Study on the Pathogenesis and Reversal Strategies of Cancer Cachexia Based on Multi-Omics (PRCC-MO)

Cancer cachexia is a complex systemic metabolic syndrome with high incidence and mortality rates, significantly impacting the prognosis and survival of cancer patients.Current clinical comprehensive intervention approaches can only provide transient symptom relief and fail to fundamentally block or reverse muscle and fat loss. The core challenge lies in the extreme complexity of this pathological mechanism and the lack of early biomarkers.To overcome the limitations of traditional single-dimensional research approaches, this study proposes a combined analysis method utilizing "multi-omics" (imaging omics, pathological omics, metabolomics, and metagenomics) to construct a panoramic systemic model spanning macroscopic clinical manifestations and microscopic molecular processes. The aim is to comprehensively elucidate the pathogenesis and metabolic pathways of cachexia, thereby precisely identifying potential therapeutic targets capable of reversing this pathological process.

Study Overview

• Status: Recruiting
• Conditions: Cachexia; Cancer; Sarcopenia
• Intervention / Treatment: Other: Administration of placebo as a negative control to validate experimental efficacy; Drug: Standard nutritional intervention was administered as a positive control to validate experimental efficacy.; Drug: Validation of intervention efficacy through enhanced intervention in nutritionally high-risk patients

Detailed Description

Cancer cachexia is a multifactorial metabolic syndrome characterized by persistent skeletal muscle atrophy, with or without loss of adipose tissue. It differs from conventional malnutrition, for which conventional nutritional support often fails to fully reverse its progression. Cachexia has an extremely high incidence rate in patients with advanced cancer, with an overall prevalence ranging from approximately 50% to 80%. Especially in malignant tumors of the digestive system such as gastric cancer, colorectal cancer, and pancreatic cancer, the incidence of cachexia is higher due to direct involvement of digestive organs by tumors, and the disease prognosis is often more severe. Existing medical evidence indicates that cancer cachexia is closely associated with poor prognosis. Cachexia not only leads to a sharp decline in physical condition and impairment of quality of life, but also significantly reduces tolerance to chemotherapy, radiotherapy, and surgery, while increasing treatment-related toxic side effects. According to statistics, approximately 20% to 30% of cancer-related deaths are not directly attributable to increased tumor burden, but rather to cardiopulmonary failure and metabolic collapse caused by cachexia. Therefore, controlling and reversing cachexia is a critical step in prolonging survival and improving treatment outcomes.

At present, clinical treatment of cancer cachexia does not rely on a single approach but rather tends to adopt a "multimodal comprehensive intervention strategy." Specifically, this strategy encompasses enhanced nutritional support therapy (such as providing high-protein, high-calorie enteral/parenteral nutrition formulations), pharmacological interventions (including the use of progestogens to improve appetite and nonsteroidal anti-inflammatory drugs to counter systemic inflammatory responses), and targeted rehabilitation physical training, aiming to maintain functional status through a multidisciplinary approach. However, it must be acknowledged that despite the implementation of the aforementioned comprehensive measures, significant limitations in clinical efficacy remain. In clinical practice, these interventions often only provide temporary symptomatic relief to a limited extent (e.g., short-term improvement in appetite or slowing of weight loss rate), but fail to fundamentally block the "molecular switch" underlying skeletal muscle protein degradation, nor can these interventions effectively reverse already established muscle atrophy and functional decline. The fundamental reason for this dilemma lies in the extreme complexity of the pathogenesis of cachexia. Cachexia is not merely "malnutrition," but rather a "metabolic storm" involving abnormal regulation of multiple organs (muscle, adipose tissue, liver, intestine, etc.) and systems (immune, neuroendocrine, metabolic) throughout the body. Current treatments often only address downstream symptoms without correcting the complex upstream molecular dysregulation. More critically, there is currently an extreme lack of in-depth understanding of the early activation mechanisms of cachexia in clinical practice, and no reliable, high-sensitivity biomarkers (such as specific blood parameters or imaging features) are available. This results in the vast majority of patients being diagnosed with cachexia when the body is already in a severe catabolic state (resistant phase), thereby missing the optimal time window for early intervention and disease reversal.

