Poor Tumor Differentiation Research Articles

Effects of Adjuvant Chemotherapy on Oncologic Outcomes in Patients With Stage ⅡA Rectal Cancer Above the Peritoneal Reflection Who Did Not Undergo Preoperative Chemoradiotherapy

PurposeThis study aimed to evaluate the effects of adjuvant chemotherapy (AC) on oncologic outcomes for patients with stage IIA upper rectal cancer and to investigate whether AC is associated with improved survival outcomes. MethodsThis retrospective study comprised 432 patients with rectal cancer above the peritoneal reflection who had undergone curative resection without preoperative chemoradiotherapy between 2008 and 2016. This study cohort was divided according to whether AC was received (AC group) or not (no-AC group). Risk factors included obstruction, perforation, poorly-differentiated tumor, lympho-vascular invasion, perineural invasion, resection margin involvement, and < 12 lymph nodes harvested. ResultsAmong the 432 patients, 279 (64.6%) had received AC. The AC group had significantly higher 5-year overall survival (OS) rates than those of the no-AC group (93.2% vs. 84.6%, P = .001). Among patients with ≥ 1 risk factors, the AC group (n = 123) had significantly higher rates of 5-year recurrence-free survival (RFS) (81.6% vs. 64.1%, P = .01) and 5-year OS (88.8% vs. 69.0%, P = .001) than those of the no-AC group (n = 59). No significant difference in survival outcomes was observed between the 2 groups in patients aged > 65 years. ConclusionAC was significantly associated with better 5-year RFS and 5-year OS rates in patients with stage IIA rectal cancer above peritoneal reflection who did not receive preoperative chemoradiotherapy, especially in those with ≥ 1 risk factors.

Epidemiology of Adenosquamous Carcinomas.

Adenosquamous carcinomas (ASCs) are a very rare histology containing cancer cells with both glandular-like (adeno) and squamous cell histologies, comprising typically a fraction of a percent of all solid tumors. The bulk of the literature on ASCs is comprised of case reports and small series, with the general finding that ASCs tend to have worse outcomes than either of their parent histologies. However, there is a lack of pan site-comparative studies in the literature that compare ASC clinicodemographic and survival outcomes with those of conventional adenocarcinomas (ACs) and squamous cell carcinomas (SCCs). In this study, we summarize these outcomes in eight primary sites, comprising 92.7% of all ASC cases diagnosed from 1975 to 2020 in the Surveillance, Epidemiology, and End Results (SEER) database. Lung ASCs comprise 51.5% of all ASC cases, accounting for 1.1% of all lung cancer cases, followed by uterine/cervical cancers at 29.7% of all ASC cases, translating into 1.8% of all cancers in this site. In descending order, the remaining 20% of ASCs arise in pancreatic, oral cavity, biliary, esophageal, colorectal, and gastric sites, comprising between 0.1% and 0.7% of all cancers in these sites. Apart from pancreatic and oral cavity cancers, ASC tumors tended to favor higher rates of regional or distant disease at presentation with poor tumor differentiation compared to either AC or SCC histologies. After multivariable analysis, adjusting for age, sex, detection stage, grade differentiation, surgery, chemotherapy, and radiotherapy, except for oral cavity cancers, ASCs tended to have worse overall survivals compared to ACs (hazard ratios: 1.1 - 1.6) and SCC (1.0 - 1.3), with colorectal ASCs having the worse overall survival compared to colorectal ACs, with a hazard ratio of 1.4 (95% confidence interval: 1.3 - 1.6). Overall, these results suggest that ASC outcomes are site specific, and in general, tend to have worse outcomes than nonvariant ACs and SCCs even after correction for common clinical and epidemiological factors. These cancers have a poorly understood but unique tumor biology that warrants further characterization.

Value of the HOTAIR expression assay in predicting therapy target in hepatocellular carcinoma: A meta-analysis and bioinformatics analysis.

