Deep Learning Radiomics Model of Dynamic Contrast-Enhanced MRI for Evaluating Vessels Encapsulating Tumor Clusters and Prognosis in Hepatocellular Carcinoma.

BACKGROUND: Vessels encapsulating tumor cluster (VETC) is a critical prognostic factor and therapeutic predictor of hepatocellular carcinoma (HCC). However, noninvasive evaluation of VETC remains challenging. PURPOSE: To develop and validate a deep learning radiomic (DLR) model of dynamic contrast-enhanced MRI (DCE-MRI) for the preoperative discrimination of VETC and prognosis of HCC. STUDY TYPE: Retrospective. POPULATION: A total of 221 patients with histologically confirmed HCC and stratified this cohort into training set (n = 154) and time-independent validation set (n = 67). FIELD STRENGTH/SEQUENCE: A 1.5 T and 3.0 T; DCE imaging with T1-weighted three-dimensional fast spoiled gradient echo. ASSESSMENT: Histological specimens were used to evaluate VETC status. VETC+ cases had a visible pattern (≥5% tumor area), while cases without any pattern were VETC-. The regions of intratumor and peritumor were segmented manually in the arterial, portal-venous and delayed phase (AP, PP, and DP, respectively) of DCE-MRI and reproducibility of segmentation was evaluated. Deep neural network and machine learning (ML) classifiers (logistic regression, decision tree, random forest, SVM, KNN, and Bayes) were used to develop nine DLR, 54 ML and clinical-radiological (CR) models based on AP, PP, and DP of DCE-MRI for evaluating VETC status and association with recurrence. STATISTICAL TESTS: The Fleiss kappa, intraclass correlation coefficient, receiver operating characteristic curve, area under the curve (AUC), Delong test and Kaplan-Meier survival analysis. P value <0.05 was considered as statistical significance. RESULTS: Pathological VETC+ were confirmed in 68 patients (training set: 46, validation set: 22). In the validation set, DLR model based on peritumor PP (peri-PP) phase had the best performance (AUC: 0.844) in comparison to CR (AUC: 0.591) and ML (AUC: 0.672) models. Significant differences in recurrence rates between peri-PP DLR model-predicted VETC+ and VETC- status were found. DATA CONCLUSIONS: The DLR model provides a noninvasive method to discriminate VETC status and prognosis of HCC patients preoperatively. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

The effectiveness of hysteroscopy for the treatment of cesarean scar pregnancy: a retrospective cohort study.

BACKGROUND: Cesarean scar pregnancy (CSP) is a long-term complication of cesarean section characterized by the localization of a subsequent gestational sac within the scar area or niche developed as a result of a previous cesarean section. Its incidence has increased substantially because of the high global cesarean section rate in recent decades. Several surgical and drug treatments exist for this condition; however, there is currently no optimal treatment. This study compared the effectiveness of direct hysteroscopic removal of the gestational tissue and hysteroscopy combined with vacuum suction for the treatment of CSP. METHODS: From 2017 to 2023, 521 patients were diagnosed with CSP at our hospital. Of these patients, 45 underwent hysteroscopy. Among them, 28 underwent direct hysteroscopic removal (hysteroscopic removal group) and 17 underwent hysteroscopy combined with vacuum suction (hysteroscopic suction group). The clinical characteristics and outcomes of the hysteroscopic removal group and hysteroscopic suction group were analyzed. RESULTS: Among the 45 patients, the amount of bleeding and hospitalization cost were significantly higher in the hysteroscopic removal group than in the hysteroscopic suction group (33.8 mL vs. 9.9 mL, P < 0.001; and 8744.0 yuan vs. 5473.8 yuan, P < 0.001; respectively). The operation time and duration of hospitalization were significantly longer in the hysteroscopic removal group than in the hysteroscopic suction group (61.4 min vs. 28.2 min, P < 0.001; and 3.8 days vs. 2.4 days, P = 0.026; respectively). Three patients in the hysteroscopic removal group had uterine perforation and received laparoscopic repair during operation. No complications occurred in the hysteroscopic suction group. One patient in the hysteroscopic removal group received ultrasound-guided suction curettage due to postoperative moderate vaginal bleeding, and one patient in the hysteroscopic suction group received ultrasound-guided suction curettage due to postoperative gestational residue and elevated serum beta-human chorionic gonadotropin levels. Reproductive function was preserved in all patients. CONCLUSIONS: Hysteroscopy is an effective method for treating CSP. Compared with direct hysteroscopic removal, hysteroscopy combined with vacuum suction is more suitable for CSP. However, multicenter prospective studies with large sample sizes are required for verification of these findings.

