Machine learning to establish three sphingolipid metabolism genes signature to characterize the immune landscape and prognosis of patients with gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors worldwide. Nevertheless, GC still lacks effective diagnosed and monitoring method and treating targets. This study used multi omics data to explore novel biomarkers and immune therapy targets around sphingolipids metabolism genes (SMGs). METHOD: LASSO regression analysis was performed to filter prognostic and differently expression SMGs among TCGA and GTEx data. Risk score model and Kaplan-Meier were built to validate the prognostic SMG signature and prognostic nomogram was further constructed. The biological functions of SMG signature were annotated via multi omics. The heterogeneity landscape of immune microenvironment in GC was explored. qRT-PCR was performed to validate the expression level of SMG signature. Competing endogenous RNA regulatory network was established to explore the molecular regulatory mechanisms. RESULT: 3-SMGs prognostic signature (GLA, LAMC1, TRAF2) and related nomogram were constructed combing several clinical characterizes. The expression difference and diagnostic value were validated by PCR data. Multi omics data reveals 3-SMG signature affects cell cycle and death via several signaling pathways to regulate GC progression. Overexpression of 3-SMG signature influenced various immune cell infiltration in GC microenvironment. RBP-SMGs-miRNA-mRNAs/lncRNAs regulatory network was built to annotate regulatory system. CONCLUSION: Upregulated 3-SMGs signature are excellent predictive diagnosed and prognostic biomarkers, providing a new perspective for future GC immunotherapy.

Antibiotic resistance in Helicobacter pylori: From potential biomolecular mechanisms to clinical practice.

Increasing rates of Helicobacter pylori resistance are associated with multiple clinical challenges. Bacterial factors linked to H. pylori resistance are mutations, efflux pumps, and biofilms. Gene mutations such as nucleic acid synthesis-related gene mutations, rRNA coding gene mutations, and cell wall synthesis-related gene mutations are the most important mechanisms by which H. pylori evades bactericidal effects. These mechanisms are also closely related to the biological activity of the efflux pump systems and biofilms. Activation of the efflux pump system and biofilm formation both lead to the emergence of MDR strains, further increasing the difficulty of eradication therapy. In this review, the status of antibiotic resistance in H. pylori from different regions and countries is summarized and compared, and H. pylori resistance profiles and their changing trends in the clinic are described. Then, research progress on biomolecular mechanisms underlying antibiotic resistance, diagnostic methods, and treatment strategies are introduced and discussed. Challenges resulting from increasing resistance, potential solutions to combat increasing resistance, and future directions are discussed to help clinicians and researchers better address the emergence and spread of resistant H. pylori strains and optimize drug regimens. With the rate of H. pylori resistance to commonly used antibiotics increasing, more attention should be given to the selection of antibiotics and to monitoring resistance when antibiotics are used for clinical eradication treatment. Individualized precise eradication treatment under the guidance of drug susceptibility testing will become the mainstream method of treatment in the future.

Antibiotic resistance status of helicobacter pylori strains isolated from initial eradication patients in Ningbo, China, from 2017 to 2021.

BACKGROUND: Resistance of Helicobacter pylori (H. pylori) to antibiotics is an evolving and dynamic process. Presence of antibiotic resistance impacts the success rate of initial eradication strategies in the clinic. AIM: To improve the success rate of initial eradication therapy and explore new antibiotic regimens, a large sample-based study utilizing antimicrobial susceptibility testing was performed. A total of 2508 H. pylori strains from patients subjected to initial eradication therapy were isolated, cultured, and tested for drug susceptibility from 2017 to 2021. The minimal inhibitory concentration (MIC) was recorded. H. pylori susceptibility profiles and its change trends from initial eradication patients were analyzed. The relationships between drug resistance, year of sample collection, age, and sex of patients were analyzed. RESULTS: The overall resistance rates were as follows: amoxicillin (9.25%), clarithromycin (38.48%), levofloxacin (42.86%), furazolidone (11.28%), doxycycline (8.56%), rifampicin (10.81%), tinidazole (74.32%), gatifloxacin (61.71%), tetracycline (0%), metronidazole (78.71%), ornidazole (97.87%), and fosfomycin (31.67%). Only 38.04% of the strains were pansusceptible to amoxicillin, clarithromycin, levofloxacin, and furazolidone, followed by those of mono resistance (29.90%), double resistance (24.96%), triple resistance (6.34%), and quadruple resistance (0.76%). Significant differences in the resistance rate and MIC were also observed in different age and sex groups. Time of collection and patient age and sex were associated with the distribution of antibiotic resistance. CONCLUSION: With the increasing resistance rate and multiple resistance of H. pylori to commonly used antibiotics, drug susceptibility testing is imperative to permit individualized therapy, and a regimen containing the combination of amoxicillin, furazolidone, tetracycline, doxycycline, or rifampicin is reasonable for initial empirical eradication therapy.