Several studies show that the long non-coding RNA HOX transcript antisense RNA (HOTAIR) was upregulated in human cancer, which was associated with several clinical features and may have the potential to be prognostic markers. However, the significance of HOTAIR in hepatocellular carcinoma remains unclear. We performed a meta-analysis and bioanalysis to further investigate the association between HOTAIR and hepatocellular carcinoma. Eligible literature was systematically retrieved from PubMed, Embase, and Web of Science databases. The pooled hazard ratios with 95% confidence intervals were used to evaluate to the effect. Raw data on HOTAIR expression were obtained from The Cancer Genome Atlas data portals. All bioinformatics analyses were performed using R software (version 4.3.1). We identified eight studies in this meta-analysis with a total of 399 patients. High-level HOTAIR expression was found to be significantly related to advanced tumor node metastasis stage, distant metastasis, poor tumor differentiation, and patients with hepatitis. Correspondingly, HOTAIR was also associated with poor overall survival and relapse-free survival. Subsequently, in bioanalysis, HOTAIR expression was higher in hepatocellular carcinoma as well as poor overall survival. High HOTAIR expression was strongly correlated with tumor node metastasis stage. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the differentially expressed genes related to HOTAIR may be involved in the cancer-associated signaling pathway. HOTAIR may be a potential biomarker for HCC prediction and is expected to become a new choice for clinical HCC prediction..

Risk of recurrence in high-risk T1 colon cancer following endoscopic and surgical resection: registry-based cohort study.

Endoscopic resection of T1 colon cancer (CC) is currently limited by guidelines related to risk of lymph node metastases. However, clinical outcome following endoscopic and surgical resection is poorly investigated. A retrospective multicentre national cohort study was conducted on prospectively collected data from the Swedish colorectal cancer registry on all non-pedunculated T1 CC patients undergoing surgical and endoscopic resection between 2009 and 2021. Patients were categorized on the basis of deep submucosal invasion (Sm2-3), lymphovascular invasion (LVI), poor tumour differentiation, and R1/Rx into low- and high-risk cases. The primary outcomes of interest were recurrence rates and disease-free interval (DFI, defined as time from treatment to date of recurrence) according to resection methods and risk factors (sex, age at diagnosis, histologic grade, LVI, perineural invasion, mucinous subtype, submucosal invasion, tumour location, resection margin and nodal positivity in the surgical group). In total, 1805 patients undergoing endoscopic (488) and surgical (1317) resection with 60.0 months median follow-up were included. Recurrence occurred in 18 (3.7%) endoscopically and 48 (3.6%) surgically resected patients. Adjuvant treatment was administered in 7.4% and 0.2% of the cases respectively in the surgical and endoscopically treated patients. Five-year DFI was 95.6% after endoscopic and 96.2% after surgical resection, with no significant difference when adjusting for confounding factors (HR 1.03, 95% c.i. 0.56 to 1.91, P = 0.920). There were no statistically significant differences in recurrence comparing endoscopic (1.7%) versus surgical (3.6%) low-risk and endoscopic (5.4%) versus surgical (3.8%) high-risk cases. LVI was the only significant risk factor for recurrence in multivariate Cox regression (HR 3.73, 95% c.i. 1.76 to 7.92, P < 0.001). This study shows no difference in recurrence after endoscopic and surgical resection in high-risk T1 CC. Although it was not possible to match groups according to treatment, the multivariate analysis showed that lymphovascular invasion was the only independent risk factor for recurrence.

Abstract PO3-15-01: Overexpression of N-glycosylation related gene OST4 promotes chemotherapy resistance in triple-negative breast cancer

Abstract Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, with high malignancy and poor outcome. Resistance to chemotherapy leads to treatment failure. How to overcome drug resistance is the key point in TNBC treatment. Previously, we initiated a prospective multicenter single-arm NeoPath clinical study (ClinicalTrial.gov identifier: NCT03907800) to assess the efficacy and safety of nab-paclitaxel combined with carboplatin in the neoadjuvant therapy of triple negative and HER2-positive early breast cancer. A total of 99 TNBC patients were enrolled and the pCR rate in TNBC was 33.78%. Samples before and after treatment were collected. RNA-sequencing results showed that OST4 was of high-expression in drug-resistant TNBC tumor tissues compared with chemo-sensitive samples. To verify the clinical significance of OST4 expression levels in TNBC, we tested the expression of OST4 by immunohistochemical technique on a tissue microarray including 87 TNBC cases treated with chemotherapy. We found that high expression of OST4 was associated with poor tumor differentiation, and patients with high OST4 expression had more relapse after chemotherapy. Ex-vivo proliferation assay and foci formation assay further confirmed that over-expression of OST4 promoted chemo-resistance, whereas down-regulating OST4 could reverse resistance in TNBC cell lines. As an oligosaccharyltransferase, it is reported that OST4 played parts in N-glycosylation. So we try to elucidate the relationship between N-glycosylation and drug resistance. Glycoproteomics results verified the existence of differential N-glycosylation atlas in drug-resistant tumor tissues compared with drug sensitive samples. NGS1 was identified as a potential target of OST4 by co-immunoprecipitation and mass spectrometry. In conclusion, high expression of OST4 could promote chemotherapy resistance in TNBC trough N-glycosylation regulation. Targeting OST4 may help reverse drug-resistance and improve therapeutic effect in TNBC. Citation Format: Wei Wang, Deyue Liu, Shuning Ding, Yan Fang, Jiayi Wu, Li Zhu. Overexpression of N-glycosylation related gene OST4 promotes chemotherapy resistance in triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-15-01.

