Identification of circulating protein biomarkers for pancreatic cancer cachexia

Shahda, Safi; Narasimhan, Ashok; Kays, Joshua K.; Perkins, Susan M.; Cheng, Lijun; Hannaford, Katheryn N.; Schloss, Daniel; Koniaris, Leonidas G.; Zimmers, Teresa A.

doi:10.1101/359661

Cited by 2 publications

(2 citation statements)

References 38 publications

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“…The study was conducted under the Indiana University Institutional Review Board (IRB) approved protocol #1312105608, the same protocol referenced in our prior study [ 61 ]. Patients were recruited at Indiana University Hospital between 2014 and 2016.…”

Section: Methodsmentioning

confidence: 99%

Profiling of Adipose and Skeletal Muscle in Human Pancreatic Cancer Cachexia Reveals Distinct Gene Profiles with Convergent Pathways

Narasimhan

Zhong

et al. 2021

Cancers

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The vast majority of patients with pancreatic ductal adenocarcinoma (PDAC) suffer cachexia. Although cachexia results from concurrent loss of adipose and muscle tissue, most studies focus on muscle alone. Emerging data demonstrate the prognostic value of fat loss in cachexia. Here we sought to identify the muscle and adipose gene profiles and pathways regulated in cachexia. Matched rectus abdominis muscle and subcutaneous adipose tissue were obtained at surgery from patients with benign conditions (n = 11) and patients with PDAC (n = 24). Self-reported weight loss and body composition measurements defined cachexia status. Gene profiling was done using ion proton sequencing. Results were queried against external datasets for validation. 961 DE genes were identified from muscle and 2000 from adipose tissue, demonstrating greater response of adipose than muscle. In addition to known cachexia genes such as FOXO1, novel genes from muscle, including PPP1R8 and AEN correlated with cancer weight loss. All the adipose correlated genes including SCGN and EDR17 are novel for PDAC cachexia. Pathway analysis demonstrated shared pathways but largely non-overlapping genes in both tissues. Age related muscle loss predominantly had a distinct gene profiles compared to cachexia. This analysis of matched, externally validate gene expression points to novel targets in cachexia.

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Section: Methodsmentioning

confidence: 99%

Profiling of Adipose and Skeletal Muscle in Human Pancreatic Cancer Cachexia Reveals Distinct Gene Profiles with Convergent Pathways

Narasimhan

Zhong

et al. 2021

Cancers

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“…Physical exercise is able to increase FABP3 circulating levels [21] and its mRNA in skeletal muscle [22]. Moreover, circulating levels of FABP3 have been inversely associated with skeletal muscle attenuation (or skeletal muscle density) in patients with pancreatic cancer and cachexia [23], but a direct correlation with cachexia is still missing.…”

Section: Introductionmentioning

confidence: 99%

Myokines in treatment-naïve patients with cancer-associated cachexia

et al. 2021

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Cancer-associated cachexia is a complex metabolic syndrome characterized by weight loss and systemic inflammation. Muscle loss and fatty infiltration into muscle are associated with poor prognosis in cancer patients. Skeletal muscle secretes myokines, factors with autocrine, paracrine and/or endocrine action, which may be modified by or play a role in cachexia. This study examined myokine content in the plasma, skeletal muscle and tumor homogenates from treatment-naïve patients with gastric or colorectal stages I-IV cancer with cachexia (CC, N ¼ 62), or not (weight stable cancer, WSC, N ¼ 32). Myostatin, interleukin (IL) 15, follistatin-like protein 1 (FSTL-1), fatty acid binding protein 3 (FABP3), irisin and brain-derived neurotrophic factor (BDNF) protein content in samples was measured with Multiplex technology; body composition and muscle lipid infiltration were evaluated in computed tomography, and quantification of triacylglycerol (TAG) in the skeletal muscle. Cachectic patients presented lower muscle FSTL-1 expression (p ¼ 0.047), higher FABP3 plasma content (p ¼ 0.0301) and higher tumor tissue expression of FABP3 (p ¼ 0.0182), IL-15 (p ¼ 0.007) and irisin (p ¼ 0.0110), compared to WSC. Neither muscle TAG content, nor muscle attenuation were different between weight stable and cachectic patients. Lumbar adipose tissue (AT) index, visceral AT index and subcutaneous AT index were lower in CC (p ¼ 0.0149, p ¼ 0.0455 and p ¼ 0.0087, respectively), who also presented lower muscularity in the cohort (69.2% of patients; p ¼ 0.0301), compared to WSC. The results indicate the myokine profile in skeletal muscle, plasma and tumor is impacted by cachexia. These findings show that myokines eventually affecting muscle wasting may not solely derive from the muscle itself (as the tumor also may

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Identification of circulating protein biomarkers for pancreatic cancer cachexia

Abstract: Background: Over 80% of patients with pancreatic ductal adenocarcinoma (PDAC) suffer

Cited by 2 publications

References 38 publications

Profiling of Adipose and Skeletal Muscle in Human Pancreatic Cancer Cachexia Reveals Distinct Gene Profiles with Convergent Pathways

Profiling of Adipose and Skeletal Muscle in Human Pancreatic Cancer Cachexia Reveals Distinct Gene Profiles with Convergent Pathways

Myokines in treatment-naïve patients with cancer-associated cachexia

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