Hsa_circ_0001020 Serves as a Potential Biomarker for Gastric Cancer Screening and Prognosis.

Circular RNAs (circRNAs) are an intriguing class of RNAs with covalently closed-loop structures. With characteristics of high stability and disease-specific expression, circRNAs are emerging as ideal targets for cancer therapy. However, the screening utility and clinical value of circRNAs in gastric cancer (GC) remain largely elusive. We detected levels of hsa_circ_0001020 in cell lines and tissue and plasma samples and investigated its clinicopathological correlations. Kaplan-Meier survival curves and regression analyses were used to analyze its prognostic value. Receiver operating characteristic curves and biomarker combinations were examined to verify its screening value. Bioinformatics analysis was also performed to predict potential biological functions. Our tests found that hsa_circ_0001020 was significantly upregulated in GC cell lines, GC tissue samples, and even in plasma. High hsa_circ_0001020 expression levels in GC tissues were significantly associated with distal metastasis and blood carbohydrate antigen 19-9 (CA19-9). GC patients with high hsa_circ_0001020 had a lower overall survival and disease-free survival time than the low levels. Regression analysis suggested that the level of hsa_circ_0001020 expression was an independent prognostic factor for survival time. As a biomarker for GC, hsa_circ_0001020 showed a superior AUC, sensitivity, and specificity than carcinoembryonic antigen and CA19-9, and was suitable for combination with clinical tumor biomarkers. Bioinformatics analysis provided valuable clues for the possible oncogenic pathways of GC, such as the FoxO and p53 signaling pathways. In conclusion, our study found that hsa_circ_0001020 in GC could be a reliable biomarker to screen for GC and predict prognosis.

High expression of the ferroptosis-associated MGST1 gene in relation to poor outcome and maladjusted immune cell infiltration in uterine corpus endometrial carcinoma.

BACKGROUND: Uterine corpus endometrial carcinoma (UCEC) tightly correlates with dysregulated iron homeostasis. MGST1 (microsomal glutathione S-transferase 1) involves in the regulation of oxidative stress and plays a key role in inhibiting iron-mediated cell death in cancer cells. Hence, we aimed to illuminate the characteristics of MGST1 expression and prognosis in UCEC using bioinformatics prediction to provide novel perspectives for theoretical supplementation and ferroptosis-based immunotherapy. METHODS: We retrieved MGST1 expression data via several public data portals. The relationships between MGST1 expression and clinicopathologic characteristics as well as survival time were evaluated via multivariate methods and Kaplan-Meier survival curves. The MGST1-interacting protein-protein interaction was also established by the STRING website. The TIMER and GEPIA databases were used to illustrate the association between MGST1 expression and infiltrated immune cells. We used the MethSurv website and the UALCAN website to determine the relationship between MGST1 expression and DNA methylation. RESULTS: MGST1 overexpression in UCEC compared with normal tissues correlates with different histological types, a lack of hormone therapy and poor survival time. MGST1 interacts with several ferroptosis-related proteins. Overexpression of MGST1 was accompanied by lower levels of NK cell and CD8+ T cell infiltration, higher myeloid-derived suppressor cell infiltration and different immunocytes with corresponding markers. Hypermethylation and low promoter methylation cooperate to regulate MGST1 expression. CONCLUSION: Elevated MGST1 expression is related to tumour development and poor prognosis, as well as dysregulated infiltration of immune cells in UCEC, which can be a potential prognostic indicator and ferroptosis-based immunotherapy target.