Desmoid-type fibromatosis of the mesentery: a clinicopatho-logical and genetic analysis of 9 cases. / è‚ ç³»è†œéŸ§å¸¦æ ·çº¤ç»´ç˜¤ç— æ‚£è€ ä¸´åºŠç— ç†å­¦åˆ†æž.

Nine cases of mesenteric desmoid-type fibromatosis were diagnosed and treated in Taizhou Hospital, Wenzhou Medical University between January 2010 and May 2022, including 2 females and 7 males, aged 16 to 59 years. The lesions were in the mesentery of small intestine with 7 cases, ileocecal junction with 1 cases and transverse colon with 1 case. The tumors had an unclear boundary and no envelope, the section was solid, gray and tough. The mean maximum diameter was (10.7±8.5) cm (range 3.5-33.0 cm). Microscopically, fusiform fibroblasts and myofibroblasts were parallel, bunched or staggered, buried in a large amount of extracellular collagen. The cell morphology was relatively consistent, without obvious atypia, and mitosis was rare. Immunohistochemistry showed that the tumor cells were positive for vimentin (9/9), ß-catenin (9/9), while smooth muscle actin (5/9) stains were focally positive. Ki-67 proliferation index was 1%-10%. Cytokeratin Pan, S-100, STAT6, CD117, DOG1, CD34, desmin and anaplastic lymphoma kinase stains were negative. Genetic analysis showed that there were 7 cases of c.121G>A(p.Thr41Ala) mutation of CTNNB1 gene, 1 case of c.121G>A(p.Thr41Ala) and 1 case of c.134C>T(p.Ser45Phe) double mutation, and 1 case of wild type. Tumors were surgically resected in all 9 cases. Eight cases had no recurrence or metastasis, 1 case had recurrence 6 months later, and no recurrence or metastasis after additional surgical resection.

The Significance of INHBE Expression in the Cancer Cells of Clear-Cell Renal Cell Carcinoma.

BACKGROUND: Activins and inhibins are structurally related dimeric glycoprotein hormones belonging to the transforming growth factor-ß superfamily but whether they are also involved in malignancy is far from clear. No study has reported the expression of INHBE in kidney cancer. The purpose of this study was to examine the expressions of INHBE in the tumor tissue of patients with clear-cell renal cell carcinoma (ccRCC) and to explore the pathologic significance. METHODS: The INHBE mRNA expression in the tumor tissue of ccRCC patients was analyzed by using RNA sequencing data from the TCGA database. To examine the expression of inhibin ßE protein, 241 ccRCC patients were recruited and immunohistochemistry was performed on the tumor tissue of these patients along with 39 normal renal samples. The association between the inhibin ßE expression level and patient's clinicopathological indices was evaluated. RESULTS: In the normal renal tissue, inhibin ßE was found to be expressed mainly by renal tubular epithelial cells. In the tumor tissue, inhibin ßE was expressed mainly in cancer cells. The expressions of INHBE mRNA and protein in the tumor tissue of ccRCC patients increased significantly compared with those in normal renal samples. There was a significant correlation between the level of inhibin ßE in the tumor tissue and tumor grade. Patients with a lower inhibin ßE expression in the tumor tissue were found to have a longer overall survival and disease-specific survival. CONCLUSIONS: INHBE might be involved in the pathogenesis of ccRCC and function as a tumor promoter.

Methyl CpG binding protein 2 promotes colorectal cancer metastasis by regulating N6 -methyladenosine methylation through methyltransferase-like 14.

