Self-folding RCA product into a parallel monolayer DNA nanoribbon and woven into a nano-fence structure by a short bridge strand.

The universal programmed construction of patterned periodic self-assembled nanostructures is a technical challenge in DNA origami nanotechnology but has numerous potential applications in biotechnology and biomedicine. In order to circumvent the dilemma that traditional DNA origami requires a long unusual single-stranded virus DNA as the scaffold and hundreds or even thousands of short strands as staples, we report a method for constructing periodically-self-folded rolling circle amplification products (RPs). The repeating unit is designed to have 3 intra-unit duplexes (inDP1,2,3) and 2 between-unit duplexes (buDP1,2). Based on the complementary pairing of bases, RPs each can self-fold into a periodic grid-patterned ribbon (GR) without the help of any auxiliary oligonucleotide staple. Moreover, by using only an oligonucleotide bridge strand, the GRs are connected together into the larger and denser planar nano-fence-shaped product (FP), which substantially reduces the number of DNA components compared with DNA origami and eliminates the obstacles in the practical application of DNA nanostructures. More interestingly, the FP-based DNA framework can be easily functionalized to offer spatial addressability for the precise positioning of nanoparticles and guest proteins with high spatial resolution, providing a new avenue for the future application of DNA assembled framework nanostructures in biology, material science, nanomedicine and computer science that often requires the ordered organization of functional moieties with nanometer-level and even molecular-level precision.

Triangle-toothed gear occlude-guided universal nanotechnology constructs 3D symmetric DNA polyhedra with high assembly efficiency for precision cancer therapy.

Chemotherapy is commonly used to treat malignant tumors. However, conventional chemotherapeutic drugs often cannot distinguish between tumor and healthy cells, resulting in adverse effects and reduced therapeutic efficacy. Therefore, zigzag-shaped gear-occlude-guided cymbal-closing (ZGC) DNA nanotechnology was developed based on the mirror-symmetry principle to efficiently construct symmetric DNA polyhedra. This nanotechnology employed simple mixing steps for efficient sequence design and assembly. A targeting aptamer was installed at a user-defined position using an octahedron as a model structure. Chemotherapeutic drug-loaded polyhedral objects were subsequently delivered into tumor cells. Furthermore, anticancer drug-loaded DNA octahedra were intravenously injected into a HeLa tumor-bearing mouse model. Assembly efficiency was almost 100 %, with no residual building blocks identified. Moreover, this nanotechnology required a few DNA oligonucleotides, even for complex polyhedrons. Symmetric DNA polyhedrons retained their structural integrity for 24 h in complex biological environments, guaranteeing prolonged circulation without drug leakage in the bloodstream and promoting efficient accumulation in tumor tissues. In addition, DNA octahedra were cleared relatively slowly from tumor tissues. Similarly, tumor growth was significantly inhibited in vivo, and a therapeutic outcome comparable to that of conventional gene-chemo combination therapy was observed. Moreover, no systemic toxicity was detected. These findings indicate the potential application of ZGC DNA nanotechnology in precision medicine.

Whole-volume histogram analysis of spectral-computed tomography iodine maps characterizes HER2 expression in gastric cancer.

BACKGROUND: Although surgery remains the primary treatment for gastric cancer (GC), the identification of effective alternative treatments for individuals for whom surgery is unsuitable holds significance. HER2 overexpression occurs in approximately 15%-20% of advanced GC cases, directly affecting treatment-related decisions. Spectral-computed tomography (sCT) enables the quantification of material compositions, and sCT iodine concentration parameters have been demonstrated to be useful for the diagnosis of GC and prediction of its invasion depth, angiogenesis, and response to systemic chemotherapy. No existing report describes the prediction of GC HER2 status through histogram analysis based on sCT iodine maps (IMs). AIM: To investigate whether whole-volume histogram analysis of sCT IMs enables the prediction of the GC HER2 status. METHODS: This study was performed with data from 101 patients with pathologically confirmed GC who underwent preoperative sCT examinations. Nineteen parameters were extracted via sCT IM histogram analysis: The minimum, maximum, mean, standard deviation, variance, coefficient of variation, skewness, kurtosis, entropy, percentiles (1st, 5th, 10th, 25th, 50th, 75th, 90th, 95th, and 99th), and lesion volume. Spearman correlations of the parameters with the HER2 status and clinicopathological parameters were assessed. Receiver operating characteristic curves were used to evaluate the parameters' diagnostic performance. RESULTS: Values for the histogram parameters of the maximum, mean, standard deviation, variance, entropy, and percentiles were significantly lower in the HER2+ group than in the HER2- group (all P < 0.05). The GC differentiation and Lauren classification correlated significantly with the HER2 status of tumor tissue (P = 0.001 and 0.023, respectively). The 99th percentile had the largest area under the curve for GC HER2 status identification (0.740), with 76.2%, sensitivity, 65.0% specificity, and 67.3% accuracy. All sCT IM histogram parameters correlated positively with the GC HER2 status (r = 0.237-0.337, P = 0.001-0.017). CONCLUSION: Whole-lesion histogram parameters derived from sCT IM analysis, and especially the 99th percentile, can serve as imaging biomarkers of HER2 overexpression in GC.

