Enhancing surgical outcomes in elderly gastric cancer patients: the role of comprehensive preoperative assessment and support.

BACKGROUND: As the prevalence of gastric cancer rises in aging populations, managing surgical risks and comorbidities in elderly patients presents a unique challenge. The Comprehensive Preoperative Assessment and Support (CPAS) program, through comprehensive preoperative assessments, aims to mitigate surgical stress and improve outcomes by enhancing patient awareness and preparation. This study investigates the efficacy of a CPAS program, incorporating frailty and sarcopenia evaluations, to improve short-term outcomes in elderly gastric cancer patients. METHODS: A retrospective analysis was conducted on 127 patients aged 75 or older who underwent surgery with CPAS between 2018 and August 2023, compared to 170 historical controls from 2012 to 2017. Propensity score matching balanced both groups based on age-adjusted Charlson Comorbidity Index and surgical details. The primary focus was on the impact of CPAS elements such as rehabilitation, nutrition, psychological support, oral frailty, and social support on short-term surgical outcomes. RESULTS: Among 83 matched pairs, the CPAS group, despite 40.4% of patients in the CPAS group and 21.2% in the control group had an ASA-PS score of 3 or higher (P < 0.001), demonstrated significantly reduced blood loss (100 ml vs. 190 ml, P = 0.026) and lower incidence of serious complications (19.3% vs. 33.7%, P = 0.034), especially in infections and respiratory issues. Sarcopenia was identified in 38.6% of CPAS patients who received tailored support. Additionally, the median postoperative hospital stay was notably shorter in the CPAS group (10 days vs. 15 days, P < 0.001), with no in-hospital deaths. These results suggest that personalized preoperative care effectively mitigates operative stress and postoperative complications. CONCLUSION: Implementing CPAS significantly enhances surgical safety and reduces complication rates in elderly gastric cancer patients, emphasizing the critical role of personalized preoperative care in surgical oncology for this demographic.

Early detection of occupational cholangiocarcinoma in a high-risk patient under intensive surveillance: a case study.

BACKGROUND: Occupational cholangiocarcinoma is associated with exposure to organic solvents, such as dichloromethane (DCM) and 1,2-dichloropropane (DCP). This report describes a case of occupational cholangiocarcinoma detected through regularly imaging following the discovery of elevated serum γ-glutamyl trans peptidase (γ-GTP) levels revealed during regular checkup. CASE PRESENTATION: A 43-year-old man who had been working in a printing company with 15 years of exposure to organic solvents presented to our hospital owing to abnormalities found during a routine checkup. Ultrasound (US) imaging revealed thickening of the gallbladder wall accompanied by gallstones, although in the blood tests, γ-GTP levels were within normal range. Given the high risk of cholangiocarcinoma development, the patient underwent regular monitoring with abdominal US and blood tests at a local doctor's office. At the age of 48, his serum γ-GTP level mildly elevated for the first time, prompting the initiation of semi-annual magnetic resonance cholangiopancreatography (MRCP). By the age of 50 years, dilation in B8 was detected, and one and a half years later, a tumor on the central side of the B8 dilation appeared. The patient was diagnosed with intrahepatic cholangiocarcinoma, which was treated with anterior sectionectomy. Pathological examination revealed an adenocarcinoma with a papillary glandular ductal structure at the root of the B8. In addition, biliary intraepithelial neoplasia (BilIN) and dysplasia have been identified around the tumor and periphery bile ducts and in noncancerous bile ducts. Postoperatively, the patient received 6 months of adjuvant chemotherapy with S-1monotherapy. Eight months after surgery, the patient remained under observation with no signs of recurrence. CONCLUSIONS: We report a case of occupational cholangiocarcinoma detected during a prolonged period of regular follow-up after exposure to DCM and DCP. Given the delayed carcinogenesis process, occupational cholangiocarcinomas manifest long after exposure to organic solvents, therefore, ongoing screening is extremely important. Vigilance is essential to avoid underdiagnosis, particularly for individuals who are at an increased risk of developing this form of cancer. Continuous monitoring is key to the early detection and effective management of occupational cholangiocarcinoma.