HHLA2 promotes hepatoma cell proliferation, migration, and invasion via SPP1/PI3K/AKT signaling pathway.

Hepatocellular carcinoma (HCC) stands as one of the most malignant tumors characterized by poor prognosis and high mortality rates. Emerging evidence underscores the crucial role of the B7 protein family in various cancers, including HCC. However, the involvement of the human endogenous retrovirus H long-terminal repeat-associated protein 2 (HHLA2,or B7-H5) in HCC remains unclear.Immunohistochemistry was employed to assess the differential expression of HHLA2 between HCC and normal liver tissues. A battery of assays, including CCK8, EdU, tablet clone-forming, Transwell, and wound healing assays, were conducted to elucidate the function and potential mechanisms of HHLA2 in the malignant biological behaviors of HCC. Additionally, a xenograft mouse model was established to evaluate the tumorigenicity of hepatoma cell lines exhibiting different HHLA2 expression levels in vivo. Western blot analysis was used to analyze HHLA2, secretory phosphoprotein 1 (SPP1), and PI3K/AKT/mTOR levels.HHLA2 exhibited elevated expression in HCC tissues, correlating with poor tumor differentiation and shortened overall survival in HCC patients. In vitro experiments demonstrated that HHLA2 overexpression (OE) promoted the proliferation, migration, and invasion of hepatoma cells, while in vivo experiments revealed that HHLA2 OEenhanced HCC tumor growth. Conversely, inhibition of HHLA2 expression yielded the opposite effect. Downregulation of SPP1 inhibited the proliferation, migration, and invasion induced by HHLA2 OE, and this effect was linked to the PI3K/AKT/mTOR signaling pathway.Our findings indicate that HHLA2 promotes the proliferation, migration, and invasion of hepatoma cells via the SPP1/PI3K/AKT signaling pathway, establishing it as a potential therapeutic target for HCC.

Limited Role of the Apparent Diffusion Coefficient (ADC) for Tumor Grade and Overall Survival in Resectable Pancreatic Ductal Adenocarcinoma.

This study evaluated the relationship between apparent diffusion coefficient (ADC) values in pancreatic ductal adenocarcinoma (PDAC) and tumor grades based on WHO, Adsay, and Kalimuthu classifications, using whole-mount pancreatectomy specimens. If glandular formation plays a key role in the degree of diffusion restriction, diffusion-weighted imaging could facilitate non-invasive grading of PDAC. A freehand region of interest (ROI) was drawn along tumor borders on the preoperative ADC map in each tumor-containing slice. Resection specimens were retrospectively graded according to WHO, Adsay, and Kalimuthu classifications and correlated with overall survival and the 10th percentile of whole-volume ADC values. Findings from 40 patients (23 male, median age 67) showed no correlation between ADC p10 values and WHO differentiation (p = 0.050), Adsay grade (p = 0.955), or Kalimuthu patterns (p = 0.117). There was no association between ADC p10 and overall survival (p = 0.082) and other clinicopathological variables. Survival was significantly lower for poor tumor differentiation (p = 0.046) and non-glandular Kalimuthu patterns (p = 0.016) and there was a trend towards inferior survival for Adsay G3 (p = 0.090) after correction for age, tumor location, and stage. Preoperative ADC measurements for determining PDAC aggressiveness had limited clinical utility, as there was no correlation with histological parameters or overall survival in resectable PDAC.

Methylation of NRIP3 Is a Synthetic Lethal Marker for Combined PI3K and ATR/ATM Inhibitors in Colorectal Cancer.

