Differences in LC3B expression and prognostic implications in oropharyngeal and oral cavity squamous cell carcinoma patients.

BACKGROUND: This study examined the prognostic significance of microtubule-associated protein light chain 3B (LC3B) expression in oropharyngeal and oral cavity squamous cell carcinoma (SCC). The prognostic significance of LC3B expression in relation to human papillomavirus (HPV) status in oropharyngeal SCC was also examined. METHODS: Tissue microarrays (TMAs) were constructed from formalin-fixed, paraffin-embedded oropharyngeal (n = 47) and oral cavity (n = 95) SCC tissue blocks from patients with long-term recurrence and overall survival data (median = 47 months). LC3B expression on tumour was assessed by immunohistochemistry and evaluated for associations with clinicopathological variables. LC3B expression was stratified into high and low expression cohorts using ROC curves with Manhattan distance minimisation, followed by Kaplan-Meier and multivariable survival analyses. Interaction terms between HPV status and LC3B expression in oropharyngeal SCC patients were also examined by joint-effects and stratified analyses. RESULTS: Kaplan-Meier survival and univariate analyses revealed that high LC3B expression was correlated with poor overall survival in oropharyngeal SCC patients (p = 0.007 and HR = 3.18, 95% CI 1.31-7.71, p = 0.01 respectively). High LC3B expression was also an independent prognostic factor for poor overall survival in oropharyngeal SCC patients (HR = 4.02, 95% CI 1.38-11.47, p = 0.011). In contrast, in oral cavity SCC, only disease-free survival remained statistically significant after univariate analysis (HR = 2.36, 95% CI 1.19-4.67, p = 0.014), although Kaplan-Meier survival analysis showed that high LC3B expression correlated with poor overall and disease-free survival (p = 0.046 and 0.011 respectively). Furthermore, oropharyngeal SCC patients with HPV-negative/high LC3B expression were correlated with poor overall survival in both joint-effects and stratified presentations (p = 0.024 and 0.032 respectively). CONCLUSIONS: High LC3B expression correlates with poor prognosis in oropharyngeal and oral cavity SCC, which highlights the importance of autophagy in these malignancies. High LC3B expression appears to be an independent prognostic marker for oropharyngeal SCC but not for oral cavity SCC patients. The difference in the prognostic significance of LC3B between oropharyngeal and oral cavity SCCs further supports the biological differences between these malignancies. The possibility that oropharyngeal SCC patients with negative HPV status and high LC3B expression were at particular risk of a poor outcome warrants further investigation in prospective studies with larger numbers.

New frontiers in circulating tumor cell analysis: A reference guide for biomolecular profiling toward translational clinical use.

Circulating tumor cells (CTCs) are now routinely isolated from blood, and measurement of CTC concentrations appears to correlate well with survival in patients with cancer. Interrogation of the molecular profile of CTCs for expression of protein biomarkers, genetic variants and gene expression provides opportunities to use this information to guide personalized treatment, monitor therapy and detect emerging resistance. However, successful application of profiling techniques requires analyses that deliver a reliable and clinically relevant representation of a patient's cancer as it changes with time. Here, we comprehensively review the current knowledge of therapeutically relevant biomarkers in isolated CTCs obtained by fluorescence imaging and genomic profiling approaches. The reviewed data support the notion that molecular profiling of CTCs will provide a reliable representation or surrogate index of tumor burden. Large-scale translational trials, many currently in progress, will provide critical data to progress CTC analysis toward wider clinical use in personalized treatment.

Silencing the mannose 6-phosphate/IGF-II receptor differentially affects tumorigenic properties of normal breast epithelial cells.