SNHG15-mediated feedback loop interplays with HNRNPA1/SLC7A11/GPX4 pathway to promote gastric cancer progression.

Dysregulation of long noncoding RNA (lncRNA) expression plays a pivotal role in the initiation and progression of gastric cancer (GC). However, the regulation of lncRNA SNHG15 in GC has not been well studied. Mechanisms for ferroptosis by SNHG15 have not been revealed. Here, we aimed to explore SNHG15-mediated biological functions and underlying molecular mechanisms in GC. The novel SNHG15 was identified by analyzing RNA-sequencing (RNA-seq) data of GC tissues from our cohort and TCGA dataset, and further validated by qRT-PCR in GC cells and tissues. Gain- and loss-of-function assays were performed to examine the role of SNHG15 on GC both in vitro and in vivo. SNHG15 was highly expressed in GC. The enhanced SNHG15 was positively correlated with malignant stage and poor prognosis in GC patients. Gain- and loss-of-function studies showed that SNHG15 was required to affect GC cell growth, migration and invasion both in vitro and in vivo. Mechanistically, the oncogenic transcription factors E2F1 and MYC could bind to the SNHG15 promoter and enhance its expression. Meanwhile, SNHG15 increased E2F1 and MYC mRNA expression by sponging miR-24-3p. Notably, SNHG15 could also enhance the stability of SLC7A11 in the cytoplasm by competitively binding HNRNPA1. In addition, SNHG15 inhibited ferroptosis through an HNRNPA1-dependent regulation of SLC7A11/GPX4 axis. Our results support a novel model in which E2F1- and MYC-activated SNHG15 regulates ferroptosis via an HNRNPA1-dependent modulation of the SLC7A11/GPX4 axis, which serves as the critical effectors in GC progression, and provides a new therapeutic direction in the treatment of GC.

Phase I trial of apatinib and paclitaxel+oxaliplatin+5-FU/levoleucovorin for treatment-naïve advanced gastric cancer.

Chinese guidelines recommend POF (paclitaxel, oxaliplatin, and 5-FU/levoleucovorin) as first-line treatment for advanced gastric cancer (AGC). Apatinib can augment the antitumor effect of paclitaxel, oxaliplatin, or fluorouracil in preclinical studies of AGC. A phase I clinical trial was conducted to evaluate the anticancer activity and maximum tolerated dose (MTD) of apatinib plus POF in treatment-naïve patients with AGC and to establish a recommended phase II dose. Participants received escalating doses of daily oral apatinib (250, 375, 500, 625, 750, and 850 mg) plus POF every 2 weeks using a conventional "3 + 3" study design. Among 21 treated patients, one experienced a dose-limiting toxicity (grade 3 skin ulceration at 850 mg). No MTD was reached. Apatinib 750 mg plus POF was recommended for phase II study. The most common grade 3-4 adverse events (AEs) were neutropenia (33.3%), mucositis (14.3%), and hand-foot syndrome (14.3%). Median progression-free and overall survival were 10.4 months (95% CI: 6.3, 14.6) and 18.4 months (95% CI: 9.8, 28.2), respectively. Apatinib up to 850 mg coadministered with POF was well tolerated with manageable AEs. The safety and anticancer activity of this regimen warrants its further investigation as first-line treatment for AGC in a larger study.

Investigating the role of LncRNA PSMG3-AS1 in gastric cancer: implications for prognosis and therapeutic intervention.