A comprehensive study on non-cancer-related mortality risk factors in elderly gastric cancer patients post-curative surgery.

BACKGROUND: The increasing incidence of gastric cancer in the elderly underscores the need for an in-depth understanding of the challenges and risks associated with surgical interventions in this demographic. This study aims to investigate the risk factors and prognostic indicators for non-cancer-related mortality following curative surgery in elderly gastric cancer patients. METHODS: This retrospective analysis examined 684 patients with pathological Stage I-III gastric cancer who underwent curative resection between January 2012 and December 2021. The study focused on patients aged 70 years and above, evaluating various clinical and pathological variables. Univariate analysis was utilized to identify potential risk factors with to non-cancer-related mortality and to access prognostic outcomes. RESULTS: Out of the initial 684 patients, 244 elderly patients were included in the analysis, with 33 succumbing to non-cancer-related causes. Univariate analysis identified advanced age (≥ 80 years), low body mass index (BMI) (< 18.5), high Charlson Comorbidity Index (CCI), and the presence of overall surgical complications as significant potential risk factors for non-cancer related mortality. These factors also correlated with poorer overall survival and prognosis. The most common cause of non-cancer-related deaths were respiratory issues and heart failure. CONCLUSION: In elderly gastric cancer patients, managing advanced age, low BMI, high CCI, and minimizing postoperative complications are essential for reducing non-cancer-related mortality following curative surgery.

A distal ileum malignant peripheral nerve sheath tumour after abdominal radiation therapy: case report of a rare tumour.

Malignant peripheral nerve sheath tumours (MPNSTs) are malignant tumours arising from a peripheral nerve or displaying nerve sheath differentiation. Most MPNSTs are found on the head, body trunk and extremities, whereas cases in the gastrointestinal are extremely rare. About half arise in neurofibromatosis type 1 patients and 10% arise post-irradiation. This is probably the first small bowel MPNST post-radiation therapy case reported. A 72-year-old female who received radiotherapy 30 years ago for cervical cancer was admitted with progressive abdominal pain and weight loss. Computed tomography revealed a mass with inhomogeneous enhancement in the lumen of the small intestine. Tumour excision was performed with ileocecal and sigmoid colon resection due to suspicion for peripheral tissue invasion. Histopathological examination revealed spindle-shaped cells with focal cartilage differentiation. Together with immunochemistry stain showing complete loss of H3K27me3, a final diagnosis of MPNST was made. The patient is presently under regular follow-ups, and has remained disease-free for 24 months.

A rare intrahepatic splenosis mimicking hepatocellular carcinoma: A case report.

Intrahepatic splenosis (IHS) is a rare disease that is considered to result from heterotopic autotransplantation or implantation of splenic tissue after splenic trauma or surgery. A 46-year-old man with a treatment history of a left lateral liver segmentectomy and splenectomy for a road traffic injury 30 years earlier presented to Sakai City Medical Center (Sakai, Japan) with acute abdominal pain in November 2019. Physical examination showed no significant signs, and serum data were normal. Computed tomography revealed a hypodense mass measuring 2.5x1.7 cm in segment 7 of the liver. Gadoxetic acid-enhanced magnetic resonance imaging showed early enhancement in the arterial phase and washout in the delayed phase. Therefore, laparoscopic surgery was performed with a preoperative diagnosis of hepatocellular carcinoma. Pathological examination of the tumor showed IHS. The postoperative course was uneventful, and the patient developed no new abnormal region in the liver during 2 years of follow-up. The present study presented a case of IHS assumed to be hepatocellular carcinoma. IHS should be considered as a differential diagnosis of a liver mass detected years after splenic trauma or surgery, even in cases with imaging patterns suggesting malignancy.

