New Biomarker Candidates for Colon Cancer
New biomarker candidates may help determine which colon cancer patients are most likely to benefit from chemotherapy
Michael Schubert, PhD, is a veteran science and medicine communicator. He holds graduate degrees in biochemistry and molecular biology with a research focus on chromatin structure and function and has written on subjects from subspeciality pathology to fictional science. In addition to writing and editing, he is co-director of the Digital Communications Fellowship in Pathology and Course Trainer at the Lightyear Foundation, an initiative aimed at making science accessible to all.
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Deciding whether or not colon cancer patients will benefit from chemotherapy after surgery can be a challenge. Typically, patients with stage I cancers are not offered adjuvant therapy, whereas those with stage III cancers are. Stage II colon cancer—in which the tumor has penetrated the intestinal wall, but not metastasized—is more controversial, with some experts favoring treatment to avoid recurrence and others preferring to spare patients the side effects of unnecessary chemotherapy.
To gain more insight into which patients might benefit from further treatment after surgery, a team of researchers in Denmark used total RNA sequencing to profile the transcriptomic landscape of stage II and III colon adenocarcinoma. Tissue from the primary or metastatic tumors of 52 colon cancer patients were profiled in a new study in The American Journal of Pathology, which revealed a number of transcripts with no preexisting link to colon cancer.
Many housekeeping RNAs—particularly small nucleolar RNAs (snoRNAs), small nuclear RNA (snRNA) pseudogenes, and ribosomal RNA (rRNA) pseudogenes—were globally upregulated in patients with stage II or III colon cancer who experienced a recurrence relative to those who did not. Described for the first time in the study, the relationship between high levels of housekeeping RNAs and disease progression could not only potentially serve as a biomarker for treatment decision-making, but it could also guide research into factors that drive recurrence and metastasis in colon cancer.
The study authors also identified 117 individual RNA transcripts with strong prognostic potential for recurrence (area under the curve >0.9 during receiver operating characteristics analysis); these included snRNA and rRNA pseudogenes, snoRNAs, mRNAs, long noncoding RNAs, and vault RNAs. Of the 10 most promising biomarker candidates, most were upregulated in people whose cancers recurred, but the novel protein-encoding mRNA (ENSG00000288570) and a transcribed unitary pseudogene (C22orf46) were less abundant in recurrent cancers than in stage II tumors without recurrence.
The authors recommend further investigation of these “top 10” candidates as potential biomarkers for identifying stage II colon cancer patients who would benefit from adjuvant therapy to prevent recurrence, but also recommend mechanistic studies to elucidate the role these RNAs play in disease relapse and metastasis.