RNA N6 -methyladenosine (m6 A) is an emerging regulatory mechanism for tumor progression in several types of cancer. However, the underlying regulation mechanisms of m6 A methylation in colorectal cancer (CRC) remain unknown. Although the oncogenic function of methyl CpG binding protein 2 (MeCP2) has been reported, it is still unclear whether MeCP2 could alter RNA m6 A methylation state. Here, we systematically identified MeCP2 as a prometastasis gene to regulate m6 A methylation in CRC. Interestingly, MeCP2 could bind to methyltransferase-like 14 (METTL14) to coregulate tumor suppressor Kruppel-like factor 4 (KLF4) expression through changing m6 A methylation modification. Furthermore, insulin-like growth factor 2 mRNA-binding protein 2 recognized the unique modified m6 A methylation sites to enhance KLF4 mRNA stability. Taken together, these findings highlight the novel function of MeCP2 for regulating m6 A methylation and reveal the underlying molecular mechanism for the interaction between MeCP2 and METTL14, which offers a better understanding of CRC progression and metastasis.

Association of TET1 expression with colorectal cancer progression.

OBJECTIVE: The ten-eleven translocation (TET) proteins, as methylcytosine dioxygenases, catalyze 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). The altered expression of TET1 disrupts the balance between DNA methylation and demethylation. This alteration has been reported to be associated with carcinogenesis in various malignancies. The aim of the present study was to investigate changes in expression and the role of TET1 in colorectal cancer (CRC). MATERIAL AND METHODS: A total of 109 CRC patients who underwent radical surgical colon resection were enrolled. The QuantiGene Plex Assay was used to detect the expression of TET1 in CRC tissues and matching adjacent normal tissues. We analyzed the associations between TET1 expression levels and various clinicopathologic features of CRC. TET1 overexpression and depletion cells were constructed to investigate its biological role in CRC. RESULTS: Compared to normal tissues, the expression level of TET1 in CRC was significantly lower. The ratio of TET1 in CRC tissues to that in adjacent normal tissues (C/N-TET1) was an independent overall survival predictive factor. Moreover, in vitro studies showed that TET1 could inhibit cell growth and promote cell metastasis and invasion. CONCLUSIONS: These findings indicated that TET1 played a multifaceted role in the pathogenesis of CRC, and thereby resulting in multiple effects on tumor progression.

[Neuroendocrine differentiation and Wilms' tumor protein-1 expression in breast mucinous carcinoma and their significance].

OBJECTIVE: To investigate neuroendocrine differentiation and Wilms' tumor protein-1 (WT-1) expression in breast mucinous carcinoma and their clinicopathological significance. METHODS: The clinicopathological data of 65 patients with breast mucinous carcinoma, including 31 cases of mixed mucinous carcinoma, 23 cases of hypocellular pure mucinous carcinoma and 11 cases of hypercellular pure mucinous carcinoma, admitted in Taizhou Hospital from January 2010 to June 2015 were retrospectively reviewed. The expression of neuroendocrine markers and WT-1 was detected by immunohistochemistry staining in all cases. RESULTS: The mixed mucinous carcinomas and hypercelluar pure mucinous carcinomas had higher incidence of axillary lymph node metastasis and human epidermal recepter 2 (HER-2) positive than hypocellular pure mucinous carcinoma (all (P<0.01). However, the difference was not significant between mixed mucinous carcinomas and hypercellular pure mucinous carcinomas (all P>0.05). The expression of neuroendocrine marker was stronger in hypercellular mucinous carcinoma than that in mixed mucinous carcinoma and hypocellular mucinous carcinoma (all (P<0.05), but the difference was not statistically significant between mixed mucinous carcinoma and hypocellular pure mucinous carcinoma (P>0.05). The expression of WT-1 was weaker in mixed mucinous carcinoma than that in hypercellular and hypocellular pure mucinous carcinoma(all (P<0.05), but the difference was not statistically significant between hypercellular and hypocellular pure mucinous carcinoma (P>0.05). The mucinous carcinomas with lymph node metastasis had lower expression of neuroendocrine markers than those without lymph node metastasis ((P<0.01). The expression of WT-1 in breast mucinous carcinoma with lymph node metastasis trended lower than that in those without lymph node metastasis, but the difference was not statistically significant (P>0.05). CONCLUSION: Hypercellular pure mucinous breast carcinoma has higher rates of lymph node metastasis and HER-2 amplification than hypocellular pure mucinous carcinoma, the sub-classification of breast pure mucinous carcinoma should be considered. Neuroendocrine differentiation and WT-1 expression may be helpful in distinguishing the subtypes of breast mucinous carcinoma. Breast mucinous carcinoma with neuroendocrine differentiation trends to have less lymph node metastasis.

