Nerve-tumor crosstalk in tumor microenvironment: From tumor initiation and progression to clinical implications.

The autonomic nerve system (ANS) innervates organs and tissues throughout the body and maintains functional balance among various systems. Further investigations have shown that excessive activation of ANS not only causes disruption of homeostasis, but also may promote tumor formation. In addition, the dynamic interaction between nerve and tumor cells in the tumor microenvironment also regulate tumor progression. On the one hand, nerves are passively invaded by tumor cells, that is, perineural invasion (PNI). On the other hand, compared with normal tissues, tumor tissues are subject to more abundant innervation, and nerves can influence tumor progression through regulating tumor proliferation, metastasis and drug resistance. A large number of studies have shown that nerve-tumor crosstalk, including PNI and innervation, is closely related to the prognosis of patients, and contributes to the formation of cancer pain, which significantly deteriorates the quality of life for patients. These findings suggest that nerve-tumor crosstalk represents a potential target for anti-tumor therapies and the management of cancer pain in the future. In this review, we systematically describe the mechanism by which nerve-tumor crosstalk regulates tumorigenesis and progression.

Serum microRNA-195 is down-regulated in breast cancer: a potential marker for the diagnosis of breast cancer.

MicroRNA-195 (miR-195) is a tumor suppressor that plays an important role in tumorigenesis. There are few studies on miR-195 expression in breast cancer patients and the results have been inconsistent; therefore, this study examined miR-195 expression in the serum of BC patients. Samples from 102 normal subjects and 210 subjects with BC who had detailed clinical follow-up information available were selected. An internal reference (miR-16) and serum miR-195 were amplified and quantitatively detected by SYBR green-based real-time RT-PCR. We analyzed the differences in miR-195 levels between BC and healthy cases and the relationships between the miR-195 level and TNM stage and other clinicopathological parameters. In addition, changes in miR-195 levels were examined for 21 BC cases using paired samples before and after neoadjuvant chemotherapy. miR-195 was downregulated in BC compared with control samples (P = 0.000, Mann-Whitney U test). The sensitivity and specificity of miR-195 in the diagnosis of BC were 69.0 and 89.2 %, respectively; whereas, the sensitivities of carcinoembryonic antigen (CEA) and carbohydrate antigen 153 (CA153) were only 15.08 and 21.1 %, respectively. Remarkably, serum miR-195 had higher sensitivity, 73.97 % (108/146), as a tumor marker in the diagnosis of early stage BC [ductal carcinoma in situ, tumor-node-metastasis (TNM) I, II] compared with the conventional tumor markers CA153 and CEA (12.41 and 7.59 %). Moreover, compared with CEA and CA153, miR-195 had a higher sensitivity for detecting the response to neoadjuvant chemotherapy and significantly increased, more than twofold, after neoadjuvant chemotherapy (P = 0.025, paired t test) in 52.381 % (11/21) of BC cases. However, there were no significant relationships between miR-195 expression and other clinicopathological parameters (TNM stage/pathotype/ER/PR/lymph node status). Our data indicate serum miR-195 is a promising tumor marker for BC diagnosis and general screening, especially for early stage BC. The high sensitivity of miR-195 to neoadjuvant chemotherapy may lay the foundation for future studies on the use of miRNA-based methods for monitoring BC treatment and therapy.