Biological and clinical implications of hsa_circ_0086720 in gastric cancer and its clinical application.

BACKGROUND: Circular RNAs (circRNAs) are thought to be vital participants in carcinogenesis and have the characteristics of being stable, specific, and well conserved. However, their clinical significance and application value in gastric cancer (GC) are still poorly understood. Hsa_circ_0086720 was found to be a dysregulated circRNA in GC by microarray screening and was further explored for its clinical significance and application. METHODS: Hsa_circ_0086720 was detected in GC cell lines, tissues, and plasma, and the clinicopathological correlations were investigated. The existence, stability, origin, and change in the plasma hsa_circ_0086720 level were verified in early GC patients. Moreover, receiver operating characteristic and Kaplan-Meier survival curves were constructed to analyze the diagnostic and prognostic values, and bioinformatics analysis was used to identify the potential functions. Finally, risk factors and nomogram predicting were established. RESULTS: Hsa_circ_0086720 was found to be downregulated in gastric carcinogenesis, and tissue hsa_circ_0086720 was negatively associated with perineural invasion, Borrmann type, disease-free survival, and overall survival. Hsa_circ_0086720 was stable in circulating plasma and was actively secreted by cells in gastric carcinogenesis. As a biomarker for early GC screening, plasma hsa_circ_0086720 had good sensitivity and specificity, and its stability met the clinical application requirements. Bioinformatics analysis suggested that dysregulated hsa_circ_0086720 has important functions in gastric carcinogenesis. Univariate Cox regression analysis identified factors associated with overall survival time and disease-free survival time. The nomograms showed good accuracy of predicting survival time. CONCLUSION: Hsa_circ_0086720 is a novel biomarker for screening early GC and predicting the prognosis of advanced-stage patients.

[Effect of Circular RNA hsa_circ_0067582 on the Proliferation and Invasion Ability of Gastric Cancer Cells].

Objective To investigate the effects on cell proliferation and invasion of the circular RNA hsa_circ_0067582 in gastric cancer(GC). Methods After hsa_circ_0067582 overexpression (Oe-circ_0067582) plasmid was transfected into AGS and SGC-7901 cells,the cell viability,proliferation,invasion ability,and apoptosis were detected by CCK-8,colony formation and EdU assays,Transwell assay,and flow cytometry,respectively.Western blotting was employed to detect the expression levels of proteins related to the cell apoptosis and epithelial-mesenchymal transition(EMT).The effect of Oe-circ_0067582 on the growth of SGC-7901 cells in nude mice was observed.Bioinformatics tools were used to predict the binding target miRNA of hsa_circ_0067582,and the competing endogenous RNA(ceRNA)regulatory network was established.Finally,functional enrichment was performed to analyze the biological functions of the target genes of the predicted miRNA. Results Compared with the pLO-ciR(empty plasmid)group,the Oe-circ_0067582 group in AGS and SGC-7901 cells attenuated the cell viability(t=7.883,P=0.001;t=5.679,P=0.005),proliferation(t=6.709,P=0.003;t=5.857,P=0.003),and invasion ability(t=7.782,P=0.002;t=6.342,P=0.003)and induced cell apoptosis(t=7.225,P=0.002;t=11.509,P=0.001).Western blotting showed that the Oe-circ_0067582 group in AGS and SGC-7901 cells up-regulated the protein levels of cysteinyl aspartate specific proteinase (Caspase) 3(t=6.863,P=0.002;t=7.024,P=0.001),Caspase 7(t=3.295,P=0.04;t=6.008,P=0.004),Caspase 9(t=4.408,P=0.012;t=6.278,P=0.004),and E-cadherin(t=12.453,P=0.002;t=10.867,P=0.001),while down-regulated those of Vimentin(t=7.242,P=0.002;t=5.694,P=0.004)and N-cadherin(t=6.480,P=0.003;t=7.446,P=0.001).Furthermore,Oe-circ_0067582 significantly inhibited the growth of tumor in the SGC-7901 tumor-bearing nude mice(t=3.526,P=0.017).The prediction based on TargetScan and miRnada suggested that hsa_circ_0067582 can competitively bind to hsa-miR-181b-3p,hsa-miR-337-3p,hsa-miR-421,and hsa-miR-548d-3p.The functional enrichment indicated that the target genes of miRNA were involved in multiple cancer-related biological processes including negative regulation of apoptotic process,gene expression,transcriptional misregulation in cancer,transforming growth factor-ß,and p53 signaling pathways. Conclusion Oe-circ_0067582 can inhibit the proliferation and attenuate EMT process to reduce the invasion ability of AGS and SGC-7901 cells,which provides a new target for the treatment of GC.

