Infiltrating characteristics and prognostic value of tertiary lymphoid structures in resected gastric neuroendocrine neoplasm patients.

Objectives: Tertiary lymphoid structures (TLSs) are lymphocyte aggregates that play an anti-tumor role in most solid tumors. However, the functions of TLS in gastric neuroendocrine neoplasms (GNENs) remain unknown. This study aimed to determine the characteristics and prognostic values of TLS in resected GNEN patients. Methods: Haematoxylin-eosin, immunohistochemistry (IHC) and multiple fluorescent IHC staining were used to assess TLS to investigate the correlation between TLSs and clinicopathological characteristics and its prognostic value. Results: Tertiary lymphoid structures were identified in 84.3% of patients with GNEN. They were located in the stromal area or outside the tumor tissue and mainly composed of B and T cells. A high density of TLSs promoted an anti-tumor immune response in GNEN. CD15+ TANs and FOXP3+ Tregs in TLSs inhibited the formation of TLSs. High TLS density was significantly associated with prolonged recurrence-free survival (RFS) and overall survival (OS) of GNENs. Univariate and multivariate Cox regression analyses revealed that TLS density, tumor size, tumor-node-metastasis (TNM) stage and World Health Organisation (WHO) classification were independent prognostic factors for OS, whereas TLS density, tumor size and TNM stage were independent prognostic factors for RFS. Finally, OS and RFS nomograms were developed and validated, which were superior to the WHO classification and the TNM stage. Conclusion: Tertiary lymphoid structures were mainly located in the stromal area or outside the tumor area, and high TLS density was significantly associated with the good prognosis of patients with GNEN. Incorporating TLS density into a nomogram may improve survival prediction in patients with resected GNEN.

Association between alcohol consumption and latent fasting blood glucose trajectories among midlife women.

Background: This investigation sought to elucidate the correlations between alcohol intake and trajectories of fasting blood glucose (FBG) among American women in midlife. Methods: Our analysis was rooted in the foundational data from the Study of Women's Health Across the Nation (SWAN), a comprehensive longitudinal study centered on US women during their midlife transition. We employed group-based trajectory modeling to chart the FBG trajectories spanning from 1996 to 2005. Employing logistic regression, we gauged the odds ratios (ORs) and 95% confidence intervals (CIs) to draw connections between initial alcohol consumption and FBG trajectory patterns, whilst controlling for predominant potential confounders. Results: Our cohort comprised 2,578 women in midlife, ranging in age from 42 to 52, each having a minimum of three subsequent FPG assessments. We discerned two distinct FBG trajectories: a low-stable pattern (n = 2,467) and a high-decreasing pattern (n = 111). Contrasted with the low-stable group, our data showcased an inverse relationship between alcohol intake and the high-decreasing FBG trajectory in the fully adjusted model 3. The most pronounced reduction was evident in the highest tertile of daily servings of alcoholic beverages (OR: 0.23, 95% CI: 0.10-0.52, p < 0.001), percentage of kilocalories sourced from alcoholic beverages (OR: 0.30, 95% CI: 0.16-0.58, p < 0.001), and daily caloric intake from alcoholic beverages (OR: 0.31, 95% CI: 0.16-0.62, p < 0.001). Conclusion: Moderate alcohol consumption may protect against high FPG trajectories in middle-aged women in a dose-response manner. Further researches are needed to investigate this causality in midlife women.

Enhanced Photodynamic Therapy Synergizing with Inhibition of Tumor Neutrophil Ferroptosis Boosts Anti-PD-1 Therapy of Gastric Cancer.

For tumor treatment, the ultimate goal in tumor therapy is to eliminate the primary tumor, manage potential metastases, and trigger an antitumor immune response, resulting in the complete clearance of all malignant cells. Tumor microenvironment (TME) refers to the local biological environment of solid tumors and has increasingly become an attractive target for cancer therapy. Neutrophils within TME of gastric cancer (GC) spontaneously undergo ferroptosis, and this process releases oxidized lipids that limit T cell activity. Enhanced photodynamic therapy (PDT) mediated by di-iodinated IR780 (Icy7) significantly increases the production of reactive oxygen species (ROS). Meanwhile, neutrophil ferroptosis can be triggered by increased ROS generation in the TME. In this study, a liposome encapsulating both ferroptosis inhibitor Liproxstatin-1 and modified photosensitizer Icy7, denoted LLI, significantly inhibits tumor growth of GC. LLI internalizes into MFC cells to generate ROS causing immunogenic cell death (ICD). Simultaneously, liposome-deliver Liproxstatin-1 effectively inhibits the ferroptosis of tumor neutrophils. LLI-based immunogenic PDT and neutrophil-targeting immunotherapy synergistically boost the anti-PD-1 treatment to elicit potent TME and systemic antitumor immune response with abscopal effects. In conclusion, LLI holds great potential for GC immunotherapy.

