Potential Molecular Mechanisms That Increase COVID-19 Risk in Lung Cancer Highlighted

This experimental research suggests the expression levels of certain genes might help explain why people with lung cancer often have more severe cases of COVID-19.

A new analysis offers insights into the molecular mechanisms that may put people with lung cancer at an increased risk of severe disease when they are infected with SARS-CoV-2, according to a new report in Gene.

A team of Brazilian investigators wrote that genes associated with SARS-CoV-2 entry have variable expression in patients with lung cancer. They also identified 22 lung genes that are differentially expressed in both lung cancer and COVID-19, among other findings. They explained that people with cancer tend to have higher rates of severe cases of COVID-19, but it is not yet clear exactly which mechanisms lead to the associations.

“The highest frequency of severe events occurs in COVID-19 patients with hematologic and lung cancers and/or metastasis,” they wrote.

One possible reason for the link with lung cancer, they said, is the increased expression of angiotensin-converting enzyme 2 in people with lung cancer. Viral spike proteins of SARS-CoV-2 bind to ACE2, which is more highly expressed in lung adenocarcinoma and squamous cell carcinoma compared with normal tissues, the authors noted.

They decided to analyze how the molecular interactions between SARS-CoV-2 and lung cancer cells and tissues might shed light on the mechanisms by which people with lung cancer are at a greater risk of severe COVID-19. The used transcriptome data of small-cell lung cancer (SCLC) or non–small cell lung cancer (NSCLC) tumors, as well as normal and cancerous lung cells infected with SARS-CoV-2.

“We aimed to characterize molecular mechanisms potentially associated with COVID-19 development and severity in lung cancer patients and to predict the SARS-CoV-2-host cell interactome,” they wrote.

The analysis led to several key findings. First, they found that the gene expression profiles of SARS-CoV-2–infected lung cell lines were more like the profiles of primary lung tumors compared with nonmalignant lung tissues. They also found that people with SCLC and NSCLC had increased expression levels of BRCA1 and CENPF, both cancer genes known to interact with SARS-CoV-2.

“We also found that TRIB3, a gene coding a putative host-SARS-CoV-2 interacting protein associated with COVID-19 infection, is co-expressed with the upregulated genes MTHFD2, ADM2, and GPT2 in all tested conditions,” the authors said.

Finally, they noted that they identified biological processes and 22 host mediators of SARS-CoV-2 infection and replication that may be tied with COVID-19 development and severity.

Although the investigators said their findings offer indications of why COVID-19 can be particularly dangerous in people with lung cancer, they also noted the limits of their research. The analysis relied on publicly available transcriptome data and computational predictions, which they said may differ from real-world patients who have lung cancer and COVID-19. The analysis also did not delve into different variants of SARS-CoV-2, and they said cell lines—which were the basis of this investigation—do not capture all aspects of bulk tumor tissues.

“Nonetheless, considering the urgent need to better understand COVID-19, especially in high-risk patients, such as lung cancer patients, this study opens new exploratory opportunities to address the genetic background associated with SARS-CoV-2 infection,” they said.


Cury SS, Oliveira JS, Biagi-Júnior CAO, et al. Transcriptional profiles and common genes link lung cancer with the development and severity of COVID-19. Gene. 2023;852:147047. doi:10.1016/j.gene.2022.147047

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