Although loss of the mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF-IIR) in breast cancer is believed to play a role in tumorigenesis, it has not been demonstrated that M6P/IGF-IIR loss is sufficient to confer a malignant phenotype in an untransformed cell. We investigated the impact of M6P/IGF-IIR silencing using phenotypically normal (MCF-10A) and oncogenically transformed (MCF-10T, the c-Ha-ras transformed derivative of MCF-10A) human breast epithelial cell lines as model systems. In both cell lines, silencing of M6P/IGF-IIR increased cell proliferation and motility, with the effects being more pronounced in MCF-10A cells. Although anchorage-independent growth was increased by M6P/IGF-IIR silencing in MCF-10T cells, MCF-10A cells did not acquire the ability to grow in soft agar. Conversely, reduced M6P/IGF-IIR expression increased the invasive potential of MCF-10A cells, but did not enhance the already high rate of invasion of MCF-10T cells. M6P/IGF-IIR silencing had no effect on basal or IGF-II-stimulated IGF-I receptor (IGF-IR) or AKT phosphorylation in either cell line, but both were abrogated by IGF-IR kinase inhibition, which also reduced the stimulatory effect of M6P/IGF-IIR silencing on proliferation under basal and IGF-II-stimulated conditions in both cell lines. However, cell motility was neither stimulated by IGF-II nor reduced by IGF-IR inhibition, suggesting that potentiation of specific tumorigenic features in response to M6P/IGF-IIR silencing involves IGF-II- dependent and -independent mechanisms. Collectively, these data suggest that M6P/IGF-IIR silencing alone is insufficient to confer a tumorigenic phenotype, but can enhance tumorigenicity in an already transformed cell.

Elevated levels of soluble PD-L1 are associated with reduced recurrence in papillary thyroid cancer.

To date, no research evaluating the predictive capabilities of soluble programmed cell death-ligand 1 (sPD-L1) in thyroid cancer patients has been performed. We aimed to investigate the prognostic significance of sPD-L1 expression in papillary thyroid cancer (PTC) and to evaluate the association between sPD-L1 levels with tumoural PD-L1 expression and patient outcomes. Pre-treatment levels of serum and plasma sPD-L1 were measured by ELISA in 101 PTC patients. Tissue microarrays were stained with an anti-PD-L1 antibody, clone SP263 (Ventana). The median serum sPD-L1 concentration in PTC patients was significantly higher compared to healthy controls (P = 0.028). An increased incidence of extrathyroidal extension was significantly associated with an elevated serum sPD-L1 level (P = 0.015). Patients with high serum sPD-L1 levels had significantly shorter median disease-free survival (DFS) as compared to those with low sPD-L1 levels (P = 0.011). Following multivariate analysis, serum sPD-L1 was the only statistically significant predictor for DFS. Patients with both positive serum and tumoural PD-L1 expression had a significantly shorter DFS than those in any other subgroup (P = 0.007). Our study is the first to confirm that sPD-L1 concentration is significantly associated with patient outcome in PTC. Soluble PD-L1 may provide clinicians with a non-invasive biomarker that can lessen dependence on tissue biopsies and diagnose aggressive thyroid cancers at a more treatable stage.

Health professionals' opinions on supporting a cancer biobank: identification of barriers to combat biobanking pitfalls.

Although rarely acknowledged, a successful biobank is highly dependent on the support of the health professionals who assist the biobank in all aspects of its activities. In many cases, the lack of health professional support can be a limiting factor in the biobanking process of collecting and processing high-quality biospecimens. The aim of this study was to determine the attitudes of health professionals towards cancer biobanking. Using a 5-point Likert scale questionnaire, important aspects of biobanking, including accrual, quality, knowledge, responsiveness, impact, access, trust, governance and accreditation, were investigated. In total, 95 of 124 health and medical practitioners who were approached participated in this study (77% response rate). Health professionals in general supported the aims of biobanking with 56% of participants showing willingness to create a biobank and recruit donors (accrual), 85% understanding the importance in the storage and distribution of biospecimens (quality), 88% having an appreciation for the role of a biobank in furthering cancer research (knowledge), 70% showing awareness of the use of biospecimens in future research initiatives (responsiveness) and 73% demonstrating support for a biobank with proper control, authority and credibility measures in place (governance and accreditation). Overall, provided that proper information about the activities of the biobank and researcher access was transparent, health professionals were very willing to support cancer biobanking. These findings may assist in developing strategies for the establishment and maintenance of biobanks and aid the implementation of more effective policies and procedures to embed biobanking into routine hospital practices.

Predictive and prognostic value of circulating tumor cell detection in lung cancer: a clinician's perspective.

There is increasing evidence for the use of circulating tumor cells (CTCs) as a "liquid biopsy" for early detection of lung cancer recurrence, prognosticating disease and monitoring treatment response. Further, CTC molecular analysis and interrogation of single cells hold significant potential in providing insights into tumor biology and the metastatic process. Ongoing research will likely see the translation of CTCs as a prognostic and predictive biomarker in both small cell, and non-small cell, lung cancer to routine clinical practice.