Could RNAs assist in treatment decisions for stage II colon cancer patients?

RNAs may help identify stage II colon cancer patients who could benefit from chemotherapy following surgery. In a newly published study, investigators assess the biomarker potential of RNAs to identify such patients.

The decision to treat patients with stage II colon cancer with adjuvant chemotherapy remains controversial. Therefore, there is an urgent need to identify reliable prognostic biomarkers that may be used to identify which patients would benefit from chemotherapy following surgery. In a ground-breaking new study in The American Journal of Pathology, investigators assess the biomarker potential of RNAs in stage II colon cancer.

Lead investigator Lasse Sommer Kristensen PhD, Department of Biomedicine, Aarhus University, explains: “There are currently no reliable biomarkers for determining whether stage II colon cancer patients would benefit from adjuvant chemotherapy following surgery. Identification of new risk-stratification biomarkers is beneficial - it may spare many patients who are actually cured by the surgery from toxic side effects of chemotherapy while still selecting patients who would benefit from it.”

Using total RNA-sequencing, investigators profiled the landscape and differential expression of coding RNA, linear noncoding RNA, and circular RNA in stage II colon cancer patients with and without recurrence of the disease, as well as in stage III colon cancer patients. They also profiled adjacent normal tissues and liver metastases. The biomarker potential of differentially expressed RNAs in stage II colon cancer was subsequently evaluated. Patient data collected included age, sex, date of surgery, chemotherapy treatment, tumour location, and date of recurrence. Histopathologic data were collected through the Danish Pathology Registry (Patobank) and included staging status, histologic subtype, tumour differentiation, mismatch repair status, and mutational analysis, if performed.

Sixty-two samples from 52 patients were included in the analysis: 18 patients with stage II colon cancer without recurrence, 10 patients with stage II colon cancer with recurrence, eight patients with stage III colon cancer with recurrence, 16 liver metastases, six adjacent normal colon tissues, and four adjacent normal liver tissues.

The investigators found that RNAs with housekeeping functions, such as small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), and small Cajal body-specific RNAs (scaRNAs), were globally up-regulated in stage II patients who experienced recurrence compared to those who did not. Housekeeping RNAs are constitutively expressed and mostly involved in RNA splicing regulation and rRNA modification.

This is the first study to comprehensively describe the landscape of mRNAs, linear noncoding RNAs, and circular RNAs in local and locally advanced colon cancer and unveiled numerous differentially expressed RNAs across various classes between recurrent and nonrecurrent colon cancer. The expression of these RNA classes is retained in liver metastases, suggesting that they may play important roles in the metastatic process.

Dr Kristensen notes: “We were the first to profile many different types of RNA in stage II colon cancer patients with different outcomes and discovered novel individual biomarkers as well as entire classes of RNA that are commonly deregulated in patients with poor outcomes. Furthermore, many of these classes of RNAs showed great prognostic potential to assist treatment decisions in stage II colon cancer that should be validated in larger groups of patients.”

  • Korsgaard U, García-Rodríguez JL, Jakobsen T, et al. The Transcriptional Landscape of Coding and Noncoding RNAs in Recurrent and Nonrecurrent Colon Cancer. Am J Pathol. 2024 May 3:S0002-9440(24)00163-9.

           doi: 10.1016/j.ajpath.2024.04.003. 


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