LncRNAs are widely linked to the complex development of gastric cancer, which is acknowledged worldwide as the third highest contributor to cancer-related deaths and the fifth most common form of cancer. The primary focus of this study is to examine the role of LncRNA PSMG3-AS1 in a group of individuals with gastric cancer. The results of our study indicate that PSMG3-AS1 is highly expressed in over 20 different types of cancer. Significantly, there was a clear association found between the expression of PSMG3-AS1 and a multitude of TMB and MSI tumors. PSMG3-AS1 exhibited significant upregulation in gastric cancer patients compared to healthy individuals within the gastric cancer cohort. The prognosis of gastric cancer patients is intrinsically associated with PSMG3-AS1, as confirmed by survival analysis and ROC curves. Furthermore, we created a disruption vector based on LncRNA PSMG3-AS1 and introduced it into AGS and MKN-45 cells, which are human gastric cancer cells. Significant decreases in the expression of the PSMG3-AS1 gene were noticed in both intervention groups compared to the NC group, reflecting the protein level expressions. Significantly, the proliferative and invasive capabilities of MKN-45 and AGS cells were notably reduced following transfection with PSMG3-AS1 siRNA. The results of our study indicate that disruption of the LncRNA PSMG3-AS1 gene may impact the CAV1/miR-451a signaling pathway, thereby leading to a reduction in the ability of gastric cancer cells to multiply and invade.

Deep learning radio-clinical signatures for predicting neoadjuvant chemotherapy response and prognosis from pretreatment CT images of locally advanced gastric cancer patients.

BACKGROUND: Early noninvasive screening of patients who would benefit from neoadjuvant chemotherapy (NCT) is essential for personalized treatment of locally advanced gastric cancer (LAGC). The aim of this study was to identify radio-clinical signatures from pretreatment oversampled computed tomography (CT) images to predict the response to NCT and prognosis of LAGC patients. METHODS: LAGC patients were retrospectively recruited from six hospitals from January 2008 to December 2021. An SE-ResNet50-based chemotherapy response prediction system was developed from pretreatment CT images preprocessed with an imaging oversampling method (i.e. DeepSMOTE). Then, the deep learning (DL) signature and clinic-based features were fed into the deep learning radio-clinical signature (DLCS). The predictive performance of the model was evaluated based on discrimination, calibration, and clinical usefulness. An additional model was built to predict overall survival (OS) and explore the survival benefit of the proposed DL signature and clinicopathological characteristics. RESULTS: A total of 1060 LAGC patients were recruited from six hospitals; the training cohort (TC) and internal validation cohort (IVC) patients were randomly selected from center I. An external validation cohort (EVC) of 265 patients from five other centers was also included. The DLCS exhibited excellent performance in predicting the response to NCT in the IVC [area under the curve (AUC), 0.86] and EVC (AUC, 0.82), with good calibration in all cohorts ( P >0.05). Moreover, the DLCS model outperformed the clinical model ( P <0.05). Additionally, we found that the DL signature could serve as an independent factor for prognosis [hazard ratio (HR), 0.828, P =0.004]. The concordance index (C-index), integrated area under the time-dependent ROC curve (iAUC), and integrated Brier score (IBS) for the OS model were 0.64, 1.24, and 0.71 in the test set. CONCLUSION: The authors proposed a DLCS model that combined imaging features with clinical risk factors to accurately predict tumor response and identify the risk of OS in LAGC patients prior to NCT, which can then be used to guide personalized treatment plans with the help of computerized tumor-level characterization.

Examined lymph node count for gastric cancer patients after curative surgery.

Lymph node (LN) metastasis is the most common form of metastasis in gastric cancer (GC). The status and stage of LN metastasis are important indicators that reflect the progress of GC. The number of LN metastases is still the most effective index to evaluate the prognosis of patients in all stages of LN metastasis. Examined LN (ELN) count refers to the number of LNs harvested from specimens by curative gastrectomy for pathological examination. This review summarizes the factors that influence ELN count, including individual and tumor factors, intraoperative dissection factors, postoperative sorting factors, and pathological examination factors. Different ELN counts will lead to prognosis-related stage migration. Fine LN sorting and regional LN sorting are the two most important LN sorting technologies. The most direct and effective way to harvest a large number of LNs is for surgeons to perform in vitro fine LN sorting.

Development and validation of prognostic model based on extragastric lymph nodes metastasis and lymph node ratio in node-positive gastric cancer: a retrospective cohort study based on a multicenter database.

