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Shu-jun Cheng On Finding Lung Cancer Biomarkers Using In Vitro Method

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At A Glance

Name: Shu-jun Cheng

Position: Director, Chinese Nationwide Basic Research, Cancer Institute Hospital, Beijing.

Professor of genetic toxicology at Chinese Academy of Medical Sciences and Peking Union Medical College.

Background: First years of medical study, Beijing University Medical Center, 1962.

MD, Peking Union Medical College, 1965.

Visiting scientist, Medical College Of Ohio at Toledo, 1986.

International work in Paris, Netherlands and over 10 other countries, mostly in Europe.

Tell me about your work in finding biomarkers for lung cancer.

The lung cancer mortality rate is ranked first worldwide and also in China. It’s a big challenge for us. And the survival rate is very poor. So the most important question is the early diagnosis. If we can not get early diagnosis then it will be very difficult to improve the five-year survival rate for lung cancer. So early diagnosis is a big challenge for us. At the present time, we can rely on the imaging diagnosis — that’s the most important — and also rely on the pathology. But at the present time, even relying on imaging systems, it is still very difficult for us to find the very early stage of lung cancer. So we have to find another way to detect early stage of lung cancer, and any kind of cancer. So during the past several years, people started focusing their interest on the identification of so-called tumor-related biomarkers in human blood. But blood is so complicated. There are lots of protein with low abundance. At the present time there is no way to find the low-abundance protein. Many of them might be useful for the early detection of lung cancer. So during the last three years in our lab, we have been trying to find is there any way we can detect the low-abundance biomarkers in human blood? We developed a way in which first we used the human lung tissue — first make primary culture in vitro, and in vitro all the medium are chemically defined. We know every component in medium. So when the tumor tissue grows in vitro, it should continue to release proteins as it did in vivo. But it is not the same. But it’s not entirely different. There may be some similarity when the tumor secretes something in vivo and when it’s cultured in vitro. In vitro, the environment is very safe. The medium is defined — we know everything. So when the tumor cell releases something into the medium then for us it is very easy for us to catch it. So using this way, we have identified more than 200 proteins, most of them new proteins.

What is the next step now that you have identified these proteins in vitro?

Now the question for us to answer is if this protein is identified in vitro, can you detect the same protein in vivo? Otherwise, it’s just an artifact. So the next step. We should detect this protein identified in vitro in human blood. And the answer is yes. We can detect the protein identified in vivo. So for the first time, we really detect more than 14 proteins in lung cancer patient blood. Among them, 11 are already identified. And the seven of the 11 proteins were not reported before. That’s the first time the seven proteins were identified in human blood. And some of the proteins in lung cancer are overexpressed and down-expressed. So next, we should do a so-called protein profile because not any single biomarker can be useful precisely for guideline tumor diagnosis, treatment and prognosis. We should use profiling. That means we profile different proteins overexpressed or down-expressed. When we get the profile, then we can make protein chips. When we get chips, then we can detect the protein alteration in blood in a high-throughput way. In this way we can find the profiling of tumor markers in blood. In this way we can approach step by step to the early diagnosis or individualized treatment for not only lung cancer but for any kind of other cancer. So this is our idea.

How specific are these proteins for lung cancer?

At the present time we can not say that each of these proteins identified in our case is specific for lung cancer. We need to do more studies to find if these protein alterations can be found in colon cancer or stomach cancer. We should do more. But anyway, we find the difference in protein alteration between lung cancer patient blood and non-malignant lung cancer patient and healthy people. That’s the first step. So the next step is we’ll do more for other types of cancer. But this model will be very useful. Because the in vitro model can give us a simple way to give us some new information — what kind of protein could be released or secreted by cancer cells? And then, with this information, we can detect the protein in vivo. At the present time, because we have no idea what kind of protein can be released by cancer cells, this kind of way can provide us tremendous information.

At the present time are there biomarkers being used for the early detection of lung cancer?

At the present time, no — there are not any specific lung cancer biomarkers available. Not yet.

Are you planning on trying to get this approved for clinical trials?

Yes. But we should do further studies.

Going back into your background, were you always involved in proteomics and cancer research?

Yes. I’m a medical doctor, so I spent all my life for cancer research. Originally I focused on carcinogenesis at the DNA level and RNA level. In the recent years, I focused my effort on proteomics because proteins are much more related to clinical use for early diagnosis, for the individual treatment, for prognosis. But we should do the research in a systematic approach that focuses from DNA, to RNA, to proteins, to chromosomes —not just relying on one level. We should rely on a systematic approach. Proteomics is the key study for the clinical use. Most studies investigate only at one level. Now people are changing to investigate this kind of complicated disease in a systematic approach at different levels including DNA, RNA, protein and chromosomes.

Before you started with proteins, did you try to find other methods for early lung cancer diagnosis?

Yes. We also used the microarray. So we combined at the DNA level, RNA expression level and proteomics.

Were you successful in finding genes with the microarray approach?

Yes. We already cloned more than 100 genes from our lung cancer related library and we used these genes to prepare our own lung cancer-related microarray. Now the work is underway. At the present, we are preparing 1,600 genes on a chip. We will check 1,600 genes that might be related to lung cancer.

Do you think you might combine that with the proteomics chip?

Yes.

How far away do you think the world is from a diagnostic test for lung cancer?

I think there’s still a long way to go because cancer is so complicated. It’s a complicated genetic disease. And lung cancer has different types, different stage. There is still a long way to go for us to make an early diagnosis to increase the five-year survival rate. But we will certainly approach it step by step. It’s hard for me to answer the question of how many years before a diagnostic test exists, but it’s a good question.

What are the next steps now that you’ve found these biomarkers?

We have a platform but we need to do more. We started with this platform to do lung cancer. Now we need to do stomach cancer, liver cancer to see if this platform can give us more information. At the same time we’ve already set up a huge tissue bank — the cancer tissue bank, including blood. So we should check every protein identified in vivo in our tissue bank, our blood bank. So the final answer should come from the tissue bank.

Right now do you have enough clinical samples to do large-scale studies?

Yes. We will capture our data soon. We will send our data for publication soon.