Transcriptomics Plus ‘Immune Tolerance’ of Normal Tissue Shows Promise in Lung Cancer Prognosis

Posted: Tuesday, September 27, 2022

September 21, 2022
Precision Oncology News - Caroline Hopkins

NEW YORK – Researchers involved in the Worldwide Innovative Networking
(WIN) Consortium have shown, for the first time, that biomarkers detected in
normal lung tissue can be valuable for predicting lung cancer patients'
likelihood of post-surgery recurrence.

With several exceptions — namely germline testing — most biomarker insights in oncology rely on analysis of tissue or cells from the cancerous tumor itself. This is especially true in lung cancer, where somatic mutations or expression of genes in tumor tissue are routinely used to guide treatment decisions. Even most blood-based biomarker tests are tumor-centric, focusing on pieces of DNA shed from the tumor tissue circulating in blood.

Now, for the first time, researchers have demonstrated that the normal, healthy tissue in a patient's lung — that is, non-tumor lung tissue — can be rich in biomarkers that shed light on a patient's likelihood of relapse after surgery, information that oncologists can use to guide adjuvant therapy choices.

In a paper published last week in JCO Precision Oncology, WIN researchers, including Vladimir Lazar, the consortium's founder and chief scientific and operating officer, demonstrated that the so-called “immune tolerance profile” of normal lung tissue, when paired with a tumor-normal transcriptomics-based score, may allow oncologists better insights into patients' prognoses and the treatments most likely to benefit them.

“The problem is that today, there is no biomarker for predicting recurrence,” Lazar said. “The recurrence risk, today, is guided by stage and histology.”

In the retrospective analysis described in the JCO Precision Oncology paper, Lazar and colleagues analyzed data from the observational CHEMORES study, which followed 123 early-stage non-small cell lung cancer patients who
underwent surgical resection. Following surgery, based on their treating oncologists' decisions, 61 of these patients received adjuvant chemotherapy, while the other 62 did not. The observational study followed these patients for 92 months.

Researchers in the CHEMORES study performed DNA sequencing and gene expression analysis of resected tumor and normal lung tissue samples obtained during the patients' surgeries. These data were available to WIN researchers who aimed to test their hypothesis in silico that the differential gene expression between the tumor and normal lung tissues, together with the immune competent versus immune tolerant status of the normal lung tissue, could explain patients' risk of recurrence.

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