Cross-talk between gastric cancer and hepatic stellate cells promotes invadopodia formation during liver metastasis.

In gastric cancer (GC), the liver is a common organ for distant metastasis, and patients with gastric cancer with liver metastasis (GCLM) generally have poor prognosis. The mechanism of GCLM is unclear. Invadopodia are special membrane protrusions formed by tumor cells that can degrade the basement membrane and ECM. Herein, we investigated the role of invadopodia in GCLM. We found that the levels of invadopodia-associated proteins were significantly higher in liver metastasis than in the primary tumors of patients with GCLM. Furthermore, GC cells could activate hepatic stellate cells (HSCs) within the tumor microenvironment of liver metastases through the secretion of platelet-derived growth factor subunit B (PDGFB). Activated HSCs secreted hepatocyte growth factor (HGF), which activated the MET proto-oncogene, MET receptor of GC cells, thereby promoting invadopodia formation through the PI3K/AKT pathway and subsequently enhancing the invasion and metastasis of GC cells. Therefore, cross-talk between GC cells and HSCs by PDGFB/platelet derived growth factor receptor beta (PDGFRß) and the HGF/MET axis might represent potential therapeutic targets to treat GCLM.

Impact of environmental variables on the distribution of phytoplankton communities in the Southern Yellow Sea.

To gain a comprehensive understanding of the seasonal variation in the structure of phytoplankton communities in the Southern Yellow Sea (SYS), two research expeditions were conducted from 12 to 24 in April 2019, and from 12 to 22 in October of 2019. During the spring season, the phytoplankton community within the SYS was primarily comprised of diatoms and dinoflagellates, while in autumn, diatoms and cyanobacteria dominated. Thalassiosira rotula and Paralia sulcata were the dominant species in both seasons. In spring, P. sulcata displayed no obvious correlation with any environmental parameter, while in autumn, it exhibited negative correlations with environmental factors. According to the cluster and multidimensional scaling analyses, the phytoplankton community was stratified into three distinct ecological provinces in the SYS: the Western Yellow Sea, the Yellow Sea basin, and the southern coastal region. The phytoplankton community composition was predominantly affected by seasonal fluctuations in temperature and nutrient levels. Notably, the Yellow Sea basin exhibited the lowest phytoplankton abundance, largely because of the impact of the Yellow Sea Cold Water Mass. Furthermore, the presence of cyanobacteria, particularly prevalent in the Yellow Sea basin, may have been facilitated by transport mechanisms associated with the Kuroshio current. Aggregated boosted tree (ABT) and Generalized Additive models (GAM) suggested that temperature, DIN, salinity, and DIP were significant parameters of phytoplankton abundance in SYS. Additionally, the N:P nutrient ratio was a key parameter in governing the structure of phytoplankton communities during both seasons.

Lower Dietary Magnesium Is Associated with a Higher Hemoglobin Glycation Index in the National Health and Nutrition Examination Survey.

The data for the effect of dietary magnesium (Mg) on hemoglobin glycation index (HGI) is limited. Thus, this study aimed to examine the relationship between dietary Mg and HGI in the general population. Our research used data from the National Health and Nutrition Examination Survey from 2001 to 2002. The dietary intake of Mg was assessed by two 24-h dietary recalls. The predicted HbA1c was calculated based on fasting plasma glucose. Logistic regression and restricted cubic spline models were applied to assess the relationship between dietary Mg intake and HGI. We found a significant inverse association between dietary Mg intake and HGI (ß = - 0.00016, 95%CI: - 0.0003, - 0.00003, P = 0.019). Dose-response analyses revealed that HGI decreased with increasing intakes of Mg when reached the point above 412 mg/day. There was a linear dose-response relationship between dietary Mg intake and HGI in diabetic subjects, and there was an L-shape dose-response relationship in non-diabetic individuals. Increasing the intake of Mg might help lower the risk associated with high HGI. Further prospective studies are requested before dietary recommendations.

