The Role of Metabolomics in Pre-operative,Peri-operative, and Post-operative Phases in Patients with Colon Cancer: A Comparative Analysis of Biomarker changes and short-term clinical outcomes.

Introduction: Colon cancer (CC) ranks fourth among all cancers globally and fifth leading cause

of cancer-related mortality, with 1,142,286 new cases reported in 2022 according to

GLOBOCAN- 2022(1). Worldwide, the age-standardized incidence rate (ASIR) of colon cancer

was 10.7 cases per 100,000 people with higher incidence in men. Colon cancer is responsible

for 538,167 deaths globally (2) . High-income countries (HIC) exhibit higher ASIR of 5.8 to 32.7

with median of 17.5, whereas South Asian countries have ASIR of 1.7 to 22.7 with median of

7.1. Colon cancer (ICD-10: C18) is becoming a growing health challenge in India. In 2022, the

country recorded 45,697 new cases, representing 4.1% of all cancer diagnoses. CC ranks 8th

among males and 10th among females in India, with higher incidence observed in Metro cities.

Though ASIR in India is 3.6 per 100,000 population, much lower than in HIC, the disease shows

a concerning gender disparity: 4.2 in males versus 3.0 in females. Alarming rise in CC in India

is due to shift towards processed foods, reduced physical activity, and Western-style diets rich

in red meat but poor in fibre and lifestyle factors like smoking. Increased susceptibility of CC in

younger population is attributed to genetic factors, growing obesity rates, and environmentaltoxins like pesticides(3,4). Lower prevalence of CC in India could be potentially due to

underreporting, late- stage diagnoses and inadequate healthcare infrastructure leading to

mortality which further emphasize on urgent need for awareness campaigns and screening

programs tailored to India’s unique cancer profile. The diagnostic modality for CC varies,

ranging from non-invasive stool-based tests like faecal occult blood test and faecal

immunochemical test (FIT), to advanced imaging techniques such as CT colonography.

Colonoscopy is still considered as the gold standard for both screening and diagnosis, offering

high sensitivity and specificity.(5) . Several non-invasive serum biomarkers have been used for

diagnosis and screening. Carcinoembryonic antigen (CEA), glycoprotein expressed by

epithelial tumours is elevated in 70% of CC. At a cut-off of 5 ng/mL CEA has specificity of 90%

and sensitivity of 64%, helping in diagnosis and monitoring of therapy. Other markers helpful in

diagnosis and monitoring of CC include- Tissue polypeptide specific antigen (TPS), Tumour

associated glycoprotein 72(TAG -72), Macrophase colony stimulating factor (M- CSF),

interleukin – 6 and Alcohol dehydrogenase isoenzymes. (6). CC treatment is stage-dependent

and multimodal inclusive of surgery, chemotherapy, targeted therapies, and immunotherapy

depending on spread of disease. Emerging approaches, including ctDNA-guided treatment and

microbiota-based therapies, are under investigation to personalize care.

The draw back with current serum biomarkers such as CEA are lesser sensitivity in early-stage

disease and failure to provide real-time insights into tumour metabolism or surgical stress

responses. Metabolomics, the systematic study of small-molecule metabolites, captures

dynamic biochemical alterations in biofluids (serum, urine) and tissues, thereby can reveal

disease- specific signatures associated with tumour progression, therapeutic response, and

postoperative recovery. Colonic cancer associated metabolic dysregulations of glycolysis

(Warburg effect), TCA cycle and amino acid metabolism are well documented.(7,8). A

comprehensive metabolomic analysis across pre-, intra-, and post-treatment stages in CC

patients may elucidate the temporal dynamics of metabolites and its association with disease

progression, therapeutic response.