Circular RNA MTO1 suppresses tumorigenesis of gastric carcinoma by sponging miR-3200-5p and targeting PEBP1.

Gastric carcinoma (GC) is one of the most common cancers with the fifth highest incidence of malignant tumors and the second highest death rate in the world. Ever-increasing investigations have shown that circular RNAs (circRNAs) are involved in the development of numerous cancers. But so far, the recognization for circMTO1 that is realized and studied as a cancer-suppressing gene is a small part and the regulatory mechanism of circMTO1 in GC has yet to be further explored. In this study, our experimental results delineated that circMTO1 exhibited much lower expression level in GC tissues and cells. CircMTO1 overexpression slowed down GC progression via inhibiting cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process. Besides, circMTO1 acted as a sponge for miR-3200-5p as well as it could negatively regulate the expression of miR-3200-5p. Moreover, circMTO1 was verified to compete with PEBP1 to bind to miR-3200-5p, thus decelerating the development of GC. In a word, this study was the first to indagate the underlying mechanism of circMTO1 in GC and confirmed circMTO1 exerted its anti-cancer effects by miR-3200-5p/PEBP1 axis, implying that circMTO1 may become a new promising therapeutic target for GC patients.

Clinical significances of hsa_circ_0067582 and hsa_circ_0005758 in gastric cancer tissues.

BACKGROUND: Circular RNAs (circRNAs) are a special class of endogenous noncoding RNAs that have numerous biological functions in normal situation and diseases including cancers. However, the clinical significance of circRNAs in gastric cancer (GC) remains largely unknown. Here, we chose two representative circRNAs, hsa_circ_0067582 and hsa_circ_0005758, to investigate their clinical significance in GC patients. METHODS: Using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), we explored the expression levels of hsa_circ_0067582 and hsa_circ_0005758 in tissues with different stages of gastric tumorigenesis. Then, the relationships between their expression levels and GC patients' clinicopathological factors were further investigated. Receiver operating characteristic (ROC) curves were established for evaluating diagnostic values of hsa_circ_0067582 and hsa_circ_0005758. RESULTS: Compared with healthy control tissues, both hsa_circ_0067582 and hsa_circ_0005758 were significantly decreased in GC tissues. Besides, hsa_circ_0067582 expression was associated with GC patients' tissue CEA level (P <.001) and stages (P = .037); and hsa_circ_0005758 expression was relevant to tissue CEA level (P < .001) and perineural invasion (P = .048). The area under the ROC curve (AUC) of hsa_circ_0067582 was up to 0.671. The cutoff value was set at 10.61, with which the sensitivity and specificity were 55.2% and 75.0%, respectively. Similar to hsa_circ_0005758, the AUC of hsa_circ_0005758 was 0.721. The cutoff value was set at 10.20, with which the sensitivity and specificity were 75.0% and 67.7%, respectively. CONCLUSION: These results showed that both hsa_circ_0067582 and hsa_circ_0005758 may play an important role in gastric carcinogenesis; and they may be potential indicators for GC diagnosis.

Antibiotic resistance of Helicobacter pylori to 16 antibiotics in clinical patients.

