Novel biomarker SARIFA in colorectal cancer: highly prognostic, not genetically driven and histologic indicator of a distinct tumor biology

SARIFA (Stroma AReactive Invasion Front Areas) has recently emerged as a promising histopathological biomarker for colon and gastric cancer. To elucidate the underlying tumor biology, we assessed SARIFA-status in tissue specimens from The-Cancer-Genome-Atlas (TCGA) cohorts COAD (colonic adenocarcinoma) and READ (rectal adenocarcinoma). For the final analysis, 207 CRC patients could be included, consisting of 69 SARIFA-positive and 138 SARIFA-negative cases. In this external validation cohort, H&E-based SARIFA-positivity was strongly correlated with unfavorable overall, disease-specific, and progression-free survival, partly outperforming conventional prognostic factors. SARIFA-positivity was not associated with known high-risk genetic profiles, such as BRAF V600E mutations or microsatellite-stable status. Transcriptionally, SARIFA-positive CRCs exhibited an overlap with CRC consensus molecular subtypes CMS1 and CMS4, along with distinct differential gene expression patterns, linked to lipid metabolism and increased stromal cell infiltration scores (SIIS). Gene-expression-based drug sensitivity prediction revealed a differential treatment response in SARIFA-positive CRCs. In conclusion, SARIFA represents the H&E-based counterpart of an aggressive tumor biology, demonstrating a partial overlap with CMS1/4 and also adding a further biological layer related to lipid metabolism. Our findings underscore SARIFA-status as an ideal biomarker for refined patient stratification and novel drug developments, particularly given its cost-effective assessment based on routinely available H&E slides

Clinical relevance of biomarkers in cholangiocarcinoma: critical revision and future directions

Cholangiocarcinoma (CCA) is a malignant tumour arising from the biliary system. In Europe, this tumour frequently presents as a sporadic cancer in patients without defined risk factors and is usually diagnosed at advanced stages with a consequent poor prognosis. Therefore, the identification of biomarkers represents an utmost need for patients with CCA. Numerous studies proposed a wide spectrum of biomarkers at tissue and molecular levels. With the present paper, a multidisciplinary group of experts within the European Network for the Study of Cholangiocarcinoma discusses the clinical role of tissue biomarkers and provides a selection based on their current relevance and potential applications in the framework of CCA. Recent advances are proposed by dividing biomarkers based on their potential role in diagnosis, prognosis and therapy response. Limitations of current biomarkers are also identified, together with specific promising areas (ie, artificial intelligence, patient-derived organoids, targeted therapy) where research should be focused to develop future biomarkers

Test time transform prediction for open set histopathological image recognition

Comunicació presentada a 25th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2022), celebrat del 18 al 22 de setembre de 2022 a Sentosa, Singapur.Tissue typology annotation in Whole Slide histological images is a complex and tedious, yet necessary task for the development of computational pathology models. We propose to address this problem by applying Open Set Recognition techniques to the task of jointly classifying tissue that belongs to a set of annotated classes, e.g. clinically relevant tissue categories, while rejecting in test time Open Set samples, i.e. images that belong to categories not present in the training set. To this end, we introduce a new approach for Open Set histopathological image recognition based on training a model to accurately identify image categories and simultaneously predict which data augmentation transform has been applied. In test time, we measure model confidence in predicting this transform, which we expect to be lower for images in the Open Set. We carry out comprehensive experiments in the context of colorectal cancer assessment from histological images, which provide evidence on the strengths of our approach to automatically identify samples from unknown categories. Code is released at https://github.com/agaldran/t3po.This work was partially supported by a Marie Sklodowska-Curie Global Fellowship (No. 892297) and by Australian Research Council grants (DP180103232 and FT190100525)

Serum levels of miR-29, miR-122, miR-155 and miR-192 are elevated in patients with cholangiocarcinoma

Objectives Cholangiocarcinoma (CCA) represents the second most common primary hepatic malignancy. Despite tremendous research activities, the prognosis for the majority of patients is still poor. Only in case of early diagnosis, liver resection might potentially lead to long-term survival. However, it is still unclear which patients benefit most from extensive liver surgery, highlighting the need for new diagnostic and prognostic stratification strategies. Methods Serum concentrations of a 4 miRNA panel (miR-122, miR-192, miR-29b and miR-155) were analyzed using semi-quantitative reverse-transcriptase PCR in serum samples from 94 patients with cholangiocarcinoma undergoing tumour resection and 40 healthy controls. Results were correlated with clinical data. Results Serum concentrations of miR-122, miR-192, miR-29b and miR-155 were significantly elevated in patients with CCA compared to healthy controls or patients with primary sclerosing cholangitis without malignant transformation. Although preoperative levels of these miRNAs were unsuitable as a prognostic marker of survival, a strong postoperative decline of miR-122 serum levels was significantly associated with a favorable patients' prognosis. Conclusions Analysis of circulating miRNAs represents a promising tool for the diagnosis of even early stage CCA. A postoperative decline in miRNA serum concentrations might be indicative for a favorable patients' outcome and helpful to identify patients with a good prognosis after extended liver surgery

High baseline soluble urokinase plasminogen activator receptor (suPAR) serum levels indicate adverse outcome after resection of pancreatic adenocarcinoma

Surgical resection represents the only potentially curative therapy for patients with pancreatic adenocarcinoma (PDAC), an aggressive malignancy with a very limited 5-year survival rate. However, even after complete tumor resection, many patients are still facing an unfavorable prognosis underlining the need for better preoperative stratification algorithms. Here, we explored the role of the secreted glycoprotein soluble urokinase plasminogen activator receptor (suPAR) as a novel circulating biomarker for patients undergoing resection of PDAC. Serum levels of suPAR were measured by enzyme-linked immunosorbent assay (ELISA) in an exploratory as well as a validation cohort comprising a total of 127 PDAC patients and 75 healthy controls. Correlating with a cytoplasmic immunohistochemical expression of uPAR in PDAC tumor cells, serum levels of suPAR were significantly elevated in PDAC patients compared to healthy controls and patient with PDAC precursor lesions. Importantly, patients with high preoperative suPAR levels above a calculated cutoff value of 5.956 ng/ml showed a significantly reduced overall survival after tumor resection. The prognostic role of suPAR was further corroborated by uni- and multivariate Cox-regression analyses including parameters of systemic inflammation, liver and kidney function as well as clinico-pathological patients' characteristics. Moreover, high baseline suPAR levels identified those patients particularly susceptible to acute kidney injury and surgical complications after surgery. In conclusion, our data suggest that circulating suPAR represents a novel prognostic marker in PDAC patients undergoing tumor resection that might be a useful addition to existing preoperative stratification algorithms for identifying patients that particularly benefit from extended tumor resection