# Biomarkers in Colorectal Cancer: Clinically Relevant Diagnostic and Prognostic Molecular Features, and the Future of Precision Medicine

**Authors:** Rebecca Whitmer, Julia Sepulveda, Jason Gandhi, Isha Puri, Rohan Gupta

PMC · DOI: 10.3390/jpm16030132 · 2026-02-28

## TL;DR

This paper reviews key genetic biomarkers in colorectal cancer and their roles in diagnosis, prognosis, and targeted treatment strategies.

## Contribution

The paper provides a comprehensive overview of clinically relevant CRC biomarkers and their implications for precision medicine.

## Key findings

- Common CRC mutations include MMR deficiency, MSI, APC, TP53, KRAS, NRAS, SMAD4, PIK3CA, and BRAF.
- These biomarkers influence tumor biology, therapeutic resistance, and response to targeted therapies.
- Biomarker-driven strategies are reshaping CRC management in both early and advanced stages.

## Abstract

Colorectal cancer (CRC) is a major public health concern in the United States. It is currently the fourth most diagnosed cancer and, despite advancements in screening and treatment, the second leading cause of cancer-related deaths. Approximately 153,000 new cases are diagnosed annually, with over 53,000 deaths reported. Understanding the molecular and genetic underpinnings of CRC biomarkers plays a crucial role in diagnosis, prognosis, and treatment planning. Specific gene mutations, including MMR deficiency leading to high microsatellite instability (MSI), as well as several other common mutations in CRC, including APC, TP53, KRAS, NRAS, SMAD4, PIK3CA and BRAF, provide valuable insights into tumor biology, therapeutic resistance, and response to targeted therapies. This review explores the mutations and co-mutations most relevant to CRC, their prevalence, prognostic significance, and implications for precision oncology. By focusing on these genetic and epigenetic alterations, we aim to contextualize how biomarker-driven strategies are reshaping the management of CRC in both early and advanced disease settings.

## Linked entities

- **Genes:** MRC1 (mannose receptor C-type 1) [NCBI Gene 4360], msi (musashi) [NCBI Gene 43087], APC (APC regulator of Wnt signaling pathway) [NCBI Gene 324], TP53 (tumor protein p53) [NCBI Gene 7157], KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845], NRAS (NRAS proto-oncogene, GTPase) [NCBI Gene 4893], SMAD4 (SMAD family member 4) [NCBI Gene 4089], PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290], BRAF (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 673]
- **Diseases:** colorectal cancer (MONDO:0005575), CRC (MONDO:0005575)

## Full-text entities

- **Genes:** AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, WEE1 (WEE1 G2 checkpoint kinase) [NCBI Gene 7465] {aka WEE1A, WEE1hu}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, MSH6 (mutS homolog 6) [NCBI Gene 2956] {aka GTBP, GTMBP, HNPCC5, HSAP, LYNCH5, MMRCS3}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, MLH1 (mutL homolog 1) [NCBI Gene 4292] {aka COCA2, FCC2, HNPCC, HNPCC2, LYNCH2, MLH-1}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290] {aka CCM4, CLAPO, CLOVE, CWS5, HMH, MCAP}, SMAD4 (SMAD family member 4) [NCBI Gene 4089] {aka DPC4, JIP, MADH4, MYHRS}, PMS2 (PMS1 homolog 2, mismatch repair system component) [NCBI Gene 5395] {aka HNPCC4, LYNCH4, MLH4, MMRCS4, PMS-2, PMSL2}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, APC (APC regulator of Wnt signaling pathway) [NCBI Gene 324] {aka BTPS2, DESMD, DP2, DP2.5, DP3, GS}, HRAS (HRas proto-oncogene, GTPase) [NCBI Gene 3265] {aka C-BAS/HAS, C-H-RAS, C-HA-RAS1, CTLO, H-RASIDX, HAMSV}, NRAS (NRAS proto-oncogene, GTPase) [NCBI Gene 4893] {aka ALPS4, CMNS, N-ras, NCMS, NRAS1, NS6}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, BRAF (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 673] {aka B-RAF1, B-raf, BRAF-1, BRAF1, NS7, RAFB1}, MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609] {aka JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7}, MSH2 (mutS homolog 2) [NCBI Gene 4436] {aka COCA1, FCC1, HNPCC, HNPCC1, LCFS2, LYNCH1}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}
- **Diseases:** UC (MESH:D003093), dysplasia (MESH:D015792), deaths (MESH:D003643), somatic disease (MESH:D013001), injury to (MESH:D014947), oncogenes (MESH:D000074723), Tumor (MESH:D009369), bleeding (MESH:D006470), Blood Disorders (MESH:D006402), obesity (MESH:D009765), metabolic syndrome (MESH:D024821), MMR deficiencies (MESH:C536928), inflammation (MESH:D007249), polyposis (MESH:D044483), MSI (MESH:D053842), liver (MESH:D017093), disease (MESH:D004194), Hereditary syndromes (MESH:D009386), cytotoxic (MESH:D064420), Adenomatous polyposis coli (MESH:D011125), adenoma-carcinoma (MESH:D000230), adenomas (MESH:D000236), metastases (MESH:D009362), CRC (MESH:D015179)
- **Chemicals:** ipilimumab (MESH:D000074324), oxaliplatin (MESH:D000077150), Pembrolizumab (MESH:C582435), nivolumab (MESH:D000077594), alpelisib (MESH:C585539), aspirin (MESH:D001241), 5-FU, leucovorin, and oxaliplatin (-), panitumumab (MESH:D000077544), alcohol (MESH:D000438), Sotorasib (MESH:C000706028), cetuximab (MESH:D000068818), adavosertib (MESH:C549567), 5-FU (MESH:D005472), Bevacizumab (MESH:D000068258), FOLFOX (MESH:C410216), capecitabine (MESH:D000069287), encorafenib (MESH:C000601108)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** H1047L, E542K, serine/threonine, D594G, V600, G12D, Q61R, V600E substitution at codon 600, G12C, E545K, Q61K

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Source: https://tomesphere.com/paper/PMC13027939