Decreased expression of dual specificity phosphatase 22 in colorectal cancer and its potential prognostic relevance for stage IV CRC patients.

Dual specificity phosphatase 22 (DUSP22) is a novel dual specificity phosphatase that has been demonstrated to be a cancer suppressor gene associated with numerous biological and pathological processes. However, little is known of DUSP22 expression profiling in colorectal cancer and its prognostic value. Our study aims to investigate the role of DUSP22 expression in the prognosis of colorectal cancer. We detected the mRNA expression in 92 paired primary colorectal cancer tissues and the corresponding adjacent normal tissues by using QuantiGenePlex assay. The Friedman test was used to determine the statistical difference of gene expression. Kaplan-Meier survival analysis was performed. Mann-Whitney test and Kruskal-Wallis test were used to conduct data analyses to determine the prognostic value. Statistical significance was set at P < 0.05. In 74 of 92 cases, DUSP22 mRNA was reduced in primary colorectal cancer tissues, compared to the adjacent normal tissues. The mRNA levels of DUSP22 were significantly lower in colorectal cancer tissues than in adjacent normal tissues (0.0290 vs. 0.0658; P < 0.001). Low expression of DUSP22 correlated significantly with large tumor size (P = 0.013). No association was observed between DUSP22 mRNA expression and differentiation, histopathological type, tumor invasion, lymph node metastases, metastases, TNM stage, and Duke's phase (all P > 0.05). Kaplan-Meier analysis indicated that DUSP22 expression had no significant relationship with overall survival in all patients (P > 0.05). Interestingly, low expression level of DUSP22 in stage IV patients had a poor survival measures with a marginal P value (P = 0.07). Reduced DUSP22 expression was found in colorectal cancer specimens. Low expression level of DUSP22 in stage IV patients had a poor survival outcome. Further study is required for the investigation of the role of DUSP22 in colorectal cancer.

[Expression of IgG4 in Rosai-Dorfman disease and its significance].

OBJECTIVE: To study the prevalence of IgG4-positive plasma cells in Rosai-Dorfman disease and to assess the association between Rosai-Dorfman disease and IgG4-related sclerosing disease (IgG4-SD). METHODS: The clinicopathologic features of 12 tissue samples of Rosai-Dorfman disease (11 extranodal and one nodal) from nine patients were reviewed. The degree of fibrosis and occlusive phlebitis was studied by HE staining. The expression of IgG4 and IgG in plasma cells were studied by immunohistochemistry (EnVision) and quantitatively analyzed by medical image analysis system. RESULTS: Nine tissue samples showed different degree of fibrosis (four tissue samples were mild, one tissue sample was moderate and four tissue samples were severe) and two tissue samples showed occlusive phlebitis in the lesional tissue. Immunohistochemical study showed marked infiltration by IgG4-positive plasma cells (> 50 per high-power field) in four tissue samples, moderate infiltration (30 to 50 per high-power field) in two tissue samples, mild (10 to 29 per high-power field) in three cases and negative infiltration (< 10 per high-power field) in three tissue samples (P < 0.01). Three tissue samples fulfilled the diagnostic criteria of IgG4-SD (> 50 IgG4-positive plasma cells per high-power field and IgG4-to-IgG ratio > 40%), including one tissue sample each of Rosai-Dorfman disease in the left facial skin, above the left eye socket, and in the right parotid. CONCLUSIONS: Some cases of Rosai-Dorfman disease fulfill the diagnostic criteria and show the histologic features of IgG4-SD. They may represent members of the IgG4-SD spectrum. The detection of IgG4-positive plasma cells in the lesional tissues of Rosai-Dorfman disease may have clinical pathological significance.

FDG PET/CT Imaging of Liver and Spleen Histiocytic Sarcoma.

