Cachexia is Prevalent in Patients With Hepatocellular Carcinoma and Associated With Worse Prognosis

Olaechea

J cachexia sarcopenia muscle

et al. 2022

Self Cite

Background Cancer cachexia is frequently documented by self‐reported, single time‐point weight histories. This approach lacks the granularity needed to fully elucidate the progression of cachexia syndrome. This study aimed to longitudinally assess body weight changes pre‐ and post‐cancer diagnosis in gastrointestinal (GI) cancer patients. Methods Body weights and relevant clinical data recorded in the electronic health record 12 months pre‐ and post‐GI cancer (colorectal, gastroesophageal, hepatobiliary and pancreatic) diagnosis were extracted. Weight loss was categorized by the International Consensus Definition for cachexia. Results A total of 879 patients were included in the final cohort including patients diagnosed with colorectal (n = 317), hepatocellular (n = 185), biliary (n = 72), pancreatic (n = 186) or gastroesophageal (n = 119) cancer. Stage of disease was equally distributed. Patients without cachexia at diagnosis (n = 608) remained weight stable during the 12 months pre‐diagnosis (+0.5 ± 0.5% body weight; P = 0.99). Patients with cachexia at diagnosis (n = 271) remained weight stable 6 to 12 months prior to diagnosis (+0.4 ± 0.8%; P > 0.9999) and lost 8.7 ± 0.6% (P < 0.0001) within the 6 months pre‐diagnosis. Patients without cachexia at diagnosis lost more weight post‐diagnosis (6.3 ± 0.6%) than patients with cachexia at diagnosis (4.7 ± 1.0%; P = 0.01). Pre‐diagnosis weight trajectories did not differ between primary malignancies or stage of disease in patients without or with cachexia at diagnosis (all P ≥ 0.05). Post‐diagnosis weight trajectories did differ by primary malignancy (P ≤ 0.0002) and stage (P < 0.0001). In both patients without and with cachexia at diagnosis, colorectal patients lost the least amount of weight post‐diagnosis and gastroesophageal patients lost the most amount of weight post‐diagnosis. Stage 4 patients without or with cachexia at diagnosis lost the most weight post‐diagnosis (P ≤ 0.0003). Regardless of cachexia status at diagnosis, patients lost more weight when treated with systemic therapy (7.1 ± 0.7%; P < 0.0001; n = 419) or radiation therapy (8.4 ± 1.4%; P = 0.02; n = 116) compared to those who did not. Patients who did not have surgery lost more weight post‐diagnosis (7.6 ± 1.1%; P < 0.0001; n = 355) compared to those who did have surgery. By 12 months post‐diagnosis, 83% of the surviving GI cancer patients in this cohort had transitioned into cachexia syndrome. Conclusions Significant weight loss in patients with GI cancer cachexia at diagnosis initiates at least 6 months prior to diagnosis, and most patients will transition into cachexia syndrome post‐diagnosis, regardless of pre‐diagnosis weight change and stage of disease. These findings punctuate the importance of weight surveillance in cancer detection and earlier palliative interventions post‐diagnosis in the GI cancer patient population.

Section: Resultssupporting

confidence: 82%

Section: Resultsmentioning

confidence: 71%

A preponderance of gastrointestinal cancer patients transition into cachexia syndrome

Olaechea

J cachexia sarcopenia muscle

et al. 2022

Self Cite

“…Studies have shown that the cachexia of cancer affects the quality of life of many patients with advanced cancer [ 32 ]. Cachexia is prevalent in patients with HCC and associated with worse prognosis, which develops in approximately 25% of HCC patients during the disease course [ 33 ]; however, cachexia is considered a covariate also need to further study. In this manuscript, we used bioinformatics to determine prognosis-related molecular subtypes of HCC using four public datasets.…”

Section: Discussionmentioning

confidence: 99%

Prognosis-Related Molecular Subtypes and Immune Features Associated with Hepatocellular Carcinoma

Lin

Gao

et al. 2022

Cancers

Bioinformatics tools were used to identify prognosis-related molecular subtypes and biomarkers of hepatocellular carcinoma (HCC). Differential expression analysis of four datasets identified 3330 overlapping differentially expressed genes (DEGs) in the same direction in all four datasets. Those genes were involved in the cell cycle, FOXO signaling pathway, as well as complement and coagulation cascades. Based on non-negative matrix decomposition, two molecular subtypes of HCC with different prognoses were identified, with subtype C2 showing better overall survival than subtype C1. Cox regression and Kaplan-Meier analysis showed that 217 of the overlapping DEGs were closely associated with HCC prognosis. The subset of those genes showing an area under the curve >0.80 was used to construct random survival forest and least absolute shrinkage and selection operator models, which identified seven feature genes (SORBS2, DHRS1, SLC16A2, RCL1, IGFALS, GNA14, and FANCI) that may be involved in HCC occurrence and prognosis. Based on the feature genes, risk score and recurrence models were constructed, while a univariate Cox model identified FANCI as a key gene involved mainly in the cell cycle, DNA replication, and mismatch repair. Further analysis showed that FANCI had two mutation sites and that its gene may undergo methylation. Single-sample gene set enrichment analysis showed that Th2 and T helper cells are significantly upregulated in HCC patients compared to controls. Our results identify FANCI as a potential prognostic biomarker for HCC.

“…Its complex clinical symptoms affect more than 50% of patients with cancer and 60–80% of patients with advanced cancer and causes the death of at least 20% of patients with cancer. 34 The incidence of cachexia varies with tumor type 21 , 22 , 23 (Table 1 ), and the factors leading to changes are unclear, which may be closely related to tumor stage, sex and age of patients, genetic risk factors, complications, and treatment response. The prevalence of cancer cachexia may be related to patient genotype, and some candidate genes have been used in exploring and elucidating individual differences in cachexia susceptibility.…”

Section: Clinical Characteristics Of Cancer Cachexiamentioning

confidence: 99%

Targeting cancer cachexia: Molecular mechanisms and clinical study

Wang

Lin

et al. 2022

MedComm

Cancer cachexia is a complex systemic catabolism syndrome characterized by muscle wasting. It affects multiple distant organs and their crosstalk with cancer constitute cancer cachexia environment. During the occurrence and progression of cancer cachexia, interactions of aberrant organs with cancer cells or other organs in a cancer cachexia environment initiate a cascade of stress reactions and destroy multiple organs including the liver, heart, pancreas, intestine, brain, bone, and spleen in metabolism, neural, and immune homeostasis. The role of involved organs turned from inhibiting tumor growth into promoting cancer cachexia in cancer progression. In this review, we depicted the complicated relationship of cancer cachexia with the metabolism, neural, and immune homeostasis imbalance in multiple organs in a cancer cachexia environment and summarized the treatment progress in recent years. And we discussed the molecular mechanism and clinical study of cancer cachexia from the perspective of multiple organs metabolic, neurological, and immunological abnormalities. Updated understanding of cancer cachexia might facilitate the exploration of biomarkers and novel therapeutic targets of cancer cachexia.