Subclonal accumulation of immune escape mechanisms in microsatellite instability-high colorectal cancers.

BACKGROUND: Intratumor heterogeneity (ITH) in microsatellite instability-high (MSI-H) colorectal cancer (CRC) has been poorly studied. We aimed to clarify how the ITH of MSI-H CRCs is generated in cancer evolution and how immune selective pressure affects ITH. METHODS: We reanalyzed public whole-exome sequencing data on 246 MSI-H CRCs. In addition, we performed a multi-region analysis from 6 MSI-H CRCs. To verify the process of subclonal immune escape accumulation, a novel computational model of cancer evolution under immune pressure was developed. RESULTS: Our analysis presented the enrichment of functional genomic alterations in antigen-presentation machinery (APM). Associative analysis of neoantigens indicated the generation of immune escape mechanisms via HLA alterations. Multiregion analysis revealed the clonal acquisition of driver mutations and subclonal accumulation of APM defects in MSI-H CRCs. Examination of variant allele frequencies demonstrated that subclonal mutations tend to be subjected to selective sweep. Computational simulations of tumour progression with the interaction of immune cells successfully verified the subclonal accumulation of immune escape mutations and suggested the efficacy of early initiation of an immune checkpoint inhibitor (ICI) -based treatment. CONCLUSIONS: Our results demonstrate the heterogeneous acquisition of immune escape mechanisms in MSI-H CRCs by Darwinian selection, providing novel insights into ICI-based treatment strategies.

Transducin Beta-Like 2 is a Potential Driver Gene that Adapts to Endoplasmic Reticulum Stress to Promote Tumor Growth of Lung Adenocarcinoma.

BACKGROUND: Endoplasmic reticulum (ER) stress has a close relation with cancer progression. Blocking the adaptive pathway of ER stress could be an anticancer strategy. Here, we identified an ER stress-related gene, Transducin beta-like 2 (TBL2), an ER-localized type I transmembrane protein, on increased chromosome 7q as a candidate driver gene of lung adenocarcinoma (LUAD). METHODS: The association between TBL2 mRNA expression and prognostic outcomes and clinicopathological factors was analyzed using The Cancer Genome Atlas (TCGA) datasets of LUAD and lung squamous cell carcinoma (LUSC). Localization of TBL2 in tumor tissues was observed by immunohistochemical staining. Gene set enrichment analysis (GSEA) was conducted using TCGA dataset. In vitro cell proliferation assays were performed using TBL2 knockdown LUAD cells, LUSC cells, and LUAD cells overexpressing TBL2. Apoptosis and ATF4 expression (ER stress marker) were evaluated by western blotting. RESULTS: TBL2 was overexpressed in LUAD and LUSC cells. Multivariate analysis indicated high TBL2 mRNA expression was an independent poor prognostic factor of LUAD. GSEA revealed high TBL2 expression was positively correlated to the ER stress response in LUAD. TBL2 knockdown attenuated LUAD cell proliferation under ER stress. TBL2 inhibited apoptosis in LUAD cells under ER stress. TBL2 knockdown reduced ATF4 expression under ER stress. CONCLUSIONS: TBL2 may be a novel driver gene that facilitates cell proliferation, possibly by upregulating ATF4 expression followed by adaptation to ER stress, and it is a poor prognostic biomarker of LUAD.

Convergent genomic diversity and novel BCAA metabolism in intrahepatic cholangiocarcinoma.