BACKGROUND: Resistance of Helicobacter pylori (H. pylori) to antibiotics is increasing worldwide. To determine the status of H. pylori resistance and its patterns in clinical patients, an investigation utilizing susceptibility testing for commonly used antibiotics was needed. METHODS: Total of 2283 H. pylori strains were collected from 2013 to 2016. The resistance and its patterns of these strains were tested by agar dilution method. The resistance rate and minimal inhibition concentration (MIC) in different gender groups were also analyzed. RESULTS: The overall resistance rates were as following: amoxicillin (1.58%), clarithromycin (22.73%), levofloxacin (24.75%), furazolidone (1.49%), doxycycline (9.20%), cefetamet (97.20%), ceftriaxone (49.60%), cefuroxime (25.20%), gentamicin (3.73%), azithromycin (85.60%), rifampicin (2.80%), metronidazole (92.53%), ornidazole (94.27%), tinidazole (87.20%), ciprofloxacin (43.20%), and moxifloxacin (38.53%). There were only 64.08% strains pan-susceptible to amoxicillin, clarithromycin, levofloxacin, and furazolidone, followed by mono resistance (23.17%), double resistance (11.13%), triple resistance (1.36%), and quadruple resistance (0.26%). Significant differences in the resistance rate and MIC were also observed in different gender groups. CONCLUSION: Antibiotic resistance trends of H. pylori is increasing in clinical patients. With the increasing resistance, it is imperative to individualized therapy based on the results of drug susceptibility testing.

Low expression of hsa_circ_0006633 in human gastric cancer and its clinical significances.

Circular RNAs are new type of endogenous RNAs, which play an important role in the regulation of gene expression and indicate a great capacity in clinical diagnosis and treatments of diseases. However, the role of circular RNAs in gastric cancer remains unknown. In this study, we chose hsa_circ_0006633 as the target circular RNA and measured its levels in human gastric cancer tissues, plasma, and gastric cell lines by real-time quantitative reverse transcription polymerase chain reaction. Hsa_circ_0006633 levels at multiple stages of gastric tumorigenesis were then explored, and its relationships with clinicopathological features were analyzed as well. We found that the expression levels of hsa_circ_0006633 in four gastric cancer cell lines, HGC-27, SGC-7901, MGC-803, and AGS, were downregulated than those in normal gastric mucosal epithelial cell line GES-1. Then, we further detected that it was downregulated in 79.2% (76/96) gastric cancer tissues compared with the adjacent non-tumorous tissues. The lower expression of hsa_circ_0006633 was associated with cancer distal metastasis ( p = 0.037) and tissue carcinoembryonic antigen level ( p = 0.041). In addition, hsa_circ_0006633 expression was significantly decreased in gastritis and dysplasia tissues comparing with the healthy control. Moreover, plasma hsa_circ_0006633 levels were significantly increased in gastric cancer compared with healthy control. Our data imply that hsa_circ_0006633 may play an important role in gastric carcinogenesis and is also a potential biomarker for screening gastric cancer.

Decreased expression of hsa_circ_0001895 in human gastric cancer and its clinical significances.

Circular RNAs are a special class of endogenous RNAs characterized by jointing 3' and 5' ends together via exon or intron circularization. Recent studies found that circular RNAs are involved in the development of some human diseases. However, little is known about their roles in human gastric cancer. In this study, we chose hsa_circ_0001895 as a targeted circRNA to investigate its clinical significances in gastric cancer patients. Hsa_circ_0001895 expression levels in five gastric cancer cell lines and 257 specimens of tissues were measured by real-time quantitative reverse transcription polymerase chain reaction. Then, the potential relationship between hsa_circ_0001895 expression levels and patients' clinicopathological factors was investigated. A receiver operating characteristic curve was constructed for evaluating the diagnostic value of hsa_circ_0001895. Hsa_circ_0001895 expression levels in five detected gastric cancer cell lines (AGS, BGC-823, HGC-27, MGC-803, and SGC-7901) were all significantly downregulated than those in normal gastric epithelial GES-1 cells. Besides, compared with healthy control tissues, it was downregulated not only in 69.8% (67/96) gastric cancer tissues but also in gastric precancerous lesions. Moreover, hsa_circ_0001895 expression levels were significantly correlated with cell differentiation, Borrmann type, and tissue carcino-embryonic antigen expression. Our results suggested that hsa_circ_0001895 may play crucial roles during gastric cancerogenesis and is a potential biomarker for clinical prognosis prediction.