BACKGROUND: Regional lymph node metastasis (LNM) is a competent and the most intensive predictor for the prognostic evaluation of patients after curative surgery. This study is based on the databases of two large medical centers in North and South China. It aims to establish a prognostic model based on extragastric LNM (ELNM) and lymph node ratio (LNR) in node-positive gastric cancer (GC). METHODS: Clinical data of 874 GC patients with pathologically confirmed LNM in a large medical center in southern China, were included as the training cohort. In addition, the clinical data of 674 patients with pathologically confirmed LNM from a large medical center in northern China were used as the validation cohort. RESULTS: In the training cohort, a modified N staging system (mNstage) based on ELNM and LNR was established; it has a significantly higher prognostic accuracy than the pN, LNR and ELNM staging system (Akaike Information Criterion, pN stage vs. LNR stage vs. ELNM stage vs. mN stage=5498.479 vs. 5537.815 vs. 5569.844 vs. 5492.123; Bayesian Information Criterion, pN stage vs. LNR stage vs. ELNM stage vs. mN stage=5512.799 vs. 5547.361 vs. 5574.617 vs. 5506.896; likelihood-ratio χ2 , pN stage vs. LNR stage vs. ELNM stage vs. mN stage=177.7 vs. 149.8 vs. 115.79 vs. 183.5). In the external validation, mNstage also has higher prognostic accuracy than the pN, LNR and ELNM staging system. Cox multivariate regression analysis showed that age, mNstage, pT stage, and perineural invasion were independent factors. A nomogram model was established according to the four factors (age, mNstage, pT stage, and perineural invasion). The nomogram model was greater than the traditional tumor-node-metastasis (TNM) staging in the training cohort [1-year area under the curve (AUC), American Joint Commission for Cancer (AJCC) 8th TNM vs. nomogram=0.692 vs. 0.746, 3-year AUC: AJCC 8th TNM vs. nomogram=0.684 vs. 0.758, 5-year AUC: AJCC 8th TNM vs. nomogram=0.725 vs. 0.762]. In the external validation, the nomogram also showed better prognostic value and greater prediction accuracy than the traditional TNM staging. CONCLUSION: The prognostic model based on ELNM and LNR has good prognostic prediction in patients with node-positive GC.

DeAF: A multimodal deep learning framework for disease prediction.

Multimodal deep learning models have been applied for disease prediction tasks, but difficulties exist in training due to the conflict between sub-models and fusion modules. To alleviate this issue, we propose a framework for decoupling feature alignment and fusion (DeAF), which separates the multimodal model training into two stages. In the first stage, unsupervised representation learning is conducted, and the modality adaptation (MA) module is used to align the features from various modalities. In the second stage, the self-attention fusion (SAF) module combines the medical image features and clinical data using supervised learning. Moreover, we apply the DeAF framework to predict the postoperative efficacy of CRS for colorectal cancer and whether the MCI patients change to Alzheimer's disease. The DeAF framework achieves a significant improvement in comparison to the previous methods. Furthermore, extensive ablation experiments are conducted to demonstrate the rationality and effectiveness of our framework. In conclusion, our framework enhances the interaction between the local medical image features and clinical data, and derive more discriminative multimodal features for disease prediction. The framework implementation is available at https://github.com/cchencan/DeAF.

The Influence of Group No.8p Lymph Node Dissection on the Prognosis of Advanced Gastric Cancer.

BACKGROUND: Controversy over whether No.8p lymph nodes (LNs) involvement is distant or regional metastasis remains, and the possible inclusion of No.8p LNs in D2 lymphadenectomy is unclear. AIM: This work aimed to investigate the effect of No.8p LN dissection on the prognosis of patients with different LN metastases in advanced gastric cancer (GC). METHODS: A retrospective case-control study was used to collect 1149 cases of radical gastrectomy from July 2003 to April 2013. The patients were divided into the No.8a group (303 cases) and the No.8a + 8p group (846 cases) according to whether No.8p LN dissection was performed. The effect of No.8p LN dissection on the prognosis of patients with different total number of LN metastasis was analyzed. RESULTS: Both No.8p positive and No.8p dissection were independent prognostic factors in patients with advanced GC. The 5-year overall survival rate (OS) of the positive No.8p group was 13.0%, and that of the negative No.8p group was 66.6%; the difference was significant (P < 0.05). In the group where the total number of LN metastasis was 3-15, the OS of patients with positive No.8p was significantly lower than that of the negative group (P < 0.05). The 5-year OS of the No.8a + 8p dissection group was 65.4%, and that of the No.8a dissection group was 55.5%; the difference was significant (P < 0.05). In the group where the total number of LN metastasis was 0-2, the No.8a + 8p dissection group had significantly higher OS than the No.8a dissection group (P < 0.05). CONCLUSION: For patients with advanced GC, No.8p LN metastasis indicates a poor prognosis. LN dissection in the No.8a + 8p group may further improve the prognosis of some patients, especially when the total number of LN metastasis is 0-2.