BACKGROUND: Driver alterations may represent novel candidates for driver gene-guided therapy; however, intrahepatic cholangiocarcinoma (ICC) with multiple genomic aberrations makes them intractable. Therefore, the pathogenesis and metabolic changes of ICC need to be understood to develop new treatment strategies. We aimed to unravel the evolution of ICC and identify ICC-specific metabolic characteristics to investigate the metabolic pathway associated with ICC development using multiregional sampling to encompass the intra- and inter-tumoral heterogeneity. METHODS: We performed the genomic, transcriptomic, proteomic and metabolomic analysis of 39-77 ICC tumour samples and eleven normal samples. Further, we analysed their cell proliferation and viability. RESULTS: We demonstrated that intra-tumoral heterogeneity of ICCs with distinct driver genes per case exhibited neutral evolution, regardless of their tumour stage. Upregulation of BCAT1 and BCAT2 indicated the involvement of 'Val Leu Ile degradation pathway'. ICCs exhibit the accumulation of ubiquitous metabolites, such as branched-chain amino acids including valine, leucine, and isoleucine, to negatively affect cancer prognosis. We revealed that this metabolic pathway was almost ubiquitously altered in all cases with genomic diversity and might play important roles in tumour progression and overall survival. CONCLUSIONS: We propose a novel ICC onco-metabolic pathway that could enable the development of new therapeutic interventions.

Minimizing invasiveness and simplifying the surgical procedure for upper and middle early gastric cancer with near-infrared light and organ traction.

BACKGROUND: Surgeons are often faced with optimal resection extent and reconstructive method problems in laparoscopic gastrectomy for gastric cancer in the upper and middle body of the stomach. Indocyanine green (ICG) marking and Billroth I (B-I) reconstruction were used to solve these problems with the organ retraction technique. CASE PRESENTATION: A 51-year-old man with upper gastrointestinal endoscopy revealed a 0-IIc lesion in the posterior wall of the upper and middle gastric body 4 cm from the esophagogastric junction. Clinical T1bN0M0 (clinical stage IA) was the preoperative diagnosis. Laparoscopic distal gastrectomy (LDG) and D1 + lymphadenectomy was decided to be performed considering postoperative gastric function preservation. The ICG fluorescence method was used to determine the accurate tumor location since the determination was expected to be difficult to the extent of optimal resection with intraoperative findings. By mobilizing and rotating the stomach, the tumor in the posterior wall was fixed in the lesser curvature, and as large a residual stomach as possible was secured in gastrectomy. Finally, delta anastomosis was performed after increasing gastric and duodenal mobility sufficiently. Operation time was 234 min and intraoperative blood loss was 5 ml. The patient was allowed to be discharged on postoperative day 6 without complications. CONCLUSION: The indication for LDG and B-I reconstruction can be expanded to cases where laparoscopic total gastrectomy or LDG and Roux-en-Y reconstruction has been selected for early-stage gastric cancer in the upper gastric body by combining preoperative ICG markings and gastric rotation method dissection.

Dynamic Changes in Peripheral Systemic Immunity Markers During Chemotherapy in HER2-negative Advanced Breast Cancer.

BACKGROUND/AIM: The immune system has a pivotal role in modulating the response to chemotherapy in breast cancer (BC). However, the immune status during chemotherapy remains unclear. We evaluated the sequential changes in peripheral systemic immunity markers in BC patients treated with various chemotherapeutic agents. MATERIALS AND METHODS: We examined the correlation between the peripheral systemic immunity markers, neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC) and the local cytolytic activity (CYT) score obtained by quantitative reverse-transcription polymerase chain reaction of 84 preoperative BC patients. Next, we observed the sequential changes in the peripheral systemic immunity markers during treatment with four anticancer drugs: oral 5-fluorouracil derivative; S-1, epirubicin plus cyclophosphamide; paclitaxel plus the anti-vascular endothelial growth factor antibody bevacizumab, and eribulin in 172 HER2-negative advanced BC patients. Finally, we examined the correlation between the changes in the peripheral systemic immunity markers, time to treatment failure (TTF) and progression-free survival (PFS). RESULTS: A negative correlation was found between ALC and NLR. ALC-low and NLR-high cases were positively associated with CYT score-low cases. The ratio of ALC-increase and NLR-decrease varies depending on the anticancer drugs used. The responder group (TTF ≥3 months) had a higher NLR-decrease ratio than the nonresponder group (TTF <3 months). Patients with a high NLR-decrease ratio showed higher PFS. CONCLUSION: The change in ALC or NLR varies according to the anticancer drugs, suggesting differential immunomodulatory effects of the drugs. Furthermore, the change in NLR reflects the therapeutic efficacy of chemotherapy in advanced BC.

