Why not use LINC0219 as a predictor of colon cancer recurrence when some guidelines suggest it plays a role?

LINC0219 Is Not Recommended for Predicting Colon Cancer Recurrence

Current clinical guidelines do not support the use of LINC0219 as a biomarker for predicting colon cancer recurrence, as there is insufficient evidence from high-quality studies to recommend its routine clinical application.

Current Guideline Recommendations for Colon Cancer Biomarkers

The American Society of Clinical Oncology (ASCO) and other major oncology organizations have established clear guidelines regarding which biomarkers should be used in colorectal cancer management:

Recommended Biomarkers:

1. Carcinoembryonic Antigen (CEA)

   • CEA is the only serum marker consistently recommended for monitoring colorectal cancer 1
   • Should be measured preoperatively for staging and surgical planning 1
   • Recommended for postoperative surveillance every 3 months in patients with stage II or III disease for at least 3 years 2
   • Two consecutive rising values above baseline suggest disease progression 2

2. RAS Mutational Testing

   • Mandatory for patients being considered for anti-EGFR therapy 1
   • Should include KRAS and NRAS codons 12,13 of exon 2; 59,61 of exon 3; and 117 and 146 of exon 4 1

3. BRAF p.V600 Mutational Analysis

   • Recommended for prognostic stratification 1
   • Should be performed in deficient MMR tumors with loss of MLH1 to evaluate Lynch Syndrome risk 1

4. Mismatch Repair (MMR) Status Testing

   • Recommended for identifying patients at high risk for Lynch syndrome and/or prognostic stratification 1

Biomarkers NOT Recommended:

The guidelines explicitly state that numerous biomarkers lack sufficient evidence for routine clinical use, including:

• DNA ploidy or flow cytometric proliferation analysis 1, 2
• p53 expression or mutation 1, 2
• ras oncogene (outside of anti-EGFR therapy selection) 1, 2
• Lipid-associated sialic acid (LASA) 1, 2
• Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) 1, 2
• PIK3CA mutational analysis (outside clinical trials) 1
• PTEN analysis 1

Emerging Biomarkers and LINC0219

While LINC0219 has been identified in research as a potential recurrence-associated gene in colon cancer 3, it has not been validated in large prospective clinical trials or incorporated into major clinical guidelines.

Recent research has explored various long non-coding RNAs (lncRNAs) for prognostic purposes:

• A study identified LINC0219 as a vital differentially expressed gene associated with colon cancer recurrence 3
• Another study developed an 11-lncRNA signature for stage II colon cancer prognosis 4
• Research has also explored immune-related lncRNAs for predicting survival and immune landscape in colon cancer 5

However, these remain investigational approaches that require further validation before clinical implementation.

Validated Multigene Assays

Several multigene assays have undergone more extensive validation for colon cancer prognosis:

1. Oncotype DX Colon

   • Quantifies expression of 7 recurrence-risk genes and 5 reference genes 1
   • Validated in QUASAR and NSABP C-07 trials 6
   • Provides prognostic information but is not predictive of benefit from adjuvant therapy 1

2. ColoPrint

   • Quantifies expression of 18 genes 1
   • Validated in studies showing independent prognostic value 1

3. ColDx

   • Uses 634 probes to identify high-risk stage II colon cancer patients 1

Despite more extensive validation compared to LINC0219, even these multigene assays are not universally recommended. The NCCN guidelines state: "The panel believes that there are insufficient data to recommend the use of multigene assays to determine adjuvant therapy for patients with CRC" 1.

Conclusion

For monitoring colon cancer recurrence, CEA remains the only widely recommended biomarker, with measurements every 3 months for stage II and III disease for at least 3 years 2. While LINC0219 shows promise in preliminary research, it lacks the validation necessary for clinical implementation and is not mentioned in any major clinical guidelines for colorectal cancer management.

When considering biomarkers for colon cancer recurrence, clinicians should adhere to established guidelines and use validated markers like CEA while awaiting further evidence on emerging biomarkers like LINC0219.