The aim of this study was to investigate the epigenetic regulation and underlying mechanism of NRIP3 in colorectal cancer (CRC). Eight cell lines (SW480, SW620, DKO, LOVO, HT29, HCT116, DLD1, and RKO), 187 resected margin samples from colorectal cancer tissue, 146 cases with colorectal adenomatous polyps, and 308 colorectal cancer samples were used. Methylation-specific PCR, Western blotting, RNA interference assay, and a xenograft mouse model were used. NRIP3 exhibited methylation in 2.7% (5/187) of resected margin samples from colorectal cancer tissue, 32.2% (47/146) of colorectal adenomatous polyps, and 50.6% (156/308) of CRC samples, and the expression of NRIP3 was regulated by promoter region methylation. The methylation of NRIP3 was found to be significantly associated with late onset (at age 50 years or older), poor tumor differentiation, lymph node metastasis, and poor 5-year overall survival in CRC (all P < 0.05). In addition, NRIP3 methylation was an independent poor prognostic marker ( P < 0.05). NRIP3 inhibited cell proliferation, colony formation, invasion, and migration, while induced G1/S arrest. NRIP3 suppressed CRC growth by inhibiting PI3K-AKT signaling both in vitro and in vivo . Methylation of NRIP3 sensitized CRC cells to combined PI3K and ATR/ATM inhibitors. NRIP3 was frequently methylated in both colorectal adenomatous polyps and CRC. The methylation of NRIP3 may potentially serve as an early detection, late-onset, and poor prognostic marker in CRC. NRIP3 is a potential tumor suppressor. NRIP3 methylation is a potential synthetic lethal marker for combined PI3K and ATR/ATM inhibitors.

Downregulation of INPP4B is Associated with Poor Prognosis in Epithelial Ovarian Carcinoma.

INPP4B is a tyrosine-specific phosphatase in the human body, which plays an important role in the developing process of carcinogenesis. However, The correlation between INPP4B and epithelial ovarian cancer is rarely explored. In this study, the expression of INPP4B in human epithelial ovarian carcinoma and normal ovaries was detected, to explore the correlation between INPP4B expression and clinicopathological risk factors of epithelial ovarian carcinoma and to clarify its significance in the developing process of and prognosis of epithelial ovarian carcinoma. The expression of INPP4B in various tumors was detected by bioinformatics method, and the expression in epithelial ovarian cancer and normal control group was detected by Elisa. The immunohistochemical method was used in this experiment to analyze the expression of INPP4B in specimens of 100 cases of epithelial ovarian carcinoma and 20 cases of normal ovaries. Analysis of clinicopathological risk factors and related survival analysis was carried out on the expression of INPP4B in 100 cases of epithelial ovarian carcinoma. The results showed that the positive expressed INPP4B protein in epithelial ovarian carcinoma was significantly less, compared with that in normal ovaries (P < 0.05). The expression of INPP4B was significantly associated with many clinicopathologic factors, such as tumor differentiation (P < 0.001), FIGO stage (P < 0.001), lymph node metastasis (P < 0.001) and distant metastasis at recurrence (P=0. 009), but not with age, pathologic type of tumor, serum CA125 at recurrence and chemotherapy sensitivity. In epithelial ovarian carcinoma, there is a downregulation of INPP4B expression, which may be related to poor tumor differentiation, late FIGO stage, lymph node metastasis, distant metastasis at recurrence and insensitivity to chemotherapy. Under-expression of INPP4B, lymph node metastasis, FIGO stage, and distant metastasis at recurrence are factors of poor prognostic. The under-expression level of INPP4B may be involved in the progression of epithelial ovarian carcinoma.

A Study of the Prognostic Factors for Late Cervical Lymph Node Metastasis and Distant Metastasis in Patients with cT1-2N0 Tongue Cancer.