ABSTRACT: Histiocytic sarcoma is a tumor of the lymphohematopoietic system characterized by macrophage morphology and immunophenotype. Here, we report FDG PET/CT images of a 50-year-old man with coexisting histiocytic sarcoma of the liver and spleen. Images showed multiple enhanced uptake lesions of FDG in both the liver and spleen. Ultimately, histiocytic sarcoma was confirmed by the biopsy histopathology.

Retrospective analysis of cytology and high-risk HPV testing in 1067 endocervical adenocarcinomas and precursor lesions.

BACKGROUND: Cytology and high-risk human papilloma virus (hrHPV) cotesting is the mainstay in the detection of cervical carcinoma. METHODS: Endocervical adenocarcinoma (EAC) is divided into HPV-associated adenocarcinoma (HPVA) and HPV-independent adenocarcinoma (HPVI) by the World Health Organization classification (2020). The detection effect of cotesting is suggested to be different among EAC subtypes and precursors, but has not well-documented yet. In this study, the authors retrospectively analyzed cotesting among adenocarcinoma in situ (AIS), HPVA, and HPVI. The cohort included 569 AIS and 498 EAC consisting of 371 (74.5%) HPVA, 111 (22.3%) HPVI, and 16 (3.2%) adenocarcinoma, not otherwise specified. RESULTS: The authors found that AIS patients were significantly younger than HPVA and HPVI (mean ± SD, years: 40.7 ± 8.6; HPVA, 44.8 ± 9.3; HPVI, 50.0 ± 11.3; p < .001) and had a higher prevalence of concurrent squamous intraepithelial lesions (75.5%, HPVA, 37.2%; HPVI, 12.6%; p < .001). The detection rate of hrHPV test or cytology was substantially higher in AIS and HPVA than in HPVI (97.7% and 90.2% vs. 16.5%, p < .001, or 71.1% and 71.9% vs. 60.7%, p = .042, respectively). Cytology and hrHPV cotesting was superior to a single test in the detection of EAC and AIS. The detection rate of cotesting amounted to 100% in AIS and 94.3% in HPVA but was substantially lower in HPVI (72.2%) (p < .001). CONCLUSIONS: The authors conclude that cytology and hrHPV cotesting can maximize the detection effect for HPVA and AIS but is not optimal for HPVI.

Non-POEMS osteosclerotic multiple myeloma: Clinical characteristics and differential diagnosis.

Osteosclerosis in multiple myeloma (MM) is typically associated with rare POEMS syndrome, characterized by polyneuropathy (P), organomegaly (O), endocrinopathy (E), M-protein (M), and skin changes (S). However, osteosclerosis in multiple myeloma (MM) without POEMS syndrome, defined as non-POEMS Osteosclerotic MM, is exceedingly rare. We report a 70-year-old man with rib pain, remarkably high bone mineral density and diffuse osteosclerosis. The diagnosis of non-POEMS osteosclerotic MM was confirmed by biopsy and aspiration of bone marrow through surgery. A literature review spanning from 1990 identified 12 cases of similar non-POEMS osteosclerotic MM, including 5 males and 7 females with a mean age of 59.7 ± 10.6 years. The non-POEMS osteosclerotic MM can be divided into two subtypes, the osteosclerotic lesion subtype and the diffuse osteosclerosis subtype. Absence of polyneuropathy and organomegaly are the main factors that differentiate non-POEMS osteosclerotic MM from POEMS. A hyperactive osteoblastic process might be the etiology of diffuse osteosclerosis. Further research is needed to understand its etiology and pathophysiology.

Stability and function of RCL1 are dependent on the interaction with BMS1.

During ribosome biogenesis, the small subunit (SSU) processome is responsible for 40S assembly. The BMS1/RCL1 complex is a core component of the SSU processome that plays an important role in 18S rRNA processing and maturation. Genetic studies using zebrafish mutants indicate that both Bms1-like (Bms1l) and Rcl1 are essential for digestive organ development. In spite of vital functions of this complex, the mutual dependence of these two nucleolar proteins for the stability and function remains elusive. In this study, we identified an RCL1-interacting domain in BMS1, which is conserved in zebrafish and humans. Moreover, both the protein stability and nucleolar entry of RCL1 depend on its interaction with BMS1, otherwise RCL1 degraded through the ubiquitination-proteasome pathway. Functional studies revealed that overexpression of RCL1 in BMS1-knockdown cells can partially rescue the defects in 18S rRNA processing and cell proliferation, and hepatocyte-specific overexpression of Rcl1 can resume zebrafish liver development in the bms1l substitution mutant bms1lsq163/sq163but not in the knockout mutant bms1lzju1/zju1, which is attributed to the nucleolar entry of Rcl1 in the former mutant. Our data demonstrate that BMS1 and RCL1 interaction is essential for not only pre-rRNA processing but also the communication between ribosome biogenesis and cell cycle regulation.

