Diagnostic accuracy of liquid biopsy in endometrial cancer

Background: Liquid biopsy is a minimally invasive collection of a patient body fluid sample. In oncology, they offer several advantages compared to traditional tissue biopsies. However, the potential of this method in endometrial cancer (EC) remains poorly explored. We studied the utility of tumor educated platelets (TEPs) and circulating tumor DNA (ctDNA) for preoperative EC diagnosis, including histology determination. Methods: TEPs from 295 subjects (53 EC patients, 38 patients with benign gynecologic conditions, and 204 healthy women) were RNA-sequenced. DNA sequencing data were obtained for 519 primary tumor tissues and 16 plasma samples. Artificial intelligence was applied to sample classification. Results: Platelet-dedicated classifier yielded AUC of 97.5% in the test set when discriminating between healthy subjects and cancer patients. However, the discrimination between endometrial cancer and benign gynecologic conditions was more challenging, with AUC of 84.1%. ctDNA-dedicated classifier discriminated primary tumor tissue samples with AUC of 96% and ctDNA blood samples with AUC of 69.8%. Conclusions: Liquid biopsies show potential in EC diagnosis. Both TEPs and ctDNA profiles coupled with artificial intelligence constitute a source of useful information. Further work involving more cases is warranted.publishedVersio

Detection and localization of early- and late-stage cancers using platelet RNA

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening

Vaginal hysterectomy as a method of treatment of endometrial cancer

The aim of this paper is to assess transvaginal hysterectomy as a technique of surgical treatment of selected group of patients (n=28) with endometrial cancer, treated at the Department of Gynecology and Oncological Gynecology of Medical University in Gdańsk since 1983 thru 2008. Material and methods: Analysis encompassed the following clinical parameters: patients’ age, number of deliveries, coexisting internal medical diseases, past surgical procedures, body weight and BMI index, histological grade and clinical stage of endometrial cancer, depth of myometrial infiltration and invasion of uterine cervix by the tumor, intra- and postoperative complications. Due to retrospective character of the study, FIGO 1988 classification of endometrial cancer based on surgical-pathomorphological criteria was used throughout the text. Results: The youngest patient was 42, the oldest – 82. Twenty seven women (96.4%) were at postmenopausal age and only one (3.6%) – at premenopausal age. Most patients have had 2 or 3 deliveries. In the study population, the lowest body weight was 72 kg, the highest – 230 kg. Obese and pathologically obese patients predominated, whereby 60.5% of the patients weighted over 100 kg. In this group, 26 patients (92.9%) had a serious internal medical comorbidity and only 2 patients (7.1%) did not report any coexisting disease. In the group of patients operated on by transvaginal approach, the predominating histological type was adenocarcinoma. Over one-half of the patients had low-stage cancer, limited to endometrium only or not exceeding one-half of myometrial layer. In this group, coexisting superficial invasion of uterine cervix was seen in 3 cases and coexisting cervical cancer in 1 case. Conclusion: Selected group of patients with endometrial cancer presented in this paper proves the feasibility of treating this type of malignancy by transvaginal route.Cel pracy: Celem pracy była próba oceny histerektomii przezpochwowej jako metody leczenia chirurgicznego w wyselekcjonowanej grupie 28 chorych na raka trzonu macicy operowanych metodą pochwową w Klinice Ginekologii i Ginekologii Onkologicznej Gdańskiego Uniwersytetu Medycznego w latach 1983-2008. Materiał i metody: Dokonano analizy następujących parametrów klinicznych: wieku chorych, liczby przebytych porodów, współistniejących schorzeń internistycznych, przebytych zabiegów chirurgicznych, wagi oraz współczynnika BMI, postaci histologicznej oraz stopnia klinicznego zaawansowania raka błony śluzowej trzonu macicy, głębokości nacieku mięśniówki macicy oraz zajęcia szyjki macicy przez proces nowotworowy, powikłań śród- i pooperacyjnych. Ze względu na retrospektywny charakter badań w pracy zastosowano chirurgiczno-patomorfologiczną klasyfikację stopnia klinicznego zaawansowania raka błony śluzowej trzonu macicy według FIGO z 1988 roku. Wyniki: Najmłodsza operowana pacjentka miała 42, najstarsza – 82 lata. Dwadzieścia siedem kobiet (96,4%) było w wieku pomenopauzalnym, a tylko 1 chora (3,6%) w wieku przedmenopauzalnym. Większość pacjentek rodziła 2 lub 3 razy. W analizowanej grupie kobiet najniższa waga wynosiła 72 kg, najwyższa – 230 kg. Przeważały pacjentki otyłe i z otyłością patologiczną: 60,5% chorych ważyło ponad 100 kg. W badanej grupie 92,9% (26 chorych) stanowiły kobiety z obciążonym wywiadem internistycznym, jedynie 2 pacjentki (7,1%) nie podały żadnych współistniejących chorób. W grupie chorych operowanych metodą pochwową najczęściej stwierdzanym typem histologicznym był gruczolakorak. U ponad połowy chorych operowanych metodą pochwową odnotowano niewielkie zaawansowanie raka trzonu macicy (zmiana obejmująca jedynie endometrium lub naciek nieprzekraczający połowy mięśniówki macicy). Jednocześnie stwierdzono 3 przypadki współistniejącego powierzchownego naciekania szyjki macicy oraz 1 przypadek współistniejącego raka szyjki macicy. Wnioski: Przedstawiona wyselekcjonowana grupa chorych na raka trzonu macicy stanowi przykład alternatywnego leczenia tego nowotworu drogą pochwową

