Researchers identified a biomarker that detects the most common type of lung cancer in its earliest stage. The discovery could one day change how long lung cancer patients live. These findings were published in the American Journal of Respiratory and Critical Medicine (doi:10.1164/rccm.201412-2226OC).
According to the National Cancer Institute, lung cancer kills an estimated 158 000 Americans each year, which is as many as the next 4 most deadly cancers combined. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers.
“When NSCLC is detected early, patients have a 70% chance of being alive 5 years later. When NSCLC is detected at an advanced stage, 5-year survival drops to less than 10%,” said senior investigator Pei-Jung Lu, PhD, professor of medicine at National Cheng-Kung University in Taiwan.
Lu and his colleagues tested Huntingtin-interacting protein 1 (HIP1) as a potential new biomarker, also investigating its role in lung cancer progression and metastasis, the cause of most lung cancer deaths. In addition to serving as a biomarker, the researchers found, HIP1 represses the mobility of lung cancer cells in laboratory studies and suppresses metastasis in a mouse model.
The study is the first to describe HIP1 involvement in the progression of adenocarcinoma, the most common type of NSCLC.
The researchers began by examining lung tissue from 121 patients. They found that HIP1 was more highly expressed in patients at the earliest stages of disease than in those at later disease stages. The researchers also studied the correlation between HIP1 expression in early stages of the disease (stage I-II), and found a significant correlation between those patients who expressed higher levels of HIP1 and longer survival, indicating HIP1 is a prognostic biomarker.
They also studied the correlation between HIP1 and cellular mobility in vitro and in a mouse model of adenocarcinoma. In the laboratory, HIP1 expression was inversely associated with cancer cell mobility. The researchers confirmed those results in their mouse model. High levels of HIP1 expression were significantly associated with fewer metastatic tumor cells.
The researchers then investigated the mechanisms behind the ability of HIP1 to suppress cellular mobility and metastasis. They found that HIP1 modulates Akt, a protein kinase that regulates the epithelial-mesenchymal transition, which in turn facilitates cell invasion and the beginning of metastasis.
“If we can restore HIP1 levels and functions, we may be able to stop or prevent human lung cancer metastasis in the early stage,” Lu said. “To bring this discovery to clinical care, we now need to identify the regulatory factors of the HIP1 gene that are targetable through gene therapy or small molecule interventions.”