[A Case of Locally Advanced Giant Sigmoid Colon Cancer Successfully Treated with Neoadjuvant Chemotherapy].

A 51-year-old woman presented to our hospital complaining of a lower abdominal mass and dysuria. She was diagnosed with advanced sigmoid colon cancer. The tumor was large, involving the bladder, and occupying the pelvic cavity. She received neoadjuvant chemotherapy with 4 courses of mFOLFOX6, in addition to panitumumab. The treatment resulted in a marked reduction of the tumor. A laparoscopic sigmoid colon resection, total cystectomy, neobladder reconstruction, complete uterine and bilateral adnexa resection and partial ileal resection were performed. The histopathological diagnosis was ypT4b(bladder), ypN0, ypStage Ⅱc, all with negative surgical margins. Adjuvant chemotherapy was not administered owing to the patient's refusal. She remained recurrence-free for 3 years of postoperative follow up.

Clinical Significance of Acylphosphatase 1 Expression in Combined HCC-iCCA, HCC, and iCCA.

BACKGROUND: Combined hepatocellular and cholangiocarcinoma is a rare primary liver cancer with histological features of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Little is known about the prognostic features and molecular mechanism of cHCC-iCCA. Acylphosphatase 1 is a cytosolic enzyme that produces acetic acid from acetyl phosphate and plays an important role in cancer progression. AIMS: We evaluated the clinical significance of ACYP1 expression in cHCC-iCCA, HCC, and iCCA. METHODS: ACYP1 immunohistochemistry was performed in 39 cases diagnosed with cHCC-iCCA. The prognosis was evaluated in three different cohorts (cHCC-iCCA, HCC, and iCCA). The relationships between ACYP1 expression and cell viability, migration, invasiveness, and apoptosis were examined using siRNA methods in vitro. In vivo subcutaneous tumor volumes and cell apoptosis were evaluated after downregulation of ACYP1 expression. RESULTS: Almost half of the patients with cHCC-iCCA were diagnosed with high ACYP1 expression. In all three cohorts, the cases with high ACYP1 expression had significantly lower overall survival, and high ACYP1 expression was identified as an independent prognostic factor. Downregulation of ACYP1 reduced the proliferative capacity, migration, and invasiveness of both HCC and iCCA cells. Moreover, knockdown of ACYP1 increased the ratio of apoptotic cells and decreased the expression of anti-apoptosis proteins. In vivo tumor growth was significantly inhibited by the transfection of ACYP1 siRNA, and the number of apoptotic cells increased. CONCLUSION: High ACYP1 expression could influence the prognosis of cHCC-iCCA, HCC, and iCCA patients. In vitro ACYP1 expression influences the tumor growth and cell viability in both HCC and iCCA by regulating anti-apoptosis proteins.

Successful laparoscopic conversion surgery for gastric cancer with para-aortic lymph node metastasis after third-line chemotherapy: a case report.

