Prognostic and clinicopathological significance of Hapto and Gremlin1 expression in extrahepatic cholangiocarcinoma

Wu, Zhengchun; Liu, Ru‐Shi; Miao, Xiangshui; Li, Daiqiang; Zou, Qiong; Yuan, Yuan; Yang, Zhulin

doi:10.7150/jca.36886

Cited by 4 publications

(5 citation statements)

References 42 publications

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“…Then, the PSM analysis was incorporated to omit the bias selection between with mucinous and adeno CCA patients. Meanwhile the Kaplan-Meier survival analysis allowed us to determine the percentage of patients who survive a specific event ( 23 ). Before and after the PSM analysis, the patients were assessed for Kaplan-Meier survival analysis and showed no significant difference.…”

Section: Discussionmentioning

confidence: 99%

Prognostic models for mucinous and non-specific adeno cholangiocarcinoma: a population-based retrospective study

Azhar,

Zhang,

Liu

et al. 2024

Front. Endocrinol.

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BackgroundClinically, the diagnosis and treatment of cholangiocarcinoma are generally different according to the location of occurrence, and the studies rarely consider the differences between different pathological types. Cholangiocarcinomas in large- and middle-sized intrahepatic bile ducts are mostly mucinous, while in small sized bile duct are not; mucinous extrahepatic cholangiocarcinomas are also more common than mucinous intrahepatic cholangiocarcinoma. However, it is unclear whether these pathological type differences are related to the prognosis.MethodsData of total 22509 patients was analyzed from Surveillance, Epidemiology, and End Results program database out of which 22299 patients were diagnosed with common adeno cholangiocarcinoma while 210 were diagnosed with mucinous cholangiocarcinoma. Based on the propensity score matching (PSM) analysis, between these two groups’ clinical, demographic, and therapeutic features were contrasted. The data were analyzed using Cox and LASSO regression analysis and Kaplan-Meier survival curves. Ultimately, overall survival (OS) and cancer specific survival (CSS) related prognostic models were established and validated in test and external datasets and nomograms were created to forecast these patients’ prognosis.ResultsThere was no difference in prognosis between mucinous cholangiocarcinoma and adeno cholangiocarcinoma. Therefore, we constructed prognostic model and nomogram that can be used for mucinous and adeno cholangiocarcinoma at the same time. By comparing the 9 independent key characteristics i.e. Age, tumor size, the number of primary tumors, AJCC stage, Grade, lymph node status, metastasis, surgery and chemotherapy, risk scores were calculated for each individual. By integrating these two pathological types in OS and CSS prognostic models, effective prognosis prediction results could be achieved in multiple datasets (OS: AUC 0.70–0.87; CSS: AUC 0.74–0.89).ConclusionAge, tumor size, the number of primary tumors, AJCC stage, Grade, lymph node status, metastasis, surgery and chemotherapy are the independent prognostic factors in OS or CSS of the patients with mucinous and ordinary cholangiocarcinoma. Nomogram that can be used for mucinous and adeno cholangiocarcinoma at the same time is of significance in clinical practice and management of cholangiocarcinoma.

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Section: Discussionmentioning

confidence: 99%

Prognostic models for mucinous and non-specific adeno cholangiocarcinoma: a population-based retrospective study

Azhar,

Zhang,

Liu

et al. 2024

Front. Endocrinol.

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“…The effect of GREM1 on the prognosis of malignant tumors remains elusive. Some studies have linked high GREM1 expression to poor prognosis in several malignancies, including ER-negative breast cancer [ 16 ], cervical cancer [ 61 ], ex-trahepatic cholangiocarcinoma [ 62 ], basal cell carcinoma [ 63 ] and renal cell carcinoma [ 64 ]. In CRC, high GREM1 protein expression has been associated with low tumor stage and extended survival [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Gremlin-1 Promotes Colorectal Cancer Cell Metastasis by Activating ATF6 and Inhibiting ATF4 Pathways

