Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide despite remarkable advances in its diagnosis and treatment. Current therapeutic approaches, including surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy, have significantly improved survival in both localized and advanced disease. However, metastatic CRC continues to be associated with poor long-term outcomes due to delayed diagnosis, tumor heterogeneity, therapeutic resistance, treatment-related toxicity, and high healthcare costs. Consequently, there is an increasing need for reliable biomarkers that can facilitate early detection, accurate prognosis, prediction of therapeutic response, and personalized treatment strategies. Recent developments in genomics, epigenomics, transcriptomics, and molecular pathology have accelerated the discovery of novel biomarkers for colorectal cancer. Among the clinically established biomarkers, alterations in KRAS, NRAS, BRAF, and microsatellite instability (MSI) status have become integral to treatment selection and precision oncology. Nevertheless, relatively few biomarkers have achieved routine clinical implementation, emphasizing the need for continued biomarker discovery and rigorous clinical validation. Emerging evidence suggests that non-coding RNAs, particularly long non-coding RNAs (lncRNAs), play critical roles in colorectal cancer initiation, progression, metastasis, and therapeutic resistance. This review comprehensively summarizes the literature published up to Feb 2023 on established and emerging protein-, DNA-, RNA-, and liquid biopsy- based biomarkers for colorectal cancer. Particular emphasis is placed on plasmacytoma variant translocation 1 (PVT1), an oncogenic lncRNA that has demonstrated significant potential as a diagnostic, prognostic, and predictive biomarker. The molecular mechanisms through which PVT1 regulates colorectal cancer progression, metastasis, and chemoresistance are critically discussed, together with its potential as a therapeutic target. Furthermore, this review highlights current challenges, research gaps, and future perspectives in biomarker- guided precision medicine, providing a comprehensive reference for researchers and clinicians working toward improved diagnosis, individualized therapy, and better clinical outcomes in colorectal cancer.

Colorectal cancer, Biomarkers, Precision medicine, Early diagnosis, Prognostic biomarkers, Predictive biomarkers, Long non-coding RNA (lncRNA), PVT1, KRAS, EGFR, Molecular biomarkers