Biomarker of Early-Stage Lung Cancer Identified

A biomarker that detects the most common lung cancer in its earliest stage has been identified and this discovery could one day change how long lung cancer patients live.

Non-small-cell lung cancer (NSCLC) carries a poor survival rate mainly due to metastasis; however, the molecular mechanisms that govern NSCLC metastasis are undescribed, though NSCLC accounts for about 85% of all lung cancers.

Scientists at the National Cheng-Kung University (Tainan, Taiwan) by examined lung tissue from 121 patients. They investigated role of Huntingtin interaction protein-1 (HIP1) in lung cancer progression and metastasis, the cause of most lung cancer deaths. In addition to serving as a biomarker, the team found, HIP1 represses the mobility of lung cancer cells in laboratory studies and suppresses metastasis in a mouse model of the cancer.

The investigators found that those in the earliest stages of the diseases expressed more HIP1 than those in the later stages of the disease. They 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 that HIP1 was 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, they found that HIP1 expression was inversely associated with cancer cell mobility. They confirmed those results in their mouse model. High levels of HIP1 expression were significantly associated with fewer metastatic tumor cells. Then they investigated the mechanisms behind HIP1's ability to suppress cellular mobility and metastasis. They found that HIP1 modulates the serine/threonine-specific protein kinase B (Akt) that regulates the epithelial-mesenchymal transition, which in turn facilitates cell invasion and the beginning of metastasis.

Pei-Jung Lu, PhD, a professor of medicine and senior investigator of the study, said, “If we can restore HIP1 levels and functions, we may be able to stop or prevent human lung cancer metastasis in the early stage. 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.” The study was published on November 23, 2015, in the American Journal of Respiratory and Critical Medicine.

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