Using gastric juice lncRNA-ABHD11-AS1 as a novel type of biomarker in the screening of gastric cancer.

Long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis. However, the diagnostic values of most lncRNAs are largely unknown. To investigate whether gastric juice lncRNA-ABHD11-AS1 can be a potential biomarker in the screening of gastric cancer, 173 tissue samples and 130 gastric juice from benign lesion, gastric dysplasia, gastric premalignant lesions, and gastric cancer were collected. ABHD11-AS1 levels were detected by reverse transcription-polymerase chain reaction. Then, the relationships between ABHD11-AS1 levels and clinicopathological factors of patients with gastric cancer were investigated. The results showed that ABHD11-AS1 levels in gastric cancer tissues were significantly higher than those in other tissues. Its levels in gastric juice from gastric cancer patients were not only significantly higher than those from cases of normal mucosa or minimal gastritis, atrophic gastritis, and gastric ulcers but also associated with gender, tumor size, tumor stage, Lauren type, and blood carcinoembryonic antigen (CEA) levels. More importantly, when using gastric juice ABHD11-AS1 as a marker, the positive detection rate of early gastric cancer patients was reached to 71.4 %. Thanks to the special origin of gastric juice, these results indicate that gastric juice ABHD11-AS1 may be a potential biomarker in the screening of gastric cancer.

Reduced expression of the long non-coding RNA AI364715 in gastric cancer and its clinical significance.

Long non-coding RNA (lncRNA), which is greater than 200 nucleotides, is a class of RNA molecules without protein coding function. In recent years, studies have shown that lncRNAs are associated with cancers. They are affecting the occurrence and development of cancers. However, the diagnostic significances of lncRNAs in gastric cancer are largely unknown. In this study, we focused on AI364715, one typical lncRNA. A total of 186 samples were collected from two cancer centers. To find the potential association between its level and gastric cancer, we first collected 75 paired gastric cancer tissues and normal tissues, which are 5 cm away from the edge of carcinoma. Besides, 18 human healthy gastric mucosa and 18 gastric precancerous lesions (dysplasia) were also collected. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was first used to detect the expression level of AI364715 at multiple stages of gastric tumorigenesis. Then, the relationships between AI364715 level and the clinicopathological factors of patients with gastric cancer were analyzed. The results showed that the expression level of AI364715 in gastric cancer tissues was downregulated. Meanwhile, its expression level was closely associated with tumor size and differentiation. More importantly, AI364715 expression level was significantly changed in dysplasia, the typical precancerous lesions. Taken together, AI364715 may be a potential biomarker for the diagnosis of gastric cancer.

Plasma long noncoding RNA protected by exosomes as a potential stable biomarker for gastric cancer.

Long intergenic non-protein-coding RNA 152 (LINC00152) is one of the long noncoding RNAs (lncRNAs) abnormally expressed in gastric cancer tissues. However, its value in the diagnosis of gastric cancer is unclear. The aim of this study is to evaluate the clinical significance of plasma LINC00152 as a biomarker in the screening of gastric cancer and to explore the possible mechanism underling its stable existence in blood. We analyzed the levels of plasma LINC00152 in patients with gastric cancer and gastric epithelial dysplasia and healthy controls using quantitative reverse transcription polymerase chain reaction and then confirmed by sequencing. We also compared its levels in paired preoperative and postoperative plasma samples. In addition, we compared the levels of LINC00152 in plasma and in exosomes, which were extracted from the same plasma and confirmed by transmission electron microscopy. The levels of plasma LINC00152 were significantly elevated in gastric cancer patients compared with healthy controls. The sensitivity and specificity of plasma LINC00152 in the diagnosis of gastric cancer were 48.1 and 85.2%, respectively. There were no significant differences of LINC00152 levels between gastric epithelial dysplasia patients and healthy controls. LINC00152 levels in preoperative plasma samples were lower than those in postoperative ones. There were also no differences between LINC00152 levels in plasma and in exosomes. All these results suggested that LINC00152 can be detected in plasma, and one of the possible mechanisms of its stable existence in blood was protected by exosomes. It has the possibility to be applied in gastric cancer diagnosis as a novel blood-based biomarker.

