemotherapy and radiotherapy for nasopharyngeal carcinoma: A pooled data analysis of two phase III trials. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  O. Kallioniemi,et al.  Tissue microarrays (TMAs) for high‐throughput molecular pathology research , 2001, International journal of cancer.

[31]  Jun Ma,et al.  A comparison of the Chinese 1992 and fifth‐edition International Union Against Cancer staging systems for staging nasopharyngeal carcinoma , 2000, Cancer.

[32]  W. Enker,et al.  Combined modality therapy of rectal cancer: decreased acute toxicity with the preoperative approach. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[33]  Pelayo Vilar,et al.  Nasopharyngeal Carcinoma , 1966 .