Increased expression of calponin 2 is a positive prognostic factor in pancreatic ductal adenocarcinoma

Qiu, Zhaoyan; Chu, Yi; Xu, Bing; Wang, Qian; Jiang, Mingzuo; Li, Xiaowei; Wang, Gang; Yu, Pengfei; Liu, Guoxiao; Wang, Hua; Kang, Huijie; Liu, Jiayu; Jin, Jian‐Ping; Wu, Kaichun; Liang, Jie

doi:10.18632/oncotarget.17701

Cited by 8 publications

(9 citation statements)

References 38 publications

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“…Calponin-2 is an actin cytoskeleton-associated regulatory protein that can inhibit cell proliferation and migration. Calponin-2 has not been extensively studied in cancer, however, it was found to be a prognostic factor and to have tumor-suppressive effects in pancreatic and prostate cancers [ 73 , 74 ]. Collagen triple helix repeat-containing protein 1 is involved in the regulation of cell motility through the regulation of collagen deposition.…”

Section: Discussionmentioning

confidence: 99%

Mass spectrometry-based analysis of formalin-fixed, paraffin-embedded distal cholangiocarcinoma identifies stromal thrombospondin-2 as a potential prognostic marker

Byrling

Kristl

et al. 2020

J Transl Med

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Background: Distal cholangiocarcinoma is an aggressive malignancy with a dismal prognosis. Diagnostic and prognostic biomarkers for distal cholangiocarcinoma are lacking. The aim of the present study was to identify differentially expressed proteins between distal cholangiocarcinoma and normal bile duct samples. Methods: A workflow utilizing discovery mass spectrometry and verification by parallel reaction monitoring was used to analyze surgically resected formalin-fixed, paraffin-embedded samples from distal cholangiocarcinoma patients and normal bile duct samples. Bioinformatic analysis was used for functional annotation and pathway analysis. Immunohistochemistry was performed to validate the expression of thrombospondin-2 and investigate its association with survival. Results: In the discovery study, a total of 3057 proteins were identified. Eighty-seven proteins were found to be differentially expressed (q < 0.05 and fold change ≥ 2 or ≤ 0.5); 31 proteins were upregulated and 56 were downregulated in the distal cholangiocarcinoma samples compared to controls. Bioinformatic analysis revealed an abundance of differentially expressed proteins associated with the tumor reactive stroma. Parallel reaction monitoring verified 28 proteins as upregulated and 18 as downregulated in distal cholangiocarcinoma samples compared to controls. Immunohistochemical validation revealed thrombospondin-2 to be upregulated in distal cholangiocarcinoma epithelial and stromal compartments. In paired lymph node metastases samples, thrombospondin-2 expression was significantly lower; however, stromal thrombospondin-2 expression was still frequent (72%). Stromal thrombospondin-2 was an independent predictor of poor disease-free survival (HR 3.95, 95% CI 1.09-14.3; P = 0.037). Conclusion: Several proteins without prior association with distal cholangiocarcinoma biology were identified and verified as differentially expressed between distal cholangiocarcinoma and normal bile duct samples. These proteins can be further evaluated to elucidate their biomarker potential and role in distal cholangiocarcinoma carcinogenesis. Stromal thrombospondin-2 is a potential prognostic marker in distal cholangiocarcinoma.

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Section: Discussionmentioning

confidence: 99%

Mass spectrometry-based analysis of formalin-fixed, paraffin-embedded distal cholangiocarcinoma identifies stromal thrombospondin-2 as a potential prognostic marker

Byrling

Kristl

et al. 2020

J Transl Med

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“…In several human cancer types, calponin expression in tumor cells has been revealed as a positive prognostic marker [25,26,34,35]. The comparison of primary and metastatic adenocarcinomas revealed a 17-gene signature associated with metastases that included downregulated expression of calponin 1 [34].…”

Section: Discussionmentioning

confidence: 99%

“…The comparison of primary and metastatic adenocarcinomas revealed a 17-gene signature associated with metastases that included downregulated expression of calponin 1 [34]. In pancreatic ductal adenocarcinoma, a higher level of calponin 2 expression was associated with reduced lymph node metastasis and prolonged postsurgical survival time [35].…”