[Surgical management of patients with pathologic complete response in the primary tumor after neoadjuvant chemotherapy for rectal cancer].

OBJECTIVE: To summarize and analyze the clinicopathological features and surgical management of patients with pathologic complete response (pCR) in the primary tumor after neoadjuvant chemotherapy for rectal cancer, and to explore the rational treatment of this entity. METHODS: Clinical data of fifty-two patients with locally advanced mid-low rectal cancer admitted to the Cancer Institute and Hospital, Chinese Academy of Medical Sciences from January 1994 to December 2013 were retrospectively analyzed. They were treated with neoadjuvant chemotherapy and achieved pathological complete response in the primary tumor. The preoperative clinical staging were stage II (cT3~4N0) in 10 cases and stage III (cT3~4N+) in 42 cases. After the neoadjuvant therapy, 10 cases achieved clinical complete response (cCR) (19.2%). RESULTS: Radical surgery was performed in 51 patients. Among them, five patients (9.8%) had pathological lymph node metastasis. One cCR patient underwent transanal local excision. The postoperative complication rate was 21.2%. During a median follow-up of 23.6 months, only one patient developed bone metastasis and another one had enlarged mesenteric and retroperitoneal lymph nodes detected by imaging. All the patients were alive by the last follow-up. The 2-year disease-free survival rate was 96.2% and overall survival rate was 100%. CONCLUSIONS: Radical surgery remains the standard therapy for cCR patients with rectal cancer after neoadjuvant chemotherapy. Local excision and "wait and see" should be recommended with great caution and limited to patients who cannot tolerate or refuse radical surgery with a strong demanding for sphincter saving, or applied in clinical trials.

Gastric juice long noncoding RNA used as a tumor marker for screening gastric cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) play a crucial role in tumorigenesis. However, the value of lncRNAs in the diagnosis of gastric cancer remains unknown. To identify whether lncRNA-AA174084 is a potential marker for the early diagnosis of gastric cancer (GC), the authors investigated its levels in tissues, blood, and gastric juices from patients with various stage of gastric tumorigenesis. METHODS: Total RNA in 860 specimens from patients and healthy controls was extracted. Levels of AA174084 in 134 paired GC tissues, 127 gastric mucosal tissues, 335 plasma samples, and 130 gastric juice samples at each stage of gastric tumorigenesis were measured using real-time reverse transcriptase-polymerase chain reaction analysis. The potential association between AA174084 levels and patients' clinicopathologic features were analyzed. A receiver operating characteristic (ROC) curve was constructed for differentiating GC patients from controls. RESULTS: Expression levels of AA174084 were down-regulated significantly in 95 of 134 GC tissues (71%) compared with the levels in paired, adjacent, normal tissues (P < .001). AA174084 levels had significant, negative correlations with age (P = .031), Borrmann type (P = .016), and perineural invasion (P = .032). Plasma AA174084 levels in patients with GC dropped markedly on day 15 after surgery compared with preoperative levels (P < .001) and were associated with invasion (P = .049) and lymphatic metastasis (P = .042). AA174084 levels in gastric juice from patients with GC were significantly higher than the levels in normal mucosa or in patients with minimal gastritis, gastric ulcers, and atrophic gastritis (P < .001). The area under ROC was up to 0.848 (P < .001). CONCLUSIONS: AA174084 may have potential as marker for the early diagnosis of GC.

Clinical significance of the low expression of FER1L4 in gastric cancer patients.

