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Preoperative heat shock protein 47 levels identify colorectal cancer patients with lymph node metastasis and poor prognosis.

ABSTRACT: Accumulating evidence suggests that overexpression of heat shock protein 47 (HSP47) increases cancer progression, and that HSP47 level in the tumor-associated stroma may serve as a diagnostic marker in various cancers. The present study aimed to evaluate whether HSP47 gene expression in colorectal cancer (CRC) tissues could be used to identify lymph node (LN) metastasis status preoperatively in patients with CRC. To do so, HSP47 gene expression was determined and its association with the clinicopathological characteristics of patients with CRC was analyzed. A total of 139 surgical specimens from patients with CRC and 36 patients with benign colonic disease undergoing surgery at Mie University Hospital were analyzed. HSP47 gene expression was determined by reverse transcription quantitative PCR using Power SYBR Green PCR methods. Expression level of HSP47 was significantly higher in CRC tissues compared with normal tissue from patients with benign colonic disease. Furthermore, high HSP47 expression was significantly associated with tumor progression, including high T stage, lymph node metastasis and venous invasion, and high TNM stage. High HSP47 expression may therefore serve as a novel predictive biomarker for determining patients with CRC and LN metastasis. According to Kaplan-Meier analysis, patients with high HSP47 expression level had significantly poorer overall survival than those with low HSP47 expression level. Furthermore, multivariate analyses identified HSP47 expression as an independent predictive marker for LN metastasis and poor overall survival in patients with CRC. In summary, the present study demonstrated that HSP47 expression may be considered as a novel biomarker for predicting LN metastasis status and prognosis in patients with CRC.

SUBMITTER: Mori K

PROVIDER: S-EPMC7583735 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Preoperative heat shock protein 47 levels identify colorectal cancer patients with lymph node metastasis and poor prognosis.

Mori Koichiro K Toiyama Yuji Y Okugawa Yoshinaga Y Ichikawa Takashi T Nagano Yuka Y Oki Satoshi S Shimura Tadanobu T Fujikawa Hiroyuki H Hiro Junichiro J Kobayash Minako M Araki Toshimitsu T Inoue Yasuhiro Y Mohri Yasuhiko Y Kusunoki Masato M

Oncology letters 20201007 6

Accumulating evidence suggests that overexpression of heat shock protein 47 (HSP47) increases cancer progression, and that HSP47 level in the tumor-associated stroma may serve as a diagnostic marker in various cancers. The present study aimed to evaluate whether HSP47 gene expression in colorectal cancer (CRC) tissues could be used to identify lymph node (LN) metastasis status preoperatively in patients with CRC. To do so, HSP47 gene expression was determined and its association with the clinico ...[more]

PMID: 33123244

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Project description:Lymph node involvement increases the risk of breast cancer recurrence. An accurate non-invasive assessment of nodal involvement is valuable in cancer staging, surgical risk, and cost savings. Radiomics has been proposed to pre-operatively predict sentinel lymph node (SLN) status; however, radiomic models are known to be sensitive to acquisition parameters. The purpose of this study was to develop a prediction model for preoperative prediction of SLN metastasis using deep learning-based (DLB) features and compare its predictive performance to state-of-the-art radiomics. Specifically, this study aimed to compare the generalizability of radiomics vs DLB features in an independent test set with dissimilar resolution. Dynamic contrast-enhancement images from 198 patients (67 positive SLNs) were used in this study. Of these subjects, 163 had an in-plane resolution of 0.7 × 0.7 mm2, which were randomly divided into a training set (approximately 67%) and a validation set (approximately 33%). The remaining 35 subjects with a different in-plane resolution (0.78 × 0.78 mm2) were treated as independent testing set for generalizability. Two methods were employed: (1) conventional radiomics (CR), and (2) DLB features which replaced hand-curated features with pre-trained VGG-16 features. The threshold determined using the training set was applied to the independent validation and testing dataset. Same feature reduction, feature selection, model creation procedures were used for both approaches. In the validation set (same resolution as training), the DLB model outperformed the CR model (accuracy 83% vs 80%). Furthermore, in the independent testing set of the dissimilar resolution, the DLB model performed markedly better than the CR model (accuracy 77% vs 71%). The predictive performance of the DLB model outperformed the CR model for this task. More interestingly, these improvements were seen particularly in the independent testing set of dissimilar resolution. This could indicate that DLB features can ultimately result in a more generalizable model.

Project description:BackgroundPelvic lymph node metastasis (LNM) is a crucial independent prognostic factor in cervical cancer (CCa) and serves as an indicator for radiation therapy as the primary or an adjuvant treatment option. However, preoperative diagnosis of LNM remains challenging. Thus, we aimed to identify biomarkers of LNM in patients with presumed early-stage CCa.MethodsThe differentially expressed genes (DEGs) between tumours with different lymph node statuses were identified by using The Cancer Genome Atlas database. Then, univariate Cox regression analysis and Kaplan-Meier analyses were utilized to screen overall survival (OS)-associated genes. Multivariate Cox analysis and logistical analysis were utilized to evaluate independent risk factors for OS and LNM, respectively. Subsequently, the protein level of fatty acid binding protein 4 (FABP4) was detected in normal cervical and CCa tissues by immunohistochemistry assays. EdU assays were performed to determine whether FABP4 altered the proliferation of cervical cancer cells. Wound healing and Transwell assays were conducted to explore the effects of FABP4 depletion on migratory and invasive abilities of cervical cancer cells. F-actin fluorescence staining were performed to investigate morphological change and Western blotting analyses were performed to determine epithelial mesenchymal transition-related marker expression and downstream signalling pathways.ResultsA total of 243 DEGs, including 55 upregulated and 188 downregulated DEGs, were found in CCa patients with LNM versus those without LNM. Among these, FABP4 was found to be closely associated with poor OS. Multivariate analysis uncovered that FABP4 was an independent risk factor for OS and LNM in patients with CCa. The immunohistochemical results verified dramatically increased FABP4 expression in CCa tissues compared to normal cervical epithelia and its association with poor OS and LNM. In vitro, The proliferation, migration and invasion of cervical cancer cells were significantly inhibited after knocking down of FABP4, which was accompanied by elevated expression of E-cadherin and downregulated expression of N-cadherin, Vimentin and p-AKT.ConclusionsFABP4 might be a promising biomarker of LNM and survival in patients with early-stage CCa and therefore could significantly contribute to the development of personalized prognosis prediction and therapy optimization.

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Preoperative heat shock protein 47 levels identify colorectal cancer patients with lymph node metastasis and poor prognosis.

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Preoperative heat shock protein 47 levels identify colorectal cancer patients with lymph node metastasis and poor prognosis.

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