Background: Early-stage tongue cancer has a good prognosis in general; however, high-risk patients with late cervical lymph node and distant metastases have a poor prognosis. Elective neck dissection and postoperative chemoradiotherapy are considered for these patients, although no clear criteria have been identified for their evaluation. Methods: This retrospective observational study aimed to determine the predictive factors for late cervical lymph node and distant metastases in 102 patients with cT1-2N0 tongue cancer. The data regarding the demographic characteristics, as well as the depth of invasion, tumor budding, histological grade, and tumor-stromal ratio, among other things, were extracted from medical records. Results: We found that the potential lymph node metastasis rate was 27.5%. The significant clinical predictors of late cervical lymph node metastasis were the tumor thickness and endophytic growth pattern and the significant histopathological factors were poorly and moderately differentiated tumors and ≥3 tumor buds. In addition, the prognostic factors for distant metastasis included ≥4 lymph node metastases, ≥7 tumor budding, and moderate and poor tumor differentiation. Conclusions: The usefulness of tumor budding as a predictor of metastasis for tongue cancer was suggested. The findings of this study can help establish the criteria for evaluating the metastasis risk and prognosis of patients with tongue cancers.

HER2 in Gastric Cancer: A Comprehensive Analysis Combining Meta-Analysis and DCE-MRI Radiomics.

Advanced gastric cancer (AGC) is a severe malignant tumor, and overexpression of HER2/ERBB2 may play a crucial role in its development. The purpose of this study is to investigate the overexpression of HER2/ERBB2 in gastric cancer through a meta-analysis and examine its relationship with perfusion parameters using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) technology. We conducted an extensive literature search and collected relevant studies for the meta-analysis. We used a random-effects model and assigned weights using the "inverse variance" method. Additionally, we included 95 AGC patients diagnosed pathologically between April 2018 and October 2021. They all underwent DCE-MRI scans, and the data were subsequently analyzed using the Omni kinetic software. HER2 expression was assessed using immunohistochemistry. The meta-analysis revealed an overall odds ratio (OR) of .21 for HER2/ERBB2 overexpression in gastric cancer, with a 95% confidence interval of [.14, .30]. DCE-MRI results showed a significant association between high HER2 expression and poor tumor differentiation (P < .005). The extracellular volume fraction (Ecv) quantile, mean, relative deviation, median intensity, and difference entropy were significantly higher in the low HER2 expression group compared to the high HER2 expression group. Receiver operating characteristic (ROC) curve analysis demonstrated that the area under the curve (AUC) values of DCE-MRI radiomic parameters with significant differences were close to .7. Overexpression of HER2/ERBB2 in gastric cancer is significantly associated with certain radiomic parameters of DCE-MRI, providing a valuable diagnostic tool for clinical practice. Furthermore, the meta-analysis further confirmed the critical role of HER2/ERBB2 in the development of gastric cancer.

Expression of deiodinases-3 in HCC as predictor of poor tumor differentiation

Expression of deiodinases-3 in HCC as predictor of poor tumor differentiation

Feasibility of laparoscopic versus open pancreatoduodenectomy following neoadjuvant chemotherapy for borderline resectable pancreatic cancer: a retrospective cohort study

BackgroundThere is no evidence supporting the feasibility of laparoscopic pancreaticoduodenectomy (LPD) compared to open pancreatoduodenectomy (OPD) following neoadjuvant chemotherapy (NACT) for pancreatic ductal adenocarcinoma (PDAC).MethodsThe clinical data of consecutive patients with borderline resectable PDAC who received NACT and underwent either LPD or OPD between January 2020 and December 2022 at Fudan University Shanghai Cancer Center was prospectively collected and retrospectively analyzed.ResultsThe analysis included 57 patients in the OPD group and 20 in the LPD group. Following NACT, the LPD group exhibited a higher median CA19-9 decrease rate compared to the OPD group (85.3% vs. 66.9%, P = 0.042). Furthermore, 3 anatomically borderline PDACs in the LPD group and 5 in the OPD group were downstaged into resectable status (30.0% vs. 12.3%, P = 0.069). According to RECIST criteria, 51 (66.2%) patients in the entire cohort were evaluated as having stable disease. The median operation time for the LPD group was longer than the OPD group (419 vs. 325 min, P < 0.001), while the venous resection rate was 35.0% vs. 43.9%, respectively (P = 0.489). There was no difference in the number of retrieved lymph nodes, with a median number of 18.5 in the LPD group and 22 in the OPD group, and the R1 margin rate (15.0% vs. 12.3%) was also comparable. The incidence of Clavien-Dindo complications (35.0% vs. 66.7%, P = 0.018) was lower in the LPD group compared to the OPD group. Multivariable regression analysis revealed that a tumor diameter > 3 cm before NACT (HR 2.185) and poor tumor differentiation (HR 1.805) were independent risk factors for recurrence-free survival, and a decrease rate of CA19-9 > 70% (OR 0.309) was a protective factor for early tumor recurrence and overall survival.ConclusionsLPD for PDAC following NACT is feasible and oncologically equivalent to OPD. Effective control of CA19-9 levels is beneficial in reducing early tumor recurrence and improving overall survival.