We herein reported a case of advanced gastric cancer (GC) with para-aortic lymph node (PALN) metastases who successful achieved downstaging following systemic chemotherapy and underwent curative laparoscopic conversion surgery. A 74-year-old male patient diagnosed with advanced GC and PALN metastases [cT4N3M1(LYM), stage IVA] was administered chemotherapy and immunotherapy for 28 months. After 27 courses of nivolumab as third-line chemotherapy, PALN enlargement was resolved, for which conversion surgery was planned. Subsequently, laparoscopic distal D2 gastrectomy with sampling para-aortic lymphadenectomy was performed, after which a pathological diagnosis of type V moderately differentiated tubular adenocarcinoma with mucinous adenocarcinoma, stage ypT3 (SS), ly1c, and v0, was established. The pathological proximal and distal tumor margins were negative. One lymph node metastasis was observed (No. 6; 1/25). The sampled lymph nodes were negative (No. 16a1: 0/2). The therapeutic effect was categorized as Grade 1a. The postoperative course was uneventful, with the patient receiving nivolumab to control for potential PALN metastases. Postoperatively, no recurrence was observed over 11 months. Laparoscopic conversion gastrectomy was successfully performed in a patient with advanced GC that was originally unresectable, suggesting that minimally invasive surgery may be a good option for originally unresectable advanced GC that becomes resectable.

Fanconi Anemia Complementation Group E, a DNA Repair-Related Gene, Is a Potential Marker of Poor Prognosis in Hepatocellular Carcinoma.

INTRODUCTION: Fanconi anemia complementation group E (FANCE) is a Fanconi anemia (FA) pathway gene that regulates DNA repair. We evaluated the clinical relevance of FANCE expression in hepatocellular carcinoma (HCC). METHODS: First, the associations between the expression of FA pathway genes including FANCE and clinical outcomes in HCC patients were analyzed in 2 independent cohorts: The Cancer Genome Atlas (TCGA, n = 373) and our patient cohort (n = 53). Localization of FANCE expression in HCC tissues was observed by immunohistochemical staining. Gene set enrichment analysis (GSEA) and gene network analysis (SiGN_BN) were conducted using the TCGA dataset. Next, an in vitro proliferation assay was performed using FANCE-knockdown HCC cell lines (HuH7 and HepG2). The association between mRNA expression of FANCE and that of DNA damage response genes in HCC was analyzed using TCGA and Cancer Cell Line Encyclopedia datasets. Finally, the association between FANCE mRNA expression and overall survival (OS) in various digestive carcinomas was analyzed using TCGA data. RESULTS: FANCE was highly expressed in HCC cells. Multivariate analysis indicated that high FANCE mRNA expression was an independent factor predicting poor OS. GSEA revealed a positive relationship between enhanced FANCE expression and E2F and MYC target gene expression in HCC tissues. FANCE knockdown attenuated the proliferation of HCC cells, as well as reduced cdc25A expression and elevated histone H3 pSer10 expression. SiGN_BN revealed that FANCE mRNA expression was positively correlated with DNA damage response genes (H2A histone family member X and checkpoint kinase 1) in HCC tissues. Significant effects of high FANCE expression on OS were observed in hepatobiliary pancreatic carcinomas, including HCC. CONCLUSIONS: FANCE may provide a potential therapeutic target and biomarker of poor prognosis in HCC, possibly by facilitating tumor proliferation, which is mediated partly by cell cycle signaling activation.

Pan-cancer methylome analysis for cancer diagnosis and classification of cancer cell of origin.

The accurate and early diagnosis and classification of cancer origin from either tissue or liquid biopsy is crucial for selecting the appropriate treatment and reducing cancer-related mortality. Here, we established the CAncer Cell-of-Origin (CACO) methylation panel using the methylation data of the 28 types of cancer in The Cancer Genome Atlas (7950 patients and 707 normal controls) as well as healthy whole blood samples (95 subjects). We showed that the CACO methylation panel had high diagnostic potential with high sensitivity and specificity in the discovery (maximum AUC = 0.998) and validation (maximum AUC = 1.000) cohorts. Moreover, we confirmed that the CACO methylation panel could identify the cancer cell type of origin using the methylation profile from liquid as well as tissue biopsy, including primary, metastatic, and multiregional cancer samples and cancer of unknown primary, independent of the methylation analysis platform and specimen preparation method. Together, the CACO methylation panel can be a powerful tool for the classification and diagnosis of cancer.