Development of a tongue image-based machine learning tool for the diagnosis of gastric cancer: a prospective multicentre clinical cohort study.

Background: Tongue images (the colour, size and shape of the tongue and the colour, thickness and moisture content of the tongue coating), reflecting the health state of the whole body according to the theory of traditional Chinese medicine (TCM), have been widely used in China for thousands of years. Herein, we investigated the value of tongue images and the tongue coating microbiome in the diagnosis of gastric cancer (GC). Methods: From May 2020 to January 2021, we simultaneously collected tongue images and tongue coating samples from 328 patients with GC (all newly diagnosed with GC) and 304 non-gastric cancer (NGC) participants in China, and 16 S rDNA was used to characterize the microbiome of the tongue coating samples. Then, artificial intelligence (AI) deep learning models were established to evaluate the value of tongue images and the tongue coating microbiome in the diagnosis of GC. Considering that tongue imaging is more convenient and economical as a diagnostic tool, we further conducted a prospective multicentre clinical study from May 2020 to March 2022 in China and recruited 937 patients with GC and 1911 participants with NGC from 10 centres across China to further evaluate the role of tongue images in the diagnosis of GC. Moreover, we verified this approach in another independent external validation cohort that included 294 patients with GC and 521 participants with NGC from 7 centres. This study is registered at ClinicalTrials.gov, NCT01090362. Findings: For the first time, we found that both tongue images and the tongue coating microbiome can be used as tools for the diagnosis of GC, and the area under the curve (AUC) value of the tongue image-based diagnostic model was 0.89. The AUC values of the tongue coating microbiome-based model reached 0.94 using genus data and 0.95 using species data. The results of the prospective multicentre clinical study showed that the AUC values of the three tongue image-based models for GCs reached 0.88-0.92 in the internal verification and 0.83-0.88 in the independent external verification, which were significantly superior to the combination of eight blood biomarkers. Interpretation: Our results suggest that tongue images can be used as a stable method for GC diagnosis and are significantly superior to conventional blood biomarkers. The three kinds of tongue image-based AI deep learning diagnostic models that we developed can be used to adequately distinguish patients with GC from participants with NGC, even early GC and precancerous lesions, such as atrophic gastritis (AG). Funding: The National Key R&D Program of China (2021YFA0910100), Program of Zhejiang Provincial TCM Sci-tech Plan (2018ZY006), Medical Science and Technology Project of Zhejiang Province (2022KY114, WKJ-ZJ-2104), Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer (JBZX-202006), Natural Science Foundation of Zhejiang Province (HDMY22H160008), Science and Technology Projects of Zhejiang Province (2019C03049), National Natural Science Foundation of China (82074245, 81973634, 82204828), and Chinese Postdoctoral Science Foundation (2022M713203).

Incidence and clinical characteristics of hypertriglyceridemic acute pancreatitis: A retrospective single-center study.

