Non-small cell cancer (NSCLC) tumor markers are signs of specific types of tumors. Doctors look for these markers to help aid their diagnosis and treatment of lung cancer.

Doctors use several tests to measure cancer and tumor markers, both during diagnosis and throughout treatment. Regular testing can help measure the presence and stage of cancer in certain areas and gauge a person’s response to treatment.

This article looks at tumor markers, how they relate to NSCLC, types of NSCLC tumor markers, tests and normal ranges for tumor markers, and whether they are a reliable diagnostic tool.

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A tumor marker is a specific compound related to a given tumor cell doctors are testing for.

Tumor markers tend to be proteins or other compounds that cancer cells excrete or create faster than healthy cells. They have to be different from healthy cells in order for doctors to get an accurate reading.


In NSCLC, testing for these tumor markers may help doctors identify the sites, stage, and possible response to treatment of a person’s cancer. They may also help identify specific mutations from the tumor itself, which may help with treatment.

To get a better overall picture, a doctor may take many different samples to check tumor marker concentrations in a person’s blood, urine, or stool.

Knowing specific details about tumor markers for a given cancer can be very helpful. This information may help doctors screen for cancer before other tests, and differentiate NSCLC from other conditions that cause similar symptoms.

For known cancer cases, measuring tumor markers may help determine the disease course, such as estimating how aggressive the cancer will be. Doctors may also test for tumor markers in different tissues to check if it has spread.

This information may help determine what treatments could be effective against the specific type of cancer. Regular monitoring of tumor markers may also help identify the response to cancer treatment.

Non-small cell lung cancer is the most common form of lung cancer, accounting for about 85% of all lung cancer cases.

Diagnosis and differentiation

Several types of cancerous cells may occur with NSCLC, including the three main types:

Depending on the type of cancerous cell and cancer itself, doctors may look for a number of different tumor markers.

They may use markers such as thyroid transcription factor 1, napsin A, p40, p63, and cytokeratin 5/6 to help differentiate between adenocarcinoma and squamous cell carcinoma.

A few tumor markers that may be a reference point for a diagnosis of NSCLC include:

  • carcinoembryonic antigen (CEA)
  • cytokeratin 19 fragment antigen (CYFRA21-1)
  • squamous cell carcinoma antigen (SCC Ag)
  • prolactin (PRL)

Some other markers may also increase in cases of NSCLC, including different carbohydrate antigens (CA):

  • CA125
  • CA15-3
  • CA19-9
  • CA72-4

These are not diagnostic tools, but an increase in these carbohydrate antigens along with other tumor markers may be a sign of NSCLC.

Tumor markers that may help differentiate NSCLC from small cell lung cancer include circulating progesterone-releasing peptide (ProGRP) and neuron-specific enolase (NSE).

Some tumor markers will come from testing the tumor itself, including:

Treatment progression

Doctors will also use tumor markers, such as CYFRA21-1, to check on the progress of treatment or recurrence of cancer.

Doctors use a few different methods to test for tumor markers, including:

A doctor will take a sample of the appropriate fluid or tissue and send it to a lab for testing.

The type of test will vary from person to person, depending on factors such as the type of tumor, the stage a doctor suspects a person’s cancer is at, and how far it may have spread.

The ranges of different tumor markers may help doctors diagnose NSCLC or differentiate between NSCLC and other types of cancer or noncancerous lung diseases.

Research from 2017 notes the following cutoff values for “normal” levels of tumor markers:

  • CEA: A level above 5 nanograms (ng) per milliliters (ml) may indicate lung cancer in general and may help doctors differentiate between different types of NSCLC.
  • CA125: A level over 35 units per ml may indicate the presence of specific types of NSCLC when found in combination with other factors.
  • SCC: A level over 2 ng/ml may indicate squamous carcinoma.
  • ProGRP: A level over 50 picograms (pg) per ml is possible in some types of NSCLC, such as large cell carcinoma, but is more common in SCLC. Doctors may consider a range of ProGRP under 100 pg/ml, in combination with other factors, as a way to differentiate between NSCLC and SCLC.

None of these individual factors are enough to make a diagnosis. Doctors will consider many factors during both diagnosis and treatment.

Doctors use tumor markers as a sort of guide throughout diagnosis and treatment. They can provide useful information about cancer’s presence in tissues, its stage, and the effectiveness of treatment.

Tissue biopsies of the tumor itself help doctors identify the type of tumor by its mutations. Knowing what mutations caused the tumor may help doctors recommend targeted therapy for lung cancer if possible.

As a diagnostic tool

Tumor markers may be helpful diagnostic tools for lung cancer.

Research from 2017 found that CYFRA21-1 was the most sensitive single marker for NSCLC, which may help in the diagnosis of the disease.

Additionally, research from 2018 found that a panel that includes testing for PRL, CEA, and CYFRA21-1 was relatively sensitive and specific for diagnosing NSCLC compared to testing for individual tumor markers.

Differentiating between cancer types and subtypes

Tumor markers may also help differentiate between types of lung cancer. Research from 2017 notes that markers such as NSE and ProGRP are reliable tumor markers for SCLC. This can help differentiate between the two types.

They may also help differentiate between types of NSCLC. Specific markers, for instance, may be higher in different types of NSCLC, including:

  • higher levels of CEA and CA125 in adenocarcinoma
  • higher levels of SCC in squamous tumor
  • higher levels of CA125 in large cell lung cancer

Disease course

Tumor markers may also provide some idea of disease course. Research from 2020 found that high levels of CYFRA21-1 in people with advanced NSCLC indicated a poor disease course and survival rate.

Potential issues

With this said, tumor markers are not a certainty. There are some possible issues with using tumor markers.

For example, people can have cancer without having notable changes in tumor markers, and some conditions have few reliable tumor markers to check for.

Additionally, some other health conditions can cause similar increases in the levels of some tumor markers. Depending on the markers doctors are looking for, this may create a false positive for cancer.

Because of these possible limitations, doctors will not rely on tumor markers alone to gather the information they need about a possible cancer case. They will use other tests in addition to tumor marker results to get more comprehensive results to help guide their diagnosis and treatment.

Testing for tumor markers provides doctors with helpful information they can use in cases of non-small cell lung cancer.

Doctors may use the results of tumor marker tests along with results from other tests to guide diagnosis and treatment. More research into the reliability of tumor markers may improve the understanding of how these markers can help guide a diagnosis.