[Case of Robot-Assisted Low Anterior Resection with Total Cystectomy for Rectal Cancer Invading the Urinary Bladder/Prostate in Collaboration with Urologists].

We present a case of a 72-year-old man diagnosed with rectal cancer invading the urinary bladder/prostate. Preoperative chemoradiotherapy substantially reduced the tumor size. In collaboration with urologists, robot-assisted low anterior resection with total cystectomy was performed using the da Vinci Xi system. Depending on the surgical situation, the colorectal surgeon and urologist could smoothly and rapidly play the role of a console surgeon. Although the first robot-assisted multi-organ resection of our institution, the surgery was completed safely without any complications. Although the patient developed urinary tract infection postoperatively, he recovered and was discharged after postoperative 23 days. In conclusion, robot-assisted surgery would be useful in pelvic surgery involving multiple departments such as colorectal surgery, urology, and gynecology.

[Successful Treatment with TACE and RFA for a Hepatocellular Carcinoma Case with Lung Metastasis].

We report a hepatocellular carcinoma(HCC)case with lung metastasis that was successfully treated with transarterial chemoembolization(TACE)and percutaneous radiofrequency ablation(RFA). A man in his 60s took right robe liver resection for HCC after TACE for its rupture. Lung metastasis occurred at S1+2 and S6 in the left lung, and an adverse event interrupted standard molecular target therapies. Because extrahepatic metastasis had been seen only in these two locations for a long time, TACE was performed for both metastases. The feeders for both lesions were each intercostal artery, and controlling the drug inflow was necessary to avoid drug influx into the spinal cord branches when S6 metastasis was treated. The viable lesion remained in the S6 lesion, so RFA was added for both lung metastases. 100% tumor necrosis has been observed since the RFA.

[A Case Report of Stage â £b Thoracic Esophageal Cancer Responding to Multidisciplinary Treatment].

A 68-year-old man was referred to our hospital because of back pain during swallowing. Upper gastrointestinal endoscopy revealed a lower esophageal type 3 tumor. The patient was diagnosed with esophageal squamous cell carcinoma by the biopsy specimen. CT scan showed thoracic lower esophagus wall thickening, left paracardiac lymph node swelling, and a low-density area in the liver. Therefore, the patient was diagnosed with Stage Ⅳb esophageal cancer. After introducing cisplatin plus 5-FU combination therapy, the liver metastasis disappeared. After 9 chemotherapy courses, the patient received radical chemoradiotherapy. After completing chemoradiotherapy, the patient was followed up without any treatment. After 3 years since the treatment initiation, the patient is surviving without any relapse.

Oxysterol binding protein-like 3 (OSBPL3) is a novel driver gene that promotes tumor growth in part through R-Ras/Akt signaling in gastric cancer.

Gastric cancer (GC) is one of the most lethal malignant tumors. To improve the prognosis of GC, the identification of novel driver genes as therapeutic targets is in urgent need. Here, we aimed to identify novel driver genes and clarify their roles in gastric cancer. OSBPL3 was identified as a candidate driver gene by in silico analysis of public genomic datasets. OSBPL3 expression was analyzed by RT-qPCR and immunohistochemistry in GC cells and tissues. The biological functions and mechanisms of OSBPL3 in GC were examined in vitro and in vivo using GC cells. The association between OSBPL3 expression and clinical outcome in GC patients was also evaluated. Overexpression of OSBPL3 was detected in GC cells with OSBPL3 DNA copy number gains and promoter hypomethylation. OSBPL3-knockdown reduced GC cell growth in vitro and in vivo by inhibiting cell cycle progression. Moreover, an active Ras pull-down assay and western blotting demonstrated that OSBPL3 activates the R-Ras/Akt signaling pathway in GC cells. In a clinical analysis of two GC datasets, high OSBPL3 expression was predictive of a poor prognosis. Our findings suggest that OSBPL3 is a novel driver gene stimulating the R-Ras/Akt signaling pathway and a potential therapeutic target in GC patients.