The Strain Ratio as Obtained by Endoscopic Ultrasonography Elastography Correlates With the Stroma Proportion and the Prognosis of Local Pancreatic Cancer

Shi, Si; Liang, Chen; Xu, Jin; Meng, Qingcai; Hua, Jie; Yang, Xunan; Ni, Quanxing; Lei, Yu

doi:10.1097/sla.0000000000002998

Cited by 33 publications

(36 citation statements)

References 22 publications

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“…Tumor stroma is a key component of pancreatic cancer. An increase in stroma reduces the efficacy of chemotherapy drugs (21). The present study showed that the expression of CTHRC1, a stroma related protein, was higher in the hypodense group.…”

Section: Discussionsupporting

confidence: 51%

Hyperdense Pancreatic Ductal Adenocarcinoma: Clinical Characteristics and Proteomic Landscape

Hua

Meng

et al. 2021

Front. Oncol.

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PurposeHypodensity of pancreatic ductal adenocarcinoma (PDAC) during contrast-enhanced computed tomography (CECT) examination is common, but a minority of PDAC patients exhibit hyperdense images. The present study examined the clinical characteristics and protein landscape of PDAC with hyperdensity.Materials and MethodsA total of 844 pathologically confirmed PDAC patients who underwent CECT before surgery were included. During the parenchymal phase of CECT, patients were assigned to the hyperdense or hypodense group based on CT values. Clinical and CT characteristics for predicting relapse-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan–Meier method and Cox proportional hazards model. The expression of the tumor angiogenesis marker CD31 and stroma-related protein CTHRC1 were analyzed using immunohistochemistry (IHC) assay to evaluate differences between the two groups. Proteomics was performed to compare the possible mechanisms underlying the differential enhancement on CT scans.ResultsBased on CECT, 43 and 801 PDAC patients had hyperdense and hypodense lesions, respectively. All 43 patients presented a hyperdense lesion in the parenchymal phase. The mean CECT values of the hyperdense group were higher than the hypodense group (102.5 ± 17.4 and 53.7 ± 18.7, respectively, P< 0.001). The hyperdense group had a better prognosis than the hypodense group (median RFS, 19.97 vs. 12.34 months, P = 0.0176; median OS, 33.6 vs. 20.3 months, P = 0.047). Multivariate analysis showed that age, higher CA19-9 levels (> 300 U/ml), tumor stage, tumor differentiation, tumor CT density, and adjuvant chemotherapy were significant independent prognostic factors for OS. CD31 immunohistochemical staining showed that the hyperdense PDACs had a higher microvessel density than the hypodense group (P< 0.001). CTHRC1 expression was higher in the hypodense group (P = 0.019). Sixty-eight differentially expressed proteins were found using the tandem mass tag labeling-based quantification of the proteomes of PDAC tissue samples, and 7 proteins (POFUT1, PKP2, P0DOX4, ITPR1, HBG2, IGLC3, SAA2) were related to angiogenesis.ConclusionPatients who presented with a hyperdense mass on CECT had a higher microvessel density and better prognosis. Anti-angiogenic therapy may be suitable for these patients.

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Section: Discussionsupporting

confidence: 51%

Hyperdense Pancreatic Ductal Adenocarcinoma: Clinical Characteristics and Proteomic Landscape

Hua

Meng

et al. 2021

Front. Oncol.

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“…Probably tumors with high stromal component are characteristic by hardness, so the surgeons tended to resect more pancreatic tissue to achieve a negative margin. However, no consensus has been reached on the prognostic impact of stromal component in patients with PDAC based on previous studies (7)(8)(9). We also found that TSR categories could be a strong and independent prognostic factor in patients with PDAC and demonstrated that the prognostic impact of TSR was almost similar with tumor grade and perineural invasion, which are regularly included in pathological reports.…”

Section: Discussionmentioning

confidence: 55%

“…Nevertheless, there exist some discrepancies in the prognostic impact of TSR in patients with PDAC. Using Masson trichrome staining or α-smooth muscle actin (α-SMA) staining in surgical specimen sections to evaluate stromal proportion, Shi et al reported that a stromal proportion of ≤60% was of benefit for prognosis in PDAC (7). Heid et al demonstrated that low tumor cellularity with a cutoff value of 30%, which was equivalent to a high amount of stroma, indicated better prognosis (8).…”

Section: Introductionmentioning

confidence: 99%

Pros and Cons: High Proportion of Stromal Component Indicates Better Prognosis in Patients With Pancreatic Ductal Adenocarcinoma—A Research Based on the Evaluation of Whole-Mount Histological Slides

Wang

Jiang

et al. 2020

Front. Oncol.

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The study aimed to investigate the potential of tumor–stroma ratio (TSR) on digitalized whole-mount histopathology to predict prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). The effectiveness were evaluated through internal validation. Data were retrospectively collected from consecutive patients who underwent primary pancreatic resection from December 2016 to August 2017 (developing cohort) and from September 2017 to April 2018 (validation cohort). Digitalized whole-mount slide images were used to evaluate TSR by both pathologists and a computerized model based on Conditional Generative Adversarial Model (cGAN), respectively. TSR>1 and ≤ 1 denoted low and high stromal component. Logistic regression analysis revealed intratumoral necrosis and R1 independently associated with low stromal component in the developing cohort. Cox regression analysis revealed tumor–node–metastasis (TNM) stage [II vs. I: hazard ratio (HR), 2.584; 95% CI, 1.386–4.819; P = 0.003; III vs. I: HR, 4.384; 95% CI, 2.285–8.411; P < 0.001], stromal component (low vs. high: HR, 1.876; 95% CI, 1.227–2.870; P = 0.004), tumor grade (G3 vs. G1/2: HR, 2.124; 95% CI, 1.419–3.179; P < 0.001), and perineural invasion (with vs. without: HR, 2.147; 95% CI, 1.187–3.883; P = 0.011) were independent prognostic factors in the developing cohort. Stromal component categories could classify patients into subgroups within TNM stages I, II, and III based on over survival. All results were validated in the validation cohort. The weighted kappa value for categorical assessments between pathologists' evaluation and computer-aided evaluation was 0.804 (95% CI, 0.573–0.951). TSR represents a simple and reliable metric for combining the prognostic value of TNM stage in patients with PDAC.