Section: Discussionmentioning

confidence: 99%

Expression of Myoepithelial Markers in Mammary Carcinomas of 119 Pet Rabbits

Degner

Schoon

Degner³

et al. 2019

Animals

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Simple SummaryMammary cancer is a serious health issue in pet rabbits; prognostic factors are unknown. In a normal mammary gland, glandular secretory cells are surrounded by a single continuous layer of myoepithelial cells. In non-invasive mammary carcinomas, tumor cells are delineated by an intact myoepithelial layer, which is gradually lost to invasive carcinomas. The main aim of this study was to determine in rabbit mammary carcinomas (n = 119) the expression of myoepithelial markers that have prognostic significance in human cancer. Results show that all cases contained some retained myoepithelial cells. In 93% of the tumors, neoplastic cells expressed the myoepithelial marker calponin. There was a statistically significant association between higher percentages of calponin-containing cancer cells and histological features indicative of a better tumor differentiation, i.e., a lower proliferation of tumor cells, an increased percentage of tubular growth within the tumor, and a lower tumor grade, respectively. These results suggest that rabbit mammary carcinomas develop from progression of non-invasive cancer forms, and that calponin expression in cancer cells likely represents a favorable prognostic factor. The latter hypothesis has to be confirmed in long-term follow-up studies.AbstractMost mammary tumors in pet rabbits are carcinomas; prognostic factors are unknown. The aim of this study on rabbit mammary carcinomas was to determine the expression of myoepithelial markers that have a prognostic relevance in human cancers. Mammary carcinomas (n = 119) of female or female-spayed pet rabbits were immunostained for cytokeratin AE1/AE3, vimentin, smooth muscle actin (SMA), and calponin; and percentages of non-neoplastic myoepithelial cells (ME cells) and calponin-positive neoplastic cells were determined. Using statistical analysis, data were correlated with the age of the rabbits and histological tumor characteristics. All carcinomas contained retained spindle-shaped ME, while 115 also contained hypertrophic ME (HME). A statistically significant relationship existed between a higher age and an increase in HME. In 111 carcinomas (93%), tumor cells expressed calponin. There was a significant correlation between higher percentages of calponin-positive tumor cells and a lower mitotic count, an increased percentage of tubular growth, and a lower grading score, respectively. Data suggest that pet rabbit mammary carcinomas develop from progression of in situ cancer and that the extent of calponin expression in tumor cells influences their biological behavior. These results provide the basis for a long-term follow-up on the prognostic significance of calponin expression in mammary cancer cells.

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“…Calponin is an actin cytoskeleton-binding protein that stabilizes actin filaments. Calponin has three forms, of which calponin 1 (CNN1) plays a vital role in regulating contractility [62]. CNN1, which is generally expressed in smooth muscle cells, can bind to thin filaments of actin, calmodulin, and tropomyosin.…”

Section: Proteins That Are Differentially Expressed In Hy Compared To...mentioning

confidence: 99%

Tissue-Based Proteomic Profiling in Patients with Hyperplasia and Endometrial Cancer

Akkour

Alanazi

Alfadda

et al. 2022

Cells

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Uterine cancers are among the most prevalent gynecological malignancies, and endometrial cancer (EC) is the most common in this group. This study used tissue-based proteomic profiling analysis in patients with endometrial cancer and hyperplasia, and control patients. Conventional 2D gel electrophoresis, followed by a mass spectrometry approach with bioinformatics, including a network pathway analysis pipeline, was used to identify differentially expressed proteins and associated metabolic pathways between the study groups. Thirty-six patients (twelve with endometrial cancer, twelve with hyperplasia, and twelve controls) were enrolled in this study. The mean age of the participants was 46–75 years. Eighty-seven proteins were significantly differentially expressed between the study groups, of which fifty-three were significantly differentially regulated (twenty-eight upregulated and twenty-five downregulated) in the tissue samples of EC patients compared to the control (Ctrl). Furthermore, 26 proteins were significantly dysregulated (8 upregulated and 18 downregulated) in tissue samples of hyperplasia (HY) patients compared to Ctrl. Thirty-two proteins (nineteen upregulated and thirteen downregulated) including desmin, peptidyl prolyl cis-trans isomerase A, and zinc finger protein 844 were downregulated in the EC group compared to the HY group. Additionally, fructose bisphosphate aldolase A, alpha enolase, and keratin type 1 cytoskeletal 10 were upregulated in the EC group compared to those in the HY group. The proteins identified in this study were known to regulate cellular processes (36%), followed by biological regulation (16%). Ingenuity pathway analysis found that proteins that are differentially expressed between EC and HY are linked to AKT, ACTA2, and other signaling pathways. The panels of protein markers identified in this study could be used as potential biomarkers for distinguishing between EC and HY and early diagnosis and progression of EC from hyperplasia and normal patients.

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Increased expression of calponin 2 is a positive prognostic factor in pancreatic ductal adenocarcinoma

Cited by 8 publications

References 38 publications

Mass spectrometry-based analysis of formalin-fixed, paraffin-embedded distal cholangiocarcinoma identifies stromal thrombospondin-2 as a potential prognostic marker

Mass spectrometry-based analysis of formalin-fixed, paraffin-embedded distal cholangiocarcinoma identifies stromal thrombospondin-2 as a potential prognostic marker

Expression of Myoepithelial Markers in Mammary Carcinomas of 119 Pet Rabbits

Tissue-Based Proteomic Profiling in Patients with Hyperplasia and Endometrial Cancer

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