Research finds links between mutations in the genes KRAS, STK11, and TP53 and differences in lung cancers

Summary

This research looked at mutations (changes) in specific genes and how they relate to each other in a tumor. They looked for links between the mutations and differences in lung cancer growth, survival, and the body’s ability to fight cancer. The researchers looked for mutations in these genes:

  • KRAS – a gene that starts cell growth. Mutations in this gene are common in lung cancers.
  • STK11 and TP53 – genes that help stop cells from growing out of control. Mutations in either gene raise cancer risk.

What were the main results?

The researchers found that:

  • Tumors with changes in TP53 grew more quickly
  • Tumors with changes in STK11 also had more active changed KRAS genes and a weaker response from the body to stop cancer cells

The researchers suggest that lung cancer patients whose tumors have mutations in STK11 may need more treatments or stronger treatments. With more research, this could help inform treatment decisions for patients with these gene mutations.

  • Illustration of a magnifying glass representing researchers looking closely at their study.

    What did researchers study?

    The researchers studied different gene mutations found in lung cancer tumors. They also studied how these gene mutations affected the features of the tumors.

  • Illustration of two people. One has their arm raised representing volunteering.

    How many patients' data did researchers study?

    Researchers studied the tumors and medical records of 442 patients with lung cancer who joined Total Cancer Care® (TCC).

    Researchers also studied genetic data from 483 lung cancer tumors from The Cancer Genome Atlas (TCGA).

  • Illustration of a bar graph with a magnifying glass representing types of research.

    What kind of research was this?

    This was an observational study. Researchers looked at (observed) cancer data to learn more about how cancer works.

The results of this research alone should not be used to make health decisions. It takes many studies for researchers to confirm findings and use them in patient care.

Why was this research needed?

Researchers wanted to learn more about gene mutations that happen in lung cancer to look for better treatments. Lung cancer is the leading cause of cancer deaths worldwide. Previous research found that mutations in the gene KRAS happen often in lung adenocarcinoma, which is the most common type of non-small cell lung cancer (NSCLC). It usually grows in the outer parts of the lung. The KRAS gene plays a role in cell growth and mutated genes can cause cancer cells to grow and spread in the body. However, there are currently no cancer treatments that target KRAS gene mutations.

Previous research has found that mutations in 2 other genes, called STK11 and TP53, are also common in lung cancer and happen with KRAS mutations. Both STK11 and TP53 are genes that help stop cell growth and mutations in these genes allow cancer cells to grow out
of control.

Some cancer treatments, such as immunotherapy, use the body’s own immune system to help detect and fight cancer. The immune system is the organs and cells that protect the body from infection and illness.

In this study, researchers wanted to learn more about the different features of lung cancer tumors with KRAS gene mutations by looking at links between mutations in the genes KRAS, STK11, and TP53 and:

  • Tumor growth
  • The immune system’s response (ability to target cancer cells)
  • Overall survival (how long people lived)

  • How many patient's data did researchers study?

    First, researchers studied tumor samples and medical records of 442 patients with lung adenocarcinoma who joined TCC between 2006 and 2010. Of the 442 patients, 335 (91%) reported they were ever smokers and:

    • 154 (35%) had KRAS gene changes
    • 68 (15%) had STK11 gene changes
    • 111 (25%) had TP53 gene changes

    Then, researchers studied genetic data from 483 lung cancer tumors from The Cancer Genome Atlas (TCGA) to confirm their findings.

  • What kind of research was this?

    This was an observational study. Researchers looked at (observed) cancer data to learn more about how cancer works.

    This kind of study can further cancer research aimed at developing new treatments, tailoring treatments to patients, and identifying a patient’s cancer sooner.

  • What happened during this research?

    The researchers looked at genetic data from tumor samples and medical records to learn:

    How often STK11 and TP53 mutations happen in tumors that also have KRAS mutations
    For each tumor sample, they looked for mutations in the genes KRAS, STK11, and TP53. They looked at if a tumor had mutations in one or more of these genes and for differences in survival.

    If mutations in the genes STK11 and TP53 affect tumors with KRAS mutations
    The researchers measured patterns of activity in tumors with KRAS mutations. They measured if this activity changed when a tumor also had STK11 and TP53 mutations.

    To confirm their results, the researchers looked at data from 483 lung cancer patients from the TCGA dataset.

    If mutations in the genes KRAS, STK11, and TP53 affect cancer growth and the immune system’s response
    The researchers looked for other patterns of activity in tumors related to mutations in one or more of the 3 genes to see if they affect:

    • How quickly tumors grow
    • How the immune system responds (such as targeting tumor cells)

  • How researchers designed this study

    Researchers started with 442 patients’ tumors and medical records from TCC.

    Researchers looked at each tumor for changes in KRAS, STK11, and TP53.

    • 154 tumors had KRAS changes
    • 111 tumors had TP53 changes
    • 69 tumors had STK11 changes

    See infographic

  • What were the main results?

    Researchers found that:

    • Tumors with mutations in STK11 also had more active mutated KRAS genes and a weaker response from the body to stop cancer cells
    • Tumors with mutations in TP53 grew more quickly

    Researchers concluded these findings show that tumors with mutations in STK11 or TP53 may grow in different ways:

    • Tumors with STK11 mutated genes may weaken the immune system’s response and require stronger immunotherapy treatment
    • Tumors with TP53 mutated genes may grow and spread more quickly

    Other results

    The researchers also learned:

    Few tumors had mutations in all 3 genes

    Of the 442 tumors, only 4 tumors (less than 1%) had mutations in all 3 genes: KRAS, STK11, and TP53. 190 (43%) did not have mutations in any of the 3 genes.

    It was also less common for tumors to have mutations in both STK11 and TP53 without any KRAS mutations. Specifically, only 7 tumors (about 2%) had mutations in both STK11 and TP53 but not KRAS.

    Tumors with mutations in KRAS had worse survival 

    When they looked at differences in the gene mutations and survival, researchers found that tumors with:

    • KRAS mutations had worse survival compared to those without KRAS mutations
    • STK11 or TP53 mutations were not related to survival

  • How has this research helped?

    This helped researchers better understand the mutations in the genes KRAS, STK11, and TP53 that happen in lung cancer. In particular, this research identified that mutations in the genes affect the ways that cancer grows. They believe this could help tailor cancer treatment based on gene mutations, such as those in STK11 and KRAS.

    The researchers point out that more studies are needed to further understand the pathways through which STK11 gene mutations strengthen KRAS mutations and weaken the immune system’s response.