An MRI radiomics-based model for the prediction of invasion of the lymphovascular space in patients with cervical cancer.

Cervical cancer (CC) remains the second leading cause of cancer-related death in women, and the ability to accurately anticipate the presence or absence of lymphovascular space invasion (LVSI) is critical to maintaining optimal patient outcomes. The objective of this study was to establish and verify an MRI radiomics-based model to predict the status of LVSI in patients with operable CC. The current study performed a retrospective analysis, with 86 patients in the training cohort and 38 patients in the testing group, specifically focusing on patients with CC. The radiomics feature extraction process included ADC, T2WI-SPAIR, and T2WI sequences. The training group data were used for the initial radionics-based model building, and the model predictive performance was subsequently validated using data from patients recruited in the experimental group. The development of the radiomics scoring model has been completed with 17 selected features. The study found several risk factors associated with LVSI. These risk factors included moderate tumor differentiation (P = 0.005), poor tumor differentiation (P = 0.001), and elevated combined sequence-based radiomics scores (P = 0.001). Radiomics scores based on predictive model, combined sequences, ADC, T2WI-SPAIR, and T2WI exhibited AUCs of 0.897, 0.839, 0.815, 0.698, and 0.739 in the training cohort, respectively, with corresponding testing cohort values of 0.833, 0.833, 0.683, 0.692, and 0.725. Excellent consistency was shown by the calibration curve analysis, which showed a higher degree of agreement between the actual and anticipated LVSI status. Moreover, the decision curve analysis outcomes demonstrated the medical application of this prediction model. This investigation indicated that the MRI radiomics model was successfully developed and validated to predict operable CC patient LVSI status, attaining high overall diagnostic accuracy. However, further external validation and more deeper analysis on a larger sample size are still needed.

Cancer-Derived Immunoglobulin G and Pancreatic Cancer.

Immunoglobulin (Ig) is traditionally believed to be produced solely by B cells. Nonetheless, mounting evidence has demonstrated that various types of Igs are extensively expressed in many cell types. Among them, IgG is found to be highly expressed in cancer cells and is thus labeled as cancer-derived IgG. Cancer-derived IgG shares identical fundamental structures with B cell-derived IgG, but displays several unique characteristics, including restricted variable region sequences and unique glycosylation modifications for those expressed by epithelial cancers. Cancer-derived IgG plays multiple crucial roles in carcinogenesis, including facilitating cancer invasion and metastasis, enhancing cancer stemness, contributing to chemoresistance, and remodeling the tumour microenvironment. Recent studies have discovered that cancer-derived sialylated IgG (SIA-IgG) is extensively expressed in pancreatic cancer cells and is predominantly located in the cytoplasm and on the cell membrane. Cancer-derived IgG expressed by pancreatic cancer presents a restrictive variable region sequence and contains a unique sialylation site of the Fab region. Functionally, cancer-derived IgG participates in pancreatic cancer progression via different mechanisms, such as promoting proliferation, facilitating migration and invasion, resisting apoptosis, inducing inflammation, and modulating the tumour microenvironment. SIA-IgG has shown potential as a clinical biomarker. The expression of SIA-IgG is associated with poor tumour differentiation, metastasis, and chemoresistance in pancreatic cancer. High expression of SIA-IgG can serve as an independent prognostic factor for pancreatic cancer. Additionally, SIA-IgG expression elevated with malignant progression for the precursor lesions of pancreatic cancer. These findings present a prospect of applying cancer-derived IgG as a novel diagnostic and therapeutic target in the management of pancreatic cancer, and aiding in overcoming the challenge in the treatment of this stubborn malignancy.

Parenchymal-sparing anatomical hepatectomy based on portal ramification of the right anterior section: A prospective multicenter experience with short-term outcomes.