BACKGROUND: The incidence of hypertriglyceridemic acute pancreatitis (HTG-AP) has increased yearly, but updated population-based estimates on the incidence of HTG-AP are lacking. Reducing serum triglyceride (TG) levels quickly is crucial in the early treatment of HTG-AP. Decreased serum TG levels are treated by non-invasive methods, which include anti-lipidemic agents, heparin, low-molecular weight heparin, and insulin, and invasive methods, such as blood purification including hemoperfusion (HP), plasmapheresis, and continuous renal replacement therapy. However, authoritative guidelines have not been established. Early selection of appropriate treatment is important and beneficial in controlling the development of HTG-AP. AIM: To evaluate the effect between patients treated with intravenous insulin (INS) and HP to guide clinical treatment. METHODS: We retrospectively reviewed 371 patients with HTG-AP enrolled in the Department of Fujian Provincial Hospital form April 2012 to March 2021. The inpatient medical and radiologic records were reviewed to determine clinical features, severity, complications, mortality, recurrence rate, and treatment. Multivariate logistic regression analyses were used to analyze risk factors for severe HTG-AP. Propensity score matching was used to compare the clinical outcomes of INS and HP. RESULTS: A total of 371 patients met the HTG-AP criteria. The incidence of HTG-AP was increased by approximately 2.6 times during the 10 years (8.4% in April 2012-March 2013 and 22.3% in April 2020-March 2021). The highest incidence rate of acute pancreatitis was observed for men in the age group of 30-39 years. The amylase level was elevated in 80.1% of patients but was only three times the normal value in 46.9% of patients. The frequency of severe acute pancreatitis (26.9%), organ failure (31.5%), rate of recurrence (32.9%), and mortality (3.0%) of HTG-AP was high. Improved Marshall score, modified computed tomography severity index score, baseline TG, baseline amylase, C-reactive protein (CRP), albumin, aspartate aminotransferase, low-density lipoprotein cholesterol, urea nitrogen, creatinine, calcium, hemoglobin, free triiodothyronine, admission to intensive care unit, and mortality were significantly different between patients with different grades of severity (P < 0.050). Multivariate logistic regression analysis confirmed that high CRP [P = 0.005, odds ratio (OR) = 1.011, 95%CI: 1.003-1.019], low calcium (P = 0.003, OR = 0.016, 95%CI: 0.001-0.239), and low albumin (P = 0.023, OR = 0.821, 95%CI: 0.693-0.973) were risk factors of severe HTG-AP. After propensity score matching adjusted by sex, age, severity of HTG-AP, and baseline TG, the serum TG significantly decreased in patients treated with INS (P < 0.000) and HP (P < 0.000) within 48 h. However, the clearance rate of TG (57.24 ± 33.70% vs 56.38 ± 33.61%, P = 0.927) and length of stay (13.04 ± 7.92 d vs 12.35 ± 6.40 d, P = 0.730) did not differ between the two groups. CONCLUSION: The incidence of HTG-AP exhibited a significant increase, remarkable severity, and recurrent trend. Patients with mild and moderately severe acute pancreatitis can be treated effectively with INS safely and effectively without HP.

High Expression of FCRLB Predicts Poor Prognosis in Patients With Colorectal Cancer.

Background: Mining the prognostic biomarkers of colorectal cancer (CRC) has important clinical and scientific significance. The role of Fc receptor-like B (FCRLB) in solid tumors has never been reported or studied to our knowledge, and the prognostic role of FCRLB in CRC still awaits characterization. Methods: The potential prognostic factor FCRLB was screened out through TCGA database analysis. Then, its expression and associations with clinicopathological variables were assessed in the TCGA CRC cohort. The prognostic value of FCRLB was examined with multiple methods, such as the Kaplan-Meier method, ROC curve, time-dependent ROC analysis, and prediction model nomograms. Then, functional enrichment and annotation among the high and low FCRLB groups were achieved utilizing GO and KEGG analyses and GSEA. Fresh CRC tissue samples obtained clinically were used for the preparation of the tissue microarray and for further validation. Results: FCRLB was highly expressed in CRC tissues compared to normal tissues. Moreover, over-expression of FCRLB correlated with higher CEA levels, advanced T stage, N stage, M stage, AJCC stage, lymphatic invasion, perineural invasion, and incomplete resection (R1 and R2 resection). In addition, high expression of FCRLB was closely correlated to less favorable OS, DSS, and PFI. The analysis of CRC tissue microarray further confirmed the conclusion drawn from the TCGA data analysis. Conclusion: FCRLB is notably up-regulated in CRC tissues and may serve as a potential biomarker of CRC.

Corrigendum: Bioinformatics Analysis Reveals an Association Between Cancer Cell Stemness, Gene Mutations, and the Immune Microenvironment in Stomach Adenocarcinoma.

[This corrects the article DOI: 10.3389/fgene.2020.595477.].

Lobaplatin hyperthermic intraperitoneal chemotherapy plus cytoreduction and rechallenge using cetuximab for wild-type RAS peritoneal metastatic colon cancer: a case report and literature review.