A deep learning model based on MRI for prediction of vessels encapsulating tumour clusters and prognosis in hepatocellular carcinoma.

PURPOSE: This study aimed to build and evaluate a deep learning (DL) model to predict vessels encapsulating tumor clusters (VETC) and prognosis preoperatively in patients with hepatocellular carcinoma (HCC). METHODS: 320 pathologically confirmed HCC patients (58 women and 262 men) from two hospitals were included in this retrospective study. Institution 1 (n = 219) and Institution 2 (n = 101) served as the training and external test cohorts, respectively. Tumors were evaluated three-dimensionally and regions of interest were segmented manually in the arterial, portal venous, and delayed phases (AP, PP, and DP). Three ResNet-34 DL models were developed, consisting of three models based on a single sequence. The fusion model was developed by inputting the prediction probability of the output from the three single-sequence models into logistic regression. The area under the receiver operating characteristic curve (AUC) was used to compare performance, and the Delong test was used to compare AUCs. Early recurrence (ER) was defined as recurrence within two years of surgery and early recurrence-free survival (ERFS) rate was evaluated by Kaplan-Meier survival analysis. RESULTS: Among the 320 HCC patients, 227 were VETC- and 93 were VETC+ . In the external test cohort, the fusion model showed an AUC of 0.772, a sensitivity of 0.80, and a specificity of 0.61. The fusion model-based prediction of VETC high-risk and low-risk categories exhibits a significant difference in ERFS rates, akin to the outcomes observed in VETC + and VETC- confirmed through pathological analyses (p < 0.05). CONCLUSIONS: A DL framework based on ResNet-34 has demonstrated potential in facilitating non-invasive prediction of VETC as well as patient prognosis.

Perioperative cimetidine administration improves systematic immune response and tumor infiltrating lymphocytes in patients with colorectal cancer.

BACKGROUND/AIMS: Cimetidine has been shown to play an important role in the treatment of cancer and the regulation of the immune system. Therefore, we aimed to observe the effects of cimetidine on the systematic immune response in the perioperative period. METHODOLOGY: Sixty patients with colorectal cancer were enrolled from Jan 2005 to Dec 2005 from Taizhou Hospital. The patients were administrated with cimetidine (0.8 g.d-1 or 1.2 g.d-1) or saline from the day of admission to the 10th POD. Venous blood sample was collected and the T-, B- and NK-lymphocyte subsets were determined by flow cytometry. The specimens were subjected to tumor-infiltrating lymphocytes (TILs) response examination. RESULTS: The levels of CD3 and CD4 T-lymphocytes were increased significantly in both low and high dose cimetidine groups 10 days after operation. The number of CD19 B cells was also elevated by cimetidine. However, no significant changes were observed in the CD8, CD4/CD8 value. TIL responses in the cimetidine groups were also enhanced significantly. CONCLUSIONS: Cimetidine can alleviate systematic immunosuppression and improve the local immune function of the colorectal cancer patients in the perioperative period.

Next-generation sequencing shows the genomic features of ovarian clear cell cancer and compares the genetic architectures of high-grade serous ovarian cancer and clear cell carcinoma in ovarian and endometrial tissues.