Zhou

et al. 2022

Cells

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Cancer cell survival, function and fate strongly depend on endoplasmic reticulum (ER) proteostasis. Although previous studies have implicated the ER stress signaling network in all stages of cancer development, its role in cancer metastasis remains to be elucidated. In this study, we investigated the role of Gremlin-1 (GREM1), a secreted protein, in the invasion and metastasis of colorectal cancer (CRC) cells in vitro and in vivo. Firstly, public datasets showed a positive correlation between high expression of GREM1 and a poor prognosis for CRC. Secondly, GREM1 enhanced motility and invasion of CRC cells by epithelial–mesenchymal transition (EMT). Thirdly, GREM1 upregulated expression of activating transcription factor 6 (ATF6) and downregulated that of ATF4, and modulation of the two key players of the unfolded protein response (UPR) was possibly through activation of PI3K/AKT/mTOR and antagonization of BMP2 signaling pathways, respectively. Taken together, our results demonstrate that GREM1 is an invasion-promoting factor via regulation of ATF6 and ATF4 expression in CRC cells, suggesting GREM1 may be a potential pharmacological target for colorectal cancer treatment.

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“…One of the functionally relevant proteins, haptoglobin, was further selected for clinical verification using individual plasma samples. Haptoglobin is an acute phase protein which is mainly synthesized in liver and is reported to be overexpressed in various types of cancers including GBC and reported to promote cell proliferation, migration and invasion, which implies its role in pathophysiological process of GBC ( 31 – 33 ). Clinical verification of HP by quantitative ELISA in the present study showed significantly increased levels in GBC in comparison to controls (health volunteers and GSD cases) ( Figure 5A ).…”

Section: Discussionmentioning

confidence: 99%

Proteomic profiling of cell line-derived extracellular vesicles to identify candidate circulatory markers for detection of gallbladder cancer

et al. 2022

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Gallbladder cancer (GBC) is the sixth most common gastrointestinal tract cancer with a very low overall survival and poor prognosis. Profiling of cancer-derived extracellular vesicles (EVs) is an emerging strategy for identification of candidate biomarkers for the detection and prognosis of the disease. The aim of the study was to analyse the protein content from GBC cell line- derived EVs with emphasis on proteins which could be used as candidate biomarkers for the detection of GBC. NOZ and OCUG-1 cell lines were cultured and EVs were isolated from conditioned media. LC-MS/MS analysis of total EV proteins led to the identification of a total of 268 proteins in both the cell lines. Of these, 110 proteins were identified with ≥2 unique peptides with ≥2 PSMs in at least two experimental and technical replicate runs. STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) database was used to perform bioinformatics analysis of 110 proteins which showed ‘cell adhesion molecule binding’, ‘integrin binding’, ‘cadherin binding’ among the top molecular functions and ‘focal adhesion’ to be among the top pathways associated with the EV proteins. A total of 42 proteins including haptoglobin (HP), pyruvate kinase (PKM), annexin A2 (ANXA2), thrombospondin 1 (THBS1), were reported to be differentially abundant in GBC tissue. Of these, 16 proteins were reported to be differentially abundant in plasma and plasma-derived EVs. We infer these proteins to be highly important to be considered as potential circulatory biomarkers for the detection of GBC. To check the validity of this hypothesis, one of the proteins, haptoglobin (HP) as a representative case, was analysed in plasma by quantitative Enzyme- linked immunosorbent assay (ELISA) and we observed its increased levels in GBC in comparison to controls (p value= 0.0063). Receiver operating characteristic (ROC) curve analysis for GBC vs controls showed an Area under the ROC Curve (AUC) of 0.8264 for HP with 22% sensitivity against 100% specificity. We propose that HP along with other candidate proteins may be further explored for their clinical application.

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Prognostic and clinicopathological significance of Hapto and Gremlin1 expression in extrahepatic cholangiocarcinoma

Cited by 4 publications

References 42 publications

Prognostic models for mucinous and non-specific adeno cholangiocarcinoma: a population-based retrospective study

Prognostic models for mucinous and non-specific adeno cholangiocarcinoma: a population-based retrospective study

Gremlin-1 Promotes Colorectal Cancer Cell Metastasis by Activating ATF6 and Inhibiting ATF4 Pathways

Proteomic profiling of cell line-derived extracellular vesicles to identify candidate circulatory markers for detection of gallbladder cancer

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