Parenchymal-sparing anatomical hepatectomy (Ps-AH) based on portal ramification of the right anterior section (RAS) is a new technique to avoid unnecessarily transecting too much liver parenchyma, especially in cases of major anatomical hepatectomy. We prospectively assessed 26 patients with primary hepatic malignancies having undergone major Ps-AH based on portal ramification of the RAS from August 2018 to August 2022 (48 months). The perioperative indications, clinical data, intra-operative index, pathological postoperative specimens, postoperative complications, and follow-up results were retrospectively evaluated. Among the 26 patients analyzed, there was just one case that had intrahepatic cholangiocarcinoma The preoperative level of α-Fetoprotein was 25.2 ng/mL. All cases (100%) had Child-Pugh A liver function preoperatively. The ventral/dorsal RAS was preserved in 19 and 7 patients, respectively. The mean surgical margin was 6.2 mm. The mean surgical time was 228.5 minutes, while the mean blood loss was 255 mL. In pathology, 5 cases (19.2%) had microvascular invasion, and in the group of HCC patients, 92% of all cases had moderate or poor tumor differentiation. Six cases (23.1%) of postoperative complications were graded over III according to the Clavien-Dindo system, including in three patients resistant ascites or intra-abdominal abscess that required intervention. Parenchymal-sparing anatomical hepatectomy based on portal ramification of the RAS to achieve R0-resection was safe and effective, with favorable short-term outcomes. This technique can be used widely in clinical practice.

Machine Learning of Histopathological Images Predicts Recurrences of Resected Pancreatic Ductal Adenocarcinoma With Adjuvant Treatment.

Pancreatic ductal adenocarcinoma is an intractable disease with frequent recurrence after resection and adjuvant therapy. The present study aimed to clarify whether artificial intelligence-assisted analysis of histopathological images can predict recurrence in patients with pancreatic ductal adenocarcinoma who underwent resection and adjuvant chemotherapy with tegafur/5-chloro-2,4-dihydroxypyridine/potassium oxonate. Eighty-nine patients were enrolled in the study. Machine-learning algorithms were applied to 10-billion-scale pixel data of whole-slide histopathological images to generate key features using multiple deep autoencoders. Areas under the curve were calculated from receiver operating characteristic curves using a support vector machine with key features alone and by combining with clinical data (age and carbohydrate antigen 19-9 and carcinoembryonic antigen levels) for predicting recurrence. Supervised learning with pathological annotations was conducted to determine the significant features for predicting recurrence. Areas under the curves obtained were 0.73 (95% confidence interval, 0.59-0.87) by the histopathological data analysis and 0.84 (95% confidence interval, 0.73-0.94) by the combinatorial analysis of histopathological data and clinical data. Supervised learning model demonstrated that poor tumor differentiation was significantly associated with recurrence. Results indicate that machine learning with the integration of artificial intelligence-driven evaluation of histopathological images and conventional clinical data provides relevant prognostic information for patients with pancreatic ductal adenocarcinoma.

ICOSLG acts as an oncogene to promote glycolysis, proliferation, migration, and invasion in gastric cancer cells

Gastric cancer (GC) has emerged as one of the most common malignancies in gastrointestinal system. Inducible T-cell costimulator ligand (ICOSLG) was found to be highly expressed in various cancers, which contributes to disease progression. This study aims to investigate the role of ICOSLG and its potential mechanism of action in dictating the aggressiveness of GC cell. ICOSLG and miR-331–3p expression patterns in cancerous and para-cancerous tissues from GC patients were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The miRNAs targeting ICOSLG were predicted by “miRDB”, “starBase,” and “TargetScan” databases. The interplay of ICOSLG and miR-331–3p in dictating the aggressiveness and glycolysis of GC cells was investigated by CCK-8 proliferation assay and Transwell migration/invasion assays, as well as the detection of glucose uptake, lactate production and ATP levels. The tumorigenesis of GC cells after ICOSLG silencing was examined in the nude mice. ICOSLG was highly expressed in GC tissues, and GC patients with high ICOSLG expression showed a poorer prognosis than the low-expression group. Further, high ICOSLG level was correlated with more advanced TNM stages, more lymph-node metastases, and poorer tumor differentiation. ICOSLG knockdown inhibited the proliferation, migration, invasion and tumor formation of GC cells, which was concomitant with reduced glucose consumption, lactate production, and ATP levels. In contrast, ICOSLG overexpression enhanced the aggressiveness of GC cells, and this effect was abrogated after the treatment with glycolysis inhibitor. We further found that miR-331–3p was a negative regulator of ICOSLG4, and miR-331–3p overexpression reduced ICOSLG4 expression and suppressed the aggressive phenotype induced by ICOSLG4 in GC cells. Together, these findings indicate that ICOSLG4, as an oncogene, is upregulated to promote glycolysis and the malignant phenotype in GC cells. miR-331–3p, which is downregulated in GC tissues, functions as a negative regulator of ICOSLG4. Targeting miR-331–3p/ICOSLG4 axis could potentially suppress GC progression.