Cancer cachexia is essentially a highly complex systemic metabolic disorder syndrome, with core pathology stemming from extensive and profound abnormal interactions between tumors and the host. These interactions are not confined to the tumor site but also trigger multi-organ functional remodeling, including skeletal muscle and adipose tissue, through inflammatory mediators and metabolic products. In past medical explorations, traditional research models were often confined to single-dimensional observations. This "panoramic view through a tube" approach struggled to reveal the intrinsic connections between macroscopic signs and microscopic molecular mechanisms during the development of cachexia. In recent years, with the advancement of high-throughput biotechnology, "multi-omics" integrated analysis has become a key approach for deciphering such complex diseases. This study aims to overcome traditional limitations by innovatively constructing a panoramic systemic model: the investigators will utilize imaging omics to deeply mine muscle mass and fat infiltration characteristics invisible to the naked eye in CT data, combine pathological omics to observe tumor microenvironment-induced pathological remodeling at the cellular level, simultaneously employ metabolomics to track metabolic dynamic fingerprints in blood and feces, and apply metagenomics to analyze the microecological composition of the "gut-muscle axis." Through this deep integration spanning macro and micro levels, structure and function, the investigators aim to map a comprehensive molecular atlas of cachexia onset and progression, thereby precisely identifying therapeutic targets capable of reversing this pathological process. This multi-level cross-disciplinary research enables the field to transcend the limitations of traditional perspectives, revealing a comprehensive mechanism by which tumors induce muscle and fat loss through altering metabolic environments, reshaping gut microbiota, and inducing histopathological changes-from macroscopic alterations in body composition to microscopic molecular metabolic pathways.

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hanwen Liu; Phone Number: +86 18941960007; Email: X18941960007@126.com
• Study Contact Backup: Name: XiaoXu Liu; Phone Number: +86 18042901898; Email: X18941960007@126.com

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China
      • Recruiting
      • The First Affiliated Hospital of China Medical University
      • Contact: Kai Li; Phone Number: +86 18941960007; Email: cmu_likai@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Signed informed consent form and voluntary participation in this study
• Histologically and/or cytologically confirmed diagnosis of cancer
• Patients with gastrointestinal malignancies, including:
• Esophageal cancer
• Hepatocellular carcinoma
• Gastric cancer
• Cholangiocarcinoma
• Patients undergoing histopathological examination of primary lesion biopsy or gastrointestinal endoscopic biopsy

Exclusion Criteria:

• Pregnant or lactating women
• Presence of contraindications to surgery
• Cognitive dysfunction, psychiatric disorders, impaired consciousness, or inability/unwillingness to cooperate
• Presence of two or more concurrent primary tumors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: No nutritional intervention; No intervention was applied as a negative control to validate the experimental effect.	Other: Administration of placebo as a negative control to validate experimental efficacy; Administration of placebo as a negative control to validate experimental efficacy
Active Comparator: Standard Nutritional Intervention; Standard intervention was administered as a positive control to validate experimental efficacy.	Drug: Standard nutritional intervention was administered as a positive control to validate experimental efficacy.; Standard nutritional intervention was administered as a positive control to validate experimental efficacy.
Active Comparator: Enhanced Nutritional Intervention; Validation of intervention efficacy through enhanced intervention in nutritionally high-risk patients	Drug: Validation of intervention efficacy through enhanced intervention in nutritionally high-risk patients; Validation of intervention efficacy through enhanced intervention in nutritionally high-risk patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in skeletal muscle index (SMI, cm²/m²)	Skeletal muscle index (SMI) is calculated from cross-sectional CT images at the third lumbar vertebra (L3) level and normalized by height (cm²/m²).	Baseline to 12 months (assessed at 1, 3, 6, and 12 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum albumin (g/L)	Serum albumin level measured using standard laboratory methods.	Baseline to 12 months (assessed at 1, 3, 6, and 12 months)
Change in C-reactive protein (CRP, mg/L)	CRP levels measured as a marker of systemic inflammation.	Baseline to 12 months (assessed at 1, 3, 6, and 12 months)
Change in handgrip strength (kg)	Handgrip strength measured using a calibrated dynamometer.	Baseline to 12 months (assessed at 1, 3, 6, and 12 months)
Change in gait speed (m/s)	Gait speed assessed using a standardized walking test.	Baseline to 12 months (assessed at 1, 3, 6, and 12 months)
Change in visceral adipose tissue area (cm²)	Visceral fat area quantified from CT images at the L3 level.	Baseline to 12 months (assessed at 1, 3, 6, and 12 months)
Change in subcutaneous adipose tissue area (cm²)	Subcutaneous fat area quantified from CT images at the L3 level.	Baseline to 12 months (assessed at 1, 3, 6, and 12 months)
Change in skeletal muscle area (cm²)	Skeletal muscle area measured from CT images at the L3 level.	Baseline to 12 months (assessed at 1, 3, 6, and 12 months)

Collaborators and Investigators

• Sponsor: China Medical University, China

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2026
• Primary Completion (Estimated): March 20, 2028
• Study Completion (Estimated): March 20, 2028

Study Registration Dates

• First Submitted: March 18, 2026
• First Submitted That Met QC Criteria: April 2, 2026
• First Posted (Actual): April 9, 2026

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: cancer associated cachexia; Multi-omics Integrated Analysis; Mechanism Exploration and Reversal Strategy Research
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Body Weight; Body Weight Changes; Muscular Atrophy; Atrophy; Weight Loss; Thinness; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neoplasms; Sarcopenia; Cachexia
• Other Study ID Numbers: 2026-124-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No