Ovarian clear cell carcinoma (OCCC) is a special histological type of epithelial ovarian cancer (EOC) that is not derived from epithelial cells of the ovarian or fallopian tube as the most common type of ovarian cancer, high-grade serous ovarian carcinoma (HGSOC), but is closely related to endometriosis and similar to endometrial clear cell carcinoma (ECCC) at morphologic and phenotypic features. However, limited data was shown in OCCC genomic features and compared with that in OCCC, HGSOC and ECCC. Herein, we utilized next-generation sequencing analysis of a panel of 1,021 genes to profile the mutational alterations in 34 OCCC and compared them to those from HGSOC (402 cases) and ECCC (30 cases). In result, the ARID1A and PIK3CA are high-frequency mutations of OCCC. Clonal architectures showed that all the mutations of genes occur in the later stage in the OCCC progress, whereas KRAS mutation is the earlier event compared with mutation of ARID1A or PIK3CA, which usually occurs in a group of ARID1A or PIK3CA mutations. The mutation frequency of main driver genes is similar between OCCC and ECCC, while TP53 is the main mutation in HGSOC and ECCC. Shared mutational signatures between OCCC and ECCC tissues with commonly observed a C>T change indicated a common carcinogens-exposed between these two carcinomas, but HGSOC and ECCC have common and distinct mutational signatures across cohorts respectively. In addition, we identified some novel CNV gains in NF1, ASXL1, TCF7L2, CREBBP and LRP1B and loss in ATM, FANCM, RB1 and FLT in OCCC. Our study offered a new perspective for OCCC tumorigenesis from two organs, the ovary and uterus, at genomic architectures and revealed novel CNV events for helping to provide theoretical support for OCCC treatment.

KDF1 Promoted Proliferation, Migration and Invasion of Lung Adenocarcinoma Cells through Activating STAT3 and AKT Pathway.

KDF1 has been reported to be correlated with carcinogenesis. However, its role and mechanism are far from clear. To explore the possible role and underlying mechanism of KDF1 in lung adenocarcinoma (LUAD), we investigated KDF1 expression in LUAD tissues and the influence of KDF1 in the phenotype of LUAD cells (A549 and PC-9) as well as the underlying mechanism. Compared to non-tumor lung epithelial cells, KDF1 was upregulated in the cancer cells of the majority of LUAD patients, and its expression was correlated with tumor size. Patients with enhanced KDF1 in cancer cells (compared with paired adjacent non-neoplastic lung epithelial cells) had shorter overall survival than patients with no increased KDF1 in cancer cells. Knockdown of KDF1 inhibited the migration, proliferation and invasion of LUAD cells in vitro. And overexpression of KDF1 increased the growth of the subcutaneous tumors in mice. In terms of molecular mechanisms, overexpression of KDF1 induced the expression of AKT, p-AKT and p-STAT3. In KDF1-overexpressing A549 cells, inhibition of the STAT3 pathway decreased the level of AKT and p-AKT, whereas inhibition of the AKT pathway had no effect on the activation of STAT3. Inhibition of STAT3 or AKT pathways reversed the promoting effects of KDF1 overexpression on the LUAD cell phenotype and STAT3 inhibition appeared to have a better effect. Finally, in the cancer cells of LUAD tumor samples, the KDF1 level was observed to correlate positively with the level of p-STAT3. All these findings suggest that KDF1, which activates STAT3 and the downstream AKT pathway in LUAD, acts as a tumor-promoting factor and may represent a therapeutic target.

An inflammation-related signature could predict the prognosis of patients with kidney renal clear cell carcinoma.

Background: Kidney renal clear cell carcinoma (KIRC) is an inflammation-related carcinoma, and inflammation has been recognized as an important factor in inducing carcinogenesis. To further explore the role of inflammation in KIRC, we developed an inflammation-related signature and verified its correlation with the tumor micro-environment. Methods: After the differential inflammation-related prognostic genes were screened by Lasso regression, the inflammation-related signature (IRS) was constructed based on the risk score of multivariate Cox regression. Then, the prognostic value of the IRS was evaluated by Kaplan-Meier analysis, receiver operating characteristic (ROC) curve analysis and multivariate Cox regression. Gene set variation analysis (GSVA) was applied to screen out enriched signaling pathways. Infiltrated immune cells, tumor mutational burden (TMB) and immune checkpoints were explored by CIBERSORTx and maftool. Results: Four genes (TIMP1, PLAUR, CCL22, and IL15RA) were used to construct the IRS in patients with KIRC. Kaplan-Meier analysis and multivariate Cox regression identified that the IRS could independently predict the prognosis of patients with KIRC in the training and validation groups. The diagnostic value of the nomogram increased from 0.811 to 0.845 after adding the IRS to the multiparameter ROC analysis. The GSVA results indicated that IRS was closely related to primary immunodeficiency and antigen processing and presentation. The immune checkpoint LAG3 was highly expressed in patients with high-risk score (p < 0.05), while CD274 (PD-L1) and HAVCR2 were highly expressed in patients with low-risk score (p < 0.001). There was a significant positive correlation between the high-risk score group and CD8+ T, activated CD4+ memory T, gamma and delta regulatory T and M0 macrophage cells, while the low-risk score group was negatively associated with B memory, plasma, resting CD4+ memory T, activated NK, M1 macrophages and resting mast cells. Conclusion: We found that the IRS might serve as a biomarker to predict the survival of KIRC. Moreover, patients with high or low-risk score might be sensitive to immune drugs at different immune checkpoints.

