|Kazufumi Honda||Graduate School Professor|
|Nami Miura||Assistant Professor|
|Reiko Tokita||Technical Staff|
|Keiko Takeuchi||Assistant Support Staff|
Using innovative proteomic, metabolic and genomic techniques, the research interests of our department will focus on clarifying the molecular and cellular mechanisms of cancer promotion and progression. With the aim of discovering targets for early detection, molecular therapy and personalized medicine, we have undertaken comprehensive protein, metabolite and gene expression profiling of various cancer cell lines and cancer tissues, as well as sera/plasma from cancer patients.
<Practical implementation of effective blood biomarker-based pancreatic cancer screening>
The biomarker is an isoform of apolipoprotein (apo) A2, a protein that circulates in the blood, and the NCC Research Institute has been collaborating with the National Cancer Institute (NCI) in the United States to assess biomarker effectiveness for detecting early-stage pancreatic cancer and precancerous conditions associated with a high risk of pancreatic malignancy, and to develop a test kit. Based on the results of this study, trial screenings for pancreatic cancer were carried out in a collaborative study with Kobe University and others starting in 2015. In those trial screenings, abnormal biomarker values enabled detection of pancreatic cancer and precancerous conditions associated with a risk of pancreatic malignancy. A follow-up study using community-wide health examinations in Kagoshima Prefecture, Japan, began in July 2017.
<Practical application of predictive biomarker for adjuvant chemotherapy>
In the reanalysis of the National Cancer Institute Canadian Clinical Trial Group JBR.10, which led to the adoption of adjuvant cisplatin-based chemotherapy for patients with resected stages-IB to IIIA non-small cell lung cancer (NSCLC), we demonstrated a significant clinical benefit of adjuvant chemotherapy for overall survival only in the actinin-4 (ACTN4) high expression group. The data suggested that ACTN4 is a potential predictive biomarker for efficacy of adjuvant chemotherapy in early-stage patients with NSCLC. We are currently preparing a test kit for confirming ACTN4 gene amplification and protein expression with surgical specimens. In the future, we are aiming to develop a diagnostic regent kit in order to improve personalized medicine in adjuvant chemotherapy.
<Molecular mechanisms of cancer invasion and metastasis>
Metastasis is one of the major obstacles in the treatment of any cancer. Surgical management of cancer with no lymph node or organ metastasis is generally uncomplicated, but the treatment of metastatic disease remains challenging. We focus on molecules involved in invasive and metastasis and analyze these molecular mechanisms. In addition, circulating tumor cells (CTC) are thought to have the metastatic ability to multiple organs; therefore, it is important to study CTC in order to understand metastasis.
1) Analysis of molecular mechanisms of actinin-4
Acquisition of increased motility by cancer cells seems to be a requirement for cancer invasion and metastasis, and during the process of cell movement, the actin cytoskeleton is dynamically remodeled by the functions of various classes of actin-binding proteins. In our department, Honda et al. isolated ACTN4 as an actin-binding protein involved in the bundling of actin fibers and promotion of cell motility. We are analyzing the medical and biological significance of ACTN 4 for cancer.
In pancreatic cancer, ovarian cancer, colon cancer, esophageal cancer, and head and neck cancer, the overall survival time of the ACTN4 high expression patient group was significantly shorter than that of the low expression patient group. In stage I lung adenocarcinoma, the patient group with ACTN4 gene amplification had a significantly higher risk of death when compared to the patient group without gene amplification. In addition, an ACTN4 splice variant that is expressed specifically in lung high-grade neuroendocrine tumor (LCNEC) was useful for diagnosis of LCNEC, and we found that the ACTN4 splice variant is a biomarker for predicting prognosis. Furthermore, we clarified that overexpression and knockdown of ACTN4 in cell lines is correlated with cell motility.
2) Analysis of the molecular mechanism of CTC
CTC are tumor cells that have passed into the blood from cancer tissue and are thought to have metastatic potential. There are thought to be few CTC in the blood, and it is difficult to analyze the molecular mechanisms of these cells. Therefore, we aim to analyze the functions of CTC using various omics analytical methods.