BACKGROUND: Synchronous peritoneal metastasis of colorectal cancer usually predicts a bleak prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) have brought a glimmer of hope to the treatment of peritoneal cancer. Few cases treated with lobaplatin have been reported in the literature and the regimen is controversial. In this case, the comprehensive treatment scheme of lobaplatin-based HIPEC plus CRS and rechallenge using cetuximab plus systemic chemotherapy is effective, especially for the patients with left colon cancer (wild-type RAS). CASE PRESENTATION: A 49 year-old man with signet ring cell carcinoma of sigmoid colon with extensive abdominal metastasis (wild-type RAS) was hospitalized with prolonged abdominal pain, distention and abdominal mass. After receiving HIPEC with lobaplatin and XELOX regimen combined with cetuximab for eight cycles, the patient had been treated with the FOLFIRI regimen and cetuximab for 24 cycles, which discontinued due to myelosuppression. Because the disease recurred unfortunately 4 months later, the FOLFIRI + cetuximab regimen was initiated again and stopped after two cycles. Intestinal obstruction occurred 1 month later, so open total colectomy, CRS + HIPEC and ileorectal anastomosis were performed. Capecitabine adjuvant chemotherapy was administered, followed by the maintenance therapy with FOLFIRI + cetuximab regimen. After that, the patient has been in relatively stable condition. By August 2021, the overall survival is more than 45 months, which displays significant curative effect. CONCLUSION: For peritoneal metastasis from left colon cancer, the management with CRS + lobaplatin HIPEC and rechallenge of systemic chemotherapy plus targeted medicine based on gene detection can dramatically improve prognosis and extend the overall survival.

Laparoscopic Versus Open Total Gastrectomy for Advanced Gastric Cancer: A Multicenter, Propensity Score-Matched Cohort Study in China.

BACKGROUND: Given the great technical difficulty and procedural complexity of laparoscopic total gastrectomy (LTG), the technical and oncologic safety of LTG versus open total gastrectomy (OTG) in the field of advanced gastric cancer (AGC) is yet undetermined. OBJECTIVE: This multicenter cohort study aimed to compare the surgical and oncological outcomes of LTG with those of OTG in AGC patients. PATIENTS AND METHODS: In total, 588 patients from 3 centers who underwent primary total gastrectomy with D2 lymphadenectomy, by well-trained surgeons with adequate experience, for pathologically confirmed locally AGC (T2N0-3, T3N0-3, or T4N0-3) between January 1, 2011, and December 31, 2015, were identified, and their clinical data were collected from three participating centers. After 1:1 propensity score matching (PSM), 450 cases (LTG, n = 225; OTG, n = 225) were eligible and assessed. RESULTS: No significant difference in the number of retrieved lymph nodes, 5-year disease-free survival (DFS) rates, or 5-year overall survival (OS) rates between both surgical groups were observed. Although LTG had significantly longer surgical time (262 vs. 180 min, p < 0.001), LTG was associated with fewer postoperative complications [relative risk (RR) 0.583, 95% CI 0.353-0.960, p = 0.047), less intraoperative bleeding (120 vs. 200 ml, p < 0.001), longer proximal margin resection (3 vs. 2 cm, p < 0.001), and shorter postoperative hospitalization (11 vs. 13 days, p < 0.001). The mortality rate was comparable in both groups. CONCLUSIONS: LTG was not inferior to OTG in terms of survival outcomes and was associated with shorter surgical and postoperative hospitalization time and fewer postoperative complications, suggesting LTG with D2 lymphadenectomy as an important alternative to OTG for patients with AGC, but to be carried out in highly experienced centers.

Prognostic value of preoperative body mass index for diabetic patients with non-metastasis gastric cancer: a single center experience.

AIM: This study was designed to investigate the prognostic effect of preoperative body mass index (BMI) for Type 2 diabetes mellitus (T2DM) patients with non-metastasis gastric cancer (GC) who underwent D2 gastrectomy. METHODS: T2DM patients with pT1-4bN0-3bM0 GC were retrospectively collected in Department of Gastrointestinal Surgical Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital from January, 2000 to December, 2010. These patients underwent D2 radical resection of the stomach combined with regional lymphadenectomy. Chi-square test was used to analyze unordered categorical variables and ranked data, followed by Kaplan-Meier analysis as well as Cox regression models to detect risk factors for survival outcomes. In addition, the cut-off point was determined by the X-tile program. All analyses were carried out using survival package of R and SPSS Software. RESULTS: A total of 302 T2DM patients with pT1-4bN0-3bM0 GC were collected and analyzed. The cut-off points of BMI, identified by the X-tile program, was 19 kg/m2. Patients with low BMI (< 19 kg/m2) had a higher percentage of advanced T stage (T4a and T4b), more advanced TNM stage (stage IIIA, IIIB and IIIC), and more elevated level of serum carcinoembryonic antigen (CEA), compared to those with high BMI (> 19 kg/m2) (all P < 0.05). In the low BMI subgroup, the 5-year overall survival rate was 39.02%, which was as high as 58.11% in the high BMI subgroup (P < 0.05). In the multivariate Cox regression model revealed that IIIC stage (OR = 3.101), N3b stage (OR = 3.113) were the most important prognostic indicators, followed by pretreatment BMI (OR = 2.136). CONCLUSION: Low preoperative BMI (< 19 kg/m2) was a poor prognostic marker for T2DM patients with pT1-4bN0-3bM0 GC.