Tumor Heterogeneity at Protein Level as an Independent Prognostic Factor in Endometrial Cancer

Intratumor heterogeneity implies heterogeneous protein function, facilitating tumor adaptation which results in therapeutic failure. We hypothesized that tumor heterogeneity at protein level may influence the course of the disease. As a single biopsy might not represent the full biologic complexity of the tumor, we have analyzed immunohistochemically four different cores obtained from each primary tumor within the cohort of 364 patients with endometrial cancer (EC). The following proteins were examined: estrogen receptor 1 (ESR1), progesterone receptor, epidermal growth factor receptor, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, receptor tyrosine-protein kinase erbB-3, v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4, phosphatidylinositol-4,5-bisphosphate 3-kinase, phosphorylated v-akt murine thymoma viral oncogene homolog 1, v-myc avian myelocytomatosis viral oncogene homolog, DNA topoisomerase II alpha 170 kDa (TOP2A), cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein p53, RAD21 homolog, S. pombe, and runt-related transcription factor 1. Particularly strong correlation was found between TOP2A and CDKN2A heterogeneity and higher stage of the disease (P = .0002 and P = .0003, respectively). Most correlations with clinicopathologic data were observed for ESR1 heterogeneity that correlated with non-endometrioid carcinomas (P=.02), higher stage (P=.005), grade (P=.01), and the presence of metastases (P = .01). Thirty-nine (11.0%) patients were classified as “globally heterogeneous”. Cumulative tumor heterogeneity strongly correlated with the presence of metastases, higher stage, and higher grade of the disease (all P b .05). It also carried negative prognostic value (P=.0008). We show that the degree of heterogeneity in EC might serve as a clinically valid molecular marker

imPlatelet classifier: image-converted RNA biomarker profiles enable blood-based cancer diagnostics

Liquid biopsies offer a minimally invasive sample collection, outperforming traditional biopsies employed for cancer evaluation. The widely used material is blood, which is the source of tumor-educated platelets. Here, we developed the imPlatelet classifier, which converts RNA-sequenced platelet data into images in which each pixel corresponds to the expression level of a certain gene. Biological knowledge from the Kyoto Encyclopedia of Genes and Genomes was also implemented to improve accuracy. Images obtained from samples can then be compared against standard images for specific cancers to determine a diagnosis. We tested imPlatelet on a cohort of 401 non-small cell lung cancer patients, 62 sarcoma patients, and 28 ovarian cancer patients. imPlatelet provided excellent discrimination between lung cancer cases and healthy controls, with accuracy equal to 1 in the independent dataset. When discriminating between noncancer cases and sarcoma or ovarian cancer patients, accuracy equaled 0.91 or 0.95, respectively, in the independent datasets. According to our knowledge, this is the first study implementing an image-based deep-learning approach combined with biological knowledge to classify human samples. The performance of imPlatelet considerably exceeds previously published methods and our own alternative attempts of sample discrimination. We show that the deep-learning image-based classifier accurately identifies cancer, even when a limited number of samples are available

Diagnostic accuracy of liquid biopsy in endometrial cancer

Background: Liquid biopsy is a minimally invasive collection of a patient body fluid sample. In oncology, they offer several advantages compared to traditional tissue biopsies. However, the potential of this method in endometrial cancer (EC) remains poorly explored. We studied the utility of tumor educated platelets (TEPs) and circulating tumor DNA (ctDNA) for preoperative EC diagnosis, including histology determination. Methods: TEPs from 295 subjects (53 EC patients, 38 patients with benign gynecologic conditions, and 204 healthy women) were RNA-sequenced. DNA sequencing data were obtained for 519 primary tumor tissues and 16 plasma samples. Artificial intelligence was applied to sample classification. Results: Platelet-dedicated classifier yielded AUC of 97.5% in the test set when discriminating between healthy subjects and cancer patients. However, the discrimination between endometrial cancer and benign gynecologic conditions was more challenging, with AUC of 84.1%. ctDNA-dedicated classifier discriminated primary tumor tissue samples with AUC of 96% and ctDNA blood samples with AUC of 69.8%. Conclusions: Liquid biopsies show potential in EC diagnosis. Both TEPs and ctDNA profiles coupled with artificial intelligence constitute a source of useful information. Further work involving more cases is warranted