Identification of circulating protein biomarkers for pancreatic cancer cachexia
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ABSTRACT:
PROVIDER: PRJNA489371 | ENA |
REPOSITORIES: ENA
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Project description:Over 80% of patients with pancreatic ductal adenocarcinoma (PDAC) suffer from cachexia, characterized by severe muscle and fat loss and yet, there are no biomarkers identified for this debilitating condition. Our objective was to identify circulating protein biomarkers using serum for human PDAC cachexia and understand their biological functions. Serum from 30 patients with PDAC was collected and protein profiles were generated using SOMAscan. The protein profiles were correlated with clinical variables such as Cancer associated weight loss (CAWL), body composition measurements of skeletal muscle index (SMI), skeletal muscle density (SMD), total adipose index (TAI) using Spearman’s correlation. Overall, 110 proteins of 1294 correlated with these clinical measures - 47 proteins for CAWL, 19 for SMI, 14 for SMD, and 30 for TAI (r-value 0.5, p<0.05). LYVE1, a homolog of CD44 implicated in tumor metastasis, was the top CAWL-associated protein (r= 0.67, p=0.0001). Protein co-expression network analysis identified immune system related pathways such as B-cell signaling, natural killer cell signaling, IL6 signaling in addition to identifying other known pathways in cachexia. Taken together, these data identify both immune system molecules and additional secreted factors and pathways not previously associated with PDAC and confirm the activation of previously identified pathways.
2020-12-31 | GSE119483 | GEO
Project description:Pancreatic cancer is characterized by a high frequency of cachexia, pain and neural invasion (N-inv). Neural damage is occurred by N-inv and modulates pain and muscle atrophy via the activation of astrocyte in the connected spine. The activated astrocyte by N-inv, thus, may affect cachexia in pancreatic cancer. Clinical studies in patients and autopsy cases with pancreatic cancer have revealed that N-inv is related to cachexia and astrocytic activation. We established a novel murine model of cancer cachexia using N-inv of human pancreatic cancer cells. Mice with N-inv showed a loss of body weight, skeletal muscle, and fat mass without appetite loss, which are compatible with an animal model of cancer cachexia. Activation of astrocytes in the spinal cord connected with N-inv was observed in our model. Experimental cachexia was suppressed by disrupting neural routes or inhibiting the activation of astrocytes. These data provide the first evidence that N-inv induces cachexia via astrocytic activation of neural route in pancreatic cancer. We produced neural invasion (N-inv) model using intraneural injection of Capan-1 cells to left sciatic nerve of male SCID mouse. For controls, subcutaneous model (SC) and PBS model were produced. Microarray analysis was performed using the first lumbar cord (L1) from PBS, SC, and N-inv mice at 6 w (n = 2 each).
2011-12-07 | E-GEOD-34189 | biostudies-arrayexpress
Project description:Pancreatic cancer is characterized by a high frequency of cachexia, pain and neural invasion (N-inv). Neural damage is occurred by N-inv and modulates pain and muscle atrophy via the activation of astrocyte in the connected spine. The activated astrocyte by N-inv, thus, may affect cachexia in pancreatic cancer. Clinical studies in patients and autopsy cases with pancreatic cancer have revealed that N-inv is related to cachexia and astrocytic activation. We established a novel murine model of cancer cachexia using N-inv of human pancreatic cancer cells. Mice with N-inv showed a loss of body weight, skeletal muscle, and fat mass without appetite loss, which are compatible with an animal model of cancer cachexia. Activation of astrocytes in the spinal cord connected with N-inv was observed in our model. Experimental cachexia was suppressed by disrupting neural routes or inhibiting the activation of astrocytes. These data provide the first evidence that N-inv induces cachexia via astrocytic activation of neural route in pancreatic cancer.
2011-12-07 | GSE34189 | GEO
Project description:More than 85% of patients with pancreatic ductal adenocarcinoma (PDAC) suffer from cachexia, a debilitating syndrome characterized by loss of muscle and fat. To model PDAC cachexia in mice, 12-week-old C57BL/6J male mice were implanted with the cachexia inducing pancreatic cell line, KPC32908, into the pancreas. Controls underwent a sham surgery. Mice were euthanized under isoflurane anesthesia when the tumor-bearing mice exhibited cachexia, including ~18% loss of quadriceps mass versus sham controls. Quadriceps muscle was flash frozen at euthanasia. 1mg quadriceps protein lysate per sample was used for kinome profiling.
2025-04-21 | PXD047411 | Pride
Project description:Cancer cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and it is one of the most frequent causes of death. Severe wasting accounts for more than 80% in patients with advanced pancreatic cancer. Here we wanted to define, by using an microarray approach and the Pdx1-cre;LSL-KrasG12D;INK4a/arffl/fl, the pathways involved in muscle, liver and white adipose tissue wasting. The aim of our work was to characterize as extensively as possible the pathways activated by the pancreatic cancer-induced cachectic tissues. For this purpose, we generated and compared genome-wide expression profiles of white adipose tissue, skeletal muscle and liver, from Pdx1-cre;LSL-KrasG12D;INK4a/arffl/fl and LSL-KrasG12D;INK4a/arffl/fl mice at 10 weeks-old. Tissue samples by triplicate was obtained from liver, muscle and adipose tissues in both groups, controls and cachectic mice. Total RNA samples was processed and profiled on Affymetrix Mouse Gene 1.0 ST arrays as previously described (Cano et al, 2012)
2014-01-10 | E-GEOD-51931 | biostudies-arrayexpress
Project description:Cancer cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and it is one of the most frequent causes of death. Severe wasting accounts for more than 80% in patients with advanced pancreatic cancer. Here we wanted to define, by using an microarray approach and the Pdx1-cre;LSL-KrasG12D;INK4a/arffl/fl, the pathways involved in muscle, liver and white adipose tissue wasting.
2014-01-10 | GSE51931 | GEO
Project description:Cachexia frequently develops in patients with pancreatic ductal adenocarcinoma (PDAC) and contributes to cancer deaths.Sex differences have been observed in cancer cachexia; however, the underlying molecular mechanisms are far less addressed. We assessed sex difference in PDAC cachexia phenotypes in the KPC (Kras-G12D;Trp-R172H;Pdx1::Cre) genetically engineered mouse model of PDAC and profiled gene expression in the quadriceps skeletal muscles. Males with PDAC experienced earlier cachexia-onset than the female counterpart and activin blockade by ACVR2B/Fc reduced cachexia sympotomes in males but not females. PDAC induced earlier global transcritome alterations in males than females.
2022-05-10 | GSE157251 | GEO
Project description:The evaluation of exosomal miRNA biomarkers for cachexia
| PRJNA915348 | ENA
Project description:The aim of the study is to test if Gemcitabine in combination with nab-paclitaxel can prevent muscle wasting and cardiac dysfunction in a mouse model of pancreatic cancer cachexia.
2025-04-04 | GSE234545 | GEO
Project description:In order to screen miRNAs related to cachexia, we collected plasma from patients with gastric cancer cachexia or without cachexia, and extracted exosomes from plasma. Then, we analyzed the gene expression profile of 3 gastric cancer patients with cachexia and 2 gastric cancer patients with non cachexia.
2024-12-23 | GSE221666 | GEO