A 13-Gene Metabolic Prognostic Signature Is Associated With Clinical and Immune Features in Stomach Adenocarcinoma.

Patients with advanced stomach adenocarcinoma (STAD) commonly show high mortality and poor prognosis. Increasing evidence has suggested that basic metabolic changes may promote the growth and aggressiveness of STAD; therefore, identification of metabolic prognostic signatures in STAD would be meaningful. An integrative analysis was performed with 407 samples from The Cancer Genome Atlas (TCGA) and 433 samples from Gene Expression Omnibus (GEO) to develop a metabolic prognostic signature associated with clinical and immune features in STAD using Cox regression analysis and least absolute shrinkage and selection operator (LASSO). The different proportions of immune cells and differentially expressed immune-related genes (DEIRGs) between high- and low-risk score groups based on the metabolic prognostic signature were evaluated to describe the association of cancer metabolism and immune response in STAD. A total of 883 metabolism-related genes in both TCGA and GEO databases were analyzed to obtain 184 differentially expressed metabolism-related genes (DEMRGs) between tumor and normal tissues. A 13-gene metabolic signature (GSTA2, POLD3, GLA, GGT5, DCK, CKMT2, ASAH1, OPLAH, ME1, ACYP1, NNMT, POLR1A, and RDH12) was constructed for prognostic prediction of STAD. Sixteen survival-related DEMRGs were significantly related to the overall survival of STAD and the immune landscape in the tumor microenvironment. Univariate and multiple Cox regression analyses and the nomogram proved that a metabolism-based prognostic risk score (MPRS) could be an independent risk factor. More importantly, the results were mutually verified using TCGA and GEO data. This study provided a metabolism-related gene signature for prognostic prediction of STAD and explored the association between metabolism and the immune microenvironment for future research, thereby furthering the understanding of the crosstalk between different molecular mechanisms in human STAD. Some prognosis-related metabolic pathways have been revealed, and the survival of STAD patients could be predicted by a risk model based on these pathways, which could serve as prognostic markers in clinical practice.

Short-term survival and safety of apatinib combined with oxaliplatin and S-1 in the conversion therapy of unresectable gastric cancer.

BACKGROUND: We conducted a single-arm phase II trial to investigate the short-term efficacy and safety of apatinib combined with oxaliplatin and S-1 in the treatment of unresectable gastric cancer. PATIENTS AND METHODS: Previously untreated patients with unresectable HER-2-negative advanced gastric cancer were selected. All the patients received six cycles of S-1 and oxaliplatin and five cycles of apatinib, which were administered at intervals of three weeks. The surgery was performed after six cycles of drug treatment. The primary endpoints were radical resection (R0) rate and safety. This study was registered with the China Trial Register, number ChiCTR-ONC-17010430  (01/12/2016-01/12/2022). RESULTS: A total of 39 patients were enrolled. Efficacy evaluation was feasible for 37 patients. One patient achieved complete response (CR, 2.7%), 26 patients achieved partial response (PR, 70.3%), three patients had stable disease (SD, 8.1%) and seven patients had progressive disease (PD, 18.9%). The objective response rate (ORR) was 73.0% and the disease control rate (DCR) was 81.1%. 22 patients underwent surgery, among which 14 patients underwent radical resection (R0), with a R0 resection rate of 63.6%. The 1-year survival rate of the surgical group (22 patients) was 71.1% and the 2-year survival rate was 41.1%. The median survival time was 21 months. The incidence of adverse events (AEs) was 100%. Leucopenia (65.3%) and granulocytopenia (69.2%) were the most common hematological AEs. The most common non-hematological AEs were fatigue (51.3%) and oral mucositis (35.9%). CONCLUSION: Apatinib combined with oxaliplatin and S-1 showed good short-term survival and acceptable safety in the conversion therapy of unresectable gastric cancer.