Prognostic Effect of Preoperative Inflammatory Markers on Morbidity and Overall Survival in Pancreatic Adenocarsinoma.

His study aimed to evaluate the availability of common diagnostic tests and biochemical markers in predicting poor prognosis in patients with pancreatic adenocarcinoma (PAC). The primary outcome measure was to identify predictive prognostic factors. The secondary outcome measure was to compare predictive measures in patients who survived or did not survive in the follow-up period. Medical data of 51 patients were obtained who underwent resection surgery for PAC between January 2016 and May 2022. There were two groups according to the mortality in the follow-up period group general mortality positive (GMP; n = 29) and group general mortality negative (GMN; n = 22). Stage IIb was the most common stage in subgroups. Preoperative diagnostic tests revealed that aspartate aminotransferase (AST) level, De Ritis ratio (DRR), carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA 19-9), immature granulocyte (IG) count, and IG ratio (IG%) are higher, and hemoglobin (Hgb) levels are lower in the GMP group (P < 0.05). In univariate analysis, seven variables, including AST ≥20.5 (P = 0.001), DRR ≥1.05 (P ≤ 0.001), CEA ≥3.32 (P = 0.02), IG count ≥0.06 (P < 0.01), Hgb ≤11.75 (P = 0.01), poor differentiation (P < 0.001) and existence of life-threatening complication (P < 0.01) were identified. In multivariate analysis, only DRR (≥1.05;100% specificity and 72% sensitivity) and poor differentiation (P = 0.019) were found to be independent prognostic factors for overall survival. The median overall survival of patients with the DRR ≥1.05 and poor tumor differentiation was lower, and the mortality rate was higher than the patients with DRR and without poor tumor differentiation (10.65 ± 3.11 months vs. 61.86 ± 5.36 months and 100% vs. 26.7%, P < 0.001). Pretreatment high DRR, high IG counts and IG%, and poor differentiation of the tumor might be used as independent predictors of poor prognosis and mortality in patients with PAC.

Lymph node metastasis-related lncRNA GAS6-AS1 facilitates the progression of esophageal squamous cell carcinoma.

Lymph node metastasis is the main type of metastasis in esophageal squamous cell carcinoma (ESCC), especially when the primary tumor invasion depth reaches above the adventitia layer (T3 stage), the incidence of lymph node metastasis increases sharply. Abnormal expression of long non-coding RNAs (lncRNAs) has been confirmed in ESCC, but there are still many unknown connections between lncRNAs and lymph node metastasis. We used transcriptome sequencing (RNA-seq) to analyze 10 pairs of ESCC tissues with primary tumor stage T3 and their paired normal epithelium. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to further verify the sequencing results, and survival curve analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were used to investigate its clinical application value. We investigated the growth and metastasis effects of lncRNA GAS6-AS1 on ESCC cell lines TE-1 and KYSE410 in vitro and in vivo. Other functional experiments included cell apoptosis and cell cycle experiments. Based on our RNA-seq data, lncRNA GAS6-AS1 is highly expressed in ESCC tissues, especially in cancer tissues with lymph node metastasis. The qRT-PCR experiment analysis showed that high expression of GAS6-AS1 was related to poor tumor differentiation and tumor stage. Logistic regression analysis showed that it was an independent risk factor for lymph node metastasis, and ROC analysis validated that it could predict lymph node metastasis. Further survival analysis suggested that high expression of GAS6-AS1 was associated with patients' poor prognosis. In vitro experiments, knocking down GAS6-AS1 inhibited the growth and metastasis of ESCC cells and inhibited tumor growth in vivo. In addition, knocking down GAS6-AS1 can inhibit cell cycle and promote cell apoptosis. Our results revealed that lncRNA GAS6-AS1 obtained from RNA-seq can be used as an independent risk factor for ESCC lymph node metastasis and an effective biomarker to predict, and that it was related to the growth and metastasis of ESCC. It may represent a new biomarker to aid in the assessment of the lymph node metastasis of ESCC.