Long non-coding RNA (lncRNA) is a new class of regulative non-coding RNA, with a length larger than 200 nucleotides. Recent studies found that there are close relations between disregulative lncRNAs and human tumors. However, the clinical significances are largely unknown. In this study, we investigated the lncRNA-Fer-1-like protein 4 (FER1L4) level in gastric cancer tissues and plasma. The FER1L4 level in human tissues and plasma were measured by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Then, the correlations between the tissue or plasma FER1L4 levels and clinicopathological factors were assessed. A receiver operating characteristic (ROC) curve was constructed for differentiating GC patients from controls. Compared to matched adjacent non-tumorous tissues, FER1L4 expression levels in 91.80 % (56/61) of gastric cancer tissues are significantly decreased. The low FER1L4 level were associated with tumor size (p < 0.001), histologic grade (p = 0.001), general classification (p < 0.001), depth of invasion (p < 0.001), lymphatic metastasis (p < 0.001), distant metastasis (p = 0.003), TNM stage (p < 0.001), vessel or nerve invasion (p < 0.001 or p = 0.003), and serum CA72-4 (p < 0.001). The area under the ROC curve (AUC) was up to 0.778 (p < 0.001) and the sensitivity and specificity were 67.2 and 80.3 %, respectively. Also, plasma FER1L4 was detected by qRT-PCR. Our data show that there was no difference of plasma FER1L4 level between healthy person and preoperative gastric cancer patients, with a sharp decline in 63.9 % (53/83) of gastric cancer patients 2 weeks after surgery (p = 0.028). Taken together, FER1L4 might play a crucial role in human gastric cancer and may be a new potential biomarker for clinical prognosis evaluation.

Increased expression of long intergenic non-coding RNA LINC00152 in gastric cancer and its clinical significance.

It has been known that differential expression of long non-coding RNA (lncRNA) plays critical roles in carcinogenesis. However, the significance of lncRNA, especially long intergenic ncRNA (lincRNA, the main type of lncRNA family), in the diagnosis of gastric cancer is largely unknown. The aim of this study was to determine the expression level of LINC00152, a newfound lincRNA, in gastric carcinoma and its clinical association. The expression of LINC00152 in 71 pairs of tumorous and adjacent normal tissues from patients with gastric cancer was detected by quantitative real-time reverse transcription-polymerase chain reaction. And then, the potential associations between its level in gastric cancer tissue and the clinicopathological features were analyzed. Finally, a receiver operating characteristic (ROC) curve was constructed for differentiating patients with gastric cancer from patients with benign gastric diseases. The results showed that the expression level of LINC00152 in gastric carcinoma was significantly increased, compared with matched normal tissue (P=0.045) and normal mucosa from health control (P=0.004), respectively. Levels of LINC00152 in gastric cancer cell lines, BGC-823, MGC-803, and SGC-7901, were significantly higher than those in human normal gastric epithelial cell line GES-1. In addition, high expression of LINC00152 was correlated with invasion (P=0.042). LINC00152 levels in gastric juice from patients with gastric cancer were further found significantly higher than those from normal controls (P=0.002). Moreover, the area under the ROC curve (AUC) was up to 0.645 (95 % CI=0.559-0.740, P=0.003). This study highlights that lincRNA LINC00152 might be a novel biomarker for predicting gastric cancer.

lncRNA-AC130710 targeting by miR-129-5p is upregulated in gastric cancer and associates with poor prognosis.

Long noncoding RNAs (lncRNAs) play an important role in cancer occurrence and development. However, there is largely unknown about lncRNAs significance in the diagnosis and treatment of gastric cancer. In our study, we focused on AC130710, one of lncRNAs. Gastric cancer tissues and adjacent tissues were gathered from 78 patients with gastric cancer. The AC130710 levels were detected by reverse transcription polymerase chain reaction (RT-PCR). Then, we further analyzed the association between AC130710 level and the clinicopathological factors of patients with gastric cancer. Finally, the molecular mechanism underling AC130710 highly expressed in gastric cancer cells was explored. The results showed that AC130710 in cancer tissues from patients with gastric cancer was significantly higher than those in adjacent noncancerous tissues (P < 0.05). Its expression level was significantly associated with tumor size (P = 0.013), tumor-node-metastasis (TNM) stages (P = 0.030), and distal metastasis (P = 0.018). AC130710 expression in MGC-803 was significantly higher than that in normal gastric mucosa cell line GES-1 (P < 0.001). Moreover, miR-129-5p may play an important role in the downregulation of AC130710 in gastric cancer cells. These results indicated that lncRNA-AC130710 may be a potential tumor marker for gastric cancer prognosis.