Histone deacetylase 6 expression in metastatic lymph nodes is a valuable prognostic marker for resected node-positive esophageal squamous cell cancer
CANCER MANAGEMENT AND RESEARCH
Authors: Xie, Xuan; Luo, Kongjia; Li, Yi; Ling, Yihong; Zhang, Shuishen; Xie, Xiuying; Wen, Jing
Abstract
Background: Histone deacetylase 6 (HDAC6) exerts enzymatic deacetylation activity on histones and on non-histone substrates and plays a key role in microtubule dynamics and chaperone activities. In addition, previous studies have demonstrated its role in cancer progression. However, its clinical significance in esophageal squamous cell cancer (ESCC) has not been elucidated. We investigated the correlation of HDAC6 expression and clinical outcome in a group of T3N1-3M0 surgically resected ESCCs. Methods: Tissue microarrays were conducted on 209 surgically resected T3N1-3M0 ESCC tumors, including 163 pairs of primary tumors (PTs) and their corresponding metastatic lymph nodes (MLNs). Immunohistochemistry was utilized to evaluate HDAC6 protein levels. The relationship between patient outcomes and HDAC6 expression was analyzed statistically. Results: The level of HDAC6 expression in ESCC MLNs was found to be significantly lower than that in PTs (P<0.001). Patients with lower MLN HDAC6 expression demonstrated improved overall survival (P=0.011) and disease-free survival (P=0.012) than those with higher HDAC6 expression. HDAC6 expression levels in PTs revealed no prognostic significance. Multivariate analysis showed that the MLN HDAC6 expression level was an independent prognostic factor for both overall survival (HR 1.456, P=0.029) and diseasefree survival (HR 1.432, P=0.033). Conclusion: High expression of HDAC6 in MLNs but not in PTs suggests a poor prognosis for patients with resected T3N1-3M0 ESCC. We should take into account the protein expression of MLNs when assessing prognosis in patients with lymph-node involvement.
Ultra-Sensitive Detection and Inhibition of the Metastasis of Breast Cancer Cells to Adjacent Lymph Nodes and Distant Organs by Using Long-Persistent Luminescence Nanoparticles
ANALYTICAL CHEMISTRY
Authors: Liu, Hanghang; Ren, Feng; Zhou, Xingguo; Ma, Changqiu; Wang, Tingting; Zhang, Hao; Sun, Qiao; Li, Zhen
Abstract
The metastasis of breast cancer mainly occurs through the axillary lymph node and blood circulation systems. It is extremely difficult to know when the cancer cells start to metastasize; however, early detection of breast cancer metastasis is crucial and challenging to enable surgical removal of the primary tumor and perform a systematic lymphadenectomy to eliminate invasion of the tumor. Herein, we report real-time tracking of the metastasis of orthotopic breast cancer with background-free near-infrared long-persistent luminescence (NIR-PL) imaging, and its guidance for the surgical removal of lymph nodes. The NIR-PL imaging is based on Cr3+/Nd3+ codoped ZnGa2O4 (A-ZGCN) nanoparticles with a superlong afterglow time of more than 15 days. We show that the detection sensitivity of metastasis of cancer cells with the NIR-PL imaging is higher than the classic bioluminescence imaging. We find that the metastasis of breast cancer cells to lymph nodes occurred as early as on the third day after orthotopic inoculation of breast cancer cells and followed an order of the proper axillary lymph node (PALN, day 3) > accessory axillary lymph node (AALN, day 6) > accessory mandibular lymph node (AMLN, day 9) > mandibular lymph node (MLN, day 25). In addition, we show that the NIR-PL nanoprobes (i.e., A-ZGCN NPs) displayed 17% radioenhancement, which was used for radiotherapy of orthotopic breast cancer to further prevent and reduce its metastasis to other organs. The radiotherapy treatment is superior to surgery for removal of the tumor accompanied by a NIR-PL imaging-guided lymphadenectomy. Our work demonstrates the great potential of NIR-PL imaging and the corresponding nanoprobes for tracking metastasis of cancer cells and for radiotherapy.