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“…The TME, the 'soil' of tumor growth, is composed of cancer cells and various interstitial cells, including the extracellular matrix, proteolytic enzymes, cytokines and chemokines, and interacts with tumors by altering the proteome and degradome (8)(9)(10). As a prominent member of the stroma and as the most stromal or interstitial cells in the TME, CAFs have their own gene expression profiles that are different from NFs, and interact with cancer cells via a variety of signals to affect the TME, tumorigenesis, development and therapeutic tolerance of cancer cells (11)(12)(13), which are also associated with the prognosis of various tumors by expressing FAP, FGF-2, IL-1β-IRAK4 and Podoplanin (15,16,(40)(41)(42)(43)(44). Notably, the presence of reactive stroma in the TME, particularly in CAFs, was revealed to affect the tumor treatment effectiveness and was associated with tumor drug resistance (17)(18)(19)(20).…”

Section: Univariate Analysis Multivariate Analysis ------------------mentioning

confidence: 99%

“…Recent studies have demonstrated the critical role of CAFs in cancer stroma for tumorigenesis, development and the targeted therapy of cancers (8)(9)(10). In addition, tumor treatment effectiveness is complicated by the presence of reactive stroma in the Upregulated NOX1 expression in gallbladder cancer-associated fibroblasts predicts a poor prognosis TME, which is associated with tumor invasiveness and drug resistance (10)(11)(12)(13). CAFs have their own gene expression profiles that are different from normal fibroblasts (NFs), and they interact with cancer cells via a variety of signals in a paracrine or autocrine manner to affect the TME, determine cancer cell growth, invasion, metastasis, angiogenesis and therapeutic tolerance (14)(15)(16)(17), and predict the poor prognosis of patients (18,19).…”

Section: Introductionmentioning

confidence: 99%

Upregulated NOX1 expression in gallbladder cancer‑associated fibroblasts predicts a poor prognosis

et al. 2019

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Gallbladder cancer (GBC) is a lethal aggressive malignant neoplasm of the biliary tract. Potential prognostic markers and therapeutic targets for this disease are urgently required. Cancer-associated fibroblasts (CAFs) play a key role in tumorigenesis and the development of cancer. Nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1) expression has been reported to be involved in tumorigenesis and useful for tumor prognosis. However, NOX1 expression in the stroma of GBCs, particularly gallbladder cancer-associated fibroblasts (GCAFs), and its prognostic significance in GBC patients remains unclear. In the present study, NOX1 expression in the stroma of human gallbladder lesions in vivo was investigated, as well as in GCAFs and co-cultures of GBC-SD+GCAFs in vitro, and their correlation with clinicopathological parameters and the prognosis of GBC patients were evaluated. The results revealed that NOX1 expression was significantly upregulated in the stroma of GBCs compared with precancerous and benign lesions of the gallbladder; NOX1 expression was localized to gallbladder stromal fibroblasts expressing α-smooth muscle actin and fibroblast secreted protein-1. Furthermore, these observations were confirmed by the fact that NOX1 expression was upregulated in GCAFs as determined by Affymetrix gene profile chip analysis and reverse transcription-quantitative PCR. In addition, overexpression was observed in formed spheroids of GBC-SD+GCAF co-cultures by immunohistochemistry and western blotting in vitro. Thus, it was verified that NOX1 expression was upregulated in GCAFs. Furthermore, upregulated stromal NOX1 expression was correlated with aggressive characteristics such as differentiation degree (P=0.042), venous invasion (P=0.041), resection methods (P=0.002), and a lower survival rate (P=0.025, log-rank test) of patients with GBC. Stromal NOX1 expression (P=0.047) was an independent prognostic factor for the overall survival rate of patients with GBC. GBC patients with upregulated NOX1 expression in GCAFs had a poorer prognosis. These results revealed that stromal NOX1 may be a novel biomarker and/or target, and may contribute to the discovery of new tumor markers and potential targeted therapeutics for human GBCs.

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The Strain Ratio as Obtained by Endoscopic Ultrasonography Elastography Correlates With the Stroma Proportion and the Prognosis of Local Pancreatic Cancer

Abstract: A high SR as obtained by endoscopic ultrasonography elastography was associated with poor prognosis of resected pancreatic cancer but predicted improved survival for LAPC patients treated with the nab-paclitaxel and gemcitabine regimen.

Cited by 33 publications

References 22 publications

Hyperdense Pancreatic Ductal Adenocarcinoma: Clinical Characteristics and Proteomic Landscape

Hyperdense Pancreatic Ductal Adenocarcinoma: Clinical Characteristics and Proteomic Landscape

Pros and Cons: High Proportion of Stromal Component Indicates Better Prognosis in Patients With Pancreatic Ductal Adenocarcinoma—A Research Based on the Evaluation of Whole-Mount Histological Slides

Upregulated NOX1 expression in gallbladder cancer‑associated fibroblasts predicts a poor prognosis

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