Molecular landscape and therapeutic alterations in Asian soft-tissue sarcoma patients.

BACKGROUND: Soft-tissue sarcoma (STS) is a rare solid malignant tumor with numerous histologic subtypes. Current studies on targeted therapy for STS are in preclinical and early-phase trials. Genomic differences largely influence the prognosis of patients even with the same subtype. To investigate the genomic alterations (GAs) and the potential of targeted therapy in STS, we analyzed the genomic landscape, the therapeutic GAs, and biomarkers of immunotherapy in Chinese STS patients. METHODS: Targeted sequencing covering 425 genes was performed, from which we obtained the results of tissue samples from 351 Chinese STS patients of all ages covering different histologic subtypes. Bioinformatics analysis of altered genes with nonsynonymous mutations, copy-number variations, and gene fusions were performed. OncoKB therapeutic GAs and relevant biomarkers including TMB, MSI, and HRD were further examined for potential targeted therapy. RESULTS: In total, 2743 GAs were identified in 330 genes with a median of 6 (1-38) per case. The top 11 frequently altered genes were: TP53, MCL1, MDM2, CDK4, MYC, CDKN2A, GNAS, RB1, ATRX, CDKN2B, and FGFR1. OncoKB defined therapeutic GAs were found in 23 genes in 43% of the patients. In general, 9.4% of the patients had high-TMB, 2.8% had MSI, and 13.7% had HRD. A significant difference in the percentage of patients with OncoKB therapeutic GAs were observed between the most frequent two subtypes, leiomyosarcoma and liposarcoma. Altogether, 54% of the patients had the potential to respond to a targeted therapy. CONCLUSION: This study indicated the potential efficacy of targeted therapy on many STS patients, and also provided insight for novel precision therapy. The clinical efficacy of combining targeted therapy and immunotherapy can be further investigated.

Choriocarcinoma Masquerading as Lung Abscess or Lung Cancer: A Case with Atypical Imaging Findings.

BACKGROUND: Choriocarcinoma is a highly malignant trophoblastic tumor. However, the awareness surrounding its atypical clinical presentation is insufficient. The presence of a solitary lung lesion without uterine lesions often leads to misdiagnosis or missed diagnosis, which in turn causes delayed treatment or even multiple metastases throughout the body. CASE PRESENTATION: We present the case of a 36-year-old female patient who was misdiagnosed with a lung abscess and received suboptimal anti-infective treatment. She then underwent left upper lobectomy and was misdiagnosed with lung cancer by abscess incision and drainage in thoracic surgery, however, the results after pleural effusion removal were suboptimal. During this time a breast nodule was found, and a large segment of the right breast was excised and misdiagnosed as breast cancer but was finally diagnosed as choriocarcinoma with multiple metastases of lung and breast. Multiple metastases were also detected in the head, liver, kidney, and bones. The patient underwent multiple adjuvant chemotherapies. The blood ß-hCG level gradually declined to normal. When we reported this case, that is, seven months after the diagnosis, the patient was still alive, and the disease was stable without progress. CONCLUSION: Choriocarcinoma with a solitary lung lesion as the first presentation and no lesions in the uterus is clinically rare. This may lead to a delay in diagnosis due to poor awareness of the disease and the appearance of multiple metastases throughout the body. Clinicians should be more aware of choriocarcinoma with an atypical presentation to reduce misdiagnosis and missed diagnosis.