Risk factors of additional surgery after non-curative endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: The criteria for surgical intervention after non-curative endoscopic submucosal dissection (ESD) of early gastric cancer are unclear. We aimed to clarify the risk factors for residual cancer and lymph node metastasis after non-curative ESD and to identify recommendations for additional surgery. METHODS: We collected data on 133 consecutive patients who underwent additional surgery after non-curative ESD of early gastric cancer at Nanjing Drum Tower Hospital from January 2013 to July 2022. Univariate and multivariate analyses were performed to seek risk factors of residual cancer and lymph node metastasis. RESULTS: The incidence rates of residual cancer and lymph node metastasis were 13.5% (18/133) and 10.5% (14/133), respectively. There was neither residual tumor nor lymph node metastasis in 104 (78.2%) cases. Multivariate analyses elucidated that horizontal margin was an independent risk factor for local residual cancer, whereas lymphatic infiltration was an independent risk factor for lymph node metastasis. Patients with mixed histological types were more likely to suffer lymph node metastasis and further undergo additional surgery after non-curative ESD than pure histological type. CONCLUSIONS: Additional gastrectomy with lymph node dissection was strongly recommended in patients with lymphatic infiltration after non-curative ESD of early gastric cancer. Patients with mixed histological type have a high propensity for lymph node metastasis and should be treated as a separate subtype.

Prediction values of tertiary lymphoid structures in the prognosis of patients with left- and right-sided colon cancer: a multicenter propensity score-matched study.

BACKGROUND: Tertiary lymphoid structures (TLS) are the lymphocyte aggregates that play a key role in the vast majority of solid tumors including colon cancer, displaying an antitumor effect under most circumstances. The heterogeneity between left- and right-sided colon cancer (LCC and RCC) encompasses various aspects, such as clinical manifestations, pathological features, and immune responses. However, the function and prognostic significance of TLS within LCC and RCC have yet to be fully understood. METHODS: A retrospective analysis was performed on 2612 patients who underwent radical resection for LCC or RCC without distant metastasis in multiple medical centers. Utilizing propensity score matching, 121 patients with LCC and 121 patients with RCC were selected for the training set. An external validation set including 64 patients with LCC and 64 patients with RCC were also employed. Hematoxylin-eosin and immunohistochemical staining were used to assess TLS and the proportion of various immune cells. Clinical characteristics and prognostic values of TLS in patients with LCC and RCC were analyzed. Nomograms were constructed for LCC and RCC to predict 3-year and 5-year overall survival (OS), respectively. RESULTS: For LCC and RCC patients, TLS was located in the interstitial region or outside the tumor tissue and mainly consisted of B cells and T cells. The TLS quantity and density in RCC were higher than those of LCC. In multivariate Cox regression analysis, TLS density ( P =0.014), vascular invasion ( P =0.019), and AJCC stage ( P =0.026) were independent prognostic factors for 5-year OS of RCC. For LCC patients, AJCC stage ( P =0.024), tumor differentiation ( P =0.001), and tumor budding ( P =0.040) emerged as independent prognostic factors for 5-year OS. Similar results were obtained in the external verification set. Separate nomograms for RCC and LCC were developed, displaying improved prediction performance compared to the AJCC 8th edition TNM staging system. CONCLUSIONS: Differences in TLS quantity and density were observed between LCC and RCC, suggesting that a nomogram based on TLS density could more effectively predict survival for RCC patients. Furthermore, a nomogram based on tumor budding was recommended for better prediction of LCC patient survival. Taken together, these results suggested that the immune and clinical characteristics of colon cancer at left and right side were substantially different, which may lead to the use of different prediction model and the development of individual treatment strategy.

Mucosal-associated invariant T cells in digestive tract: Local guardians or destroyers?

Mucosa-associated invariant T cells (MAIT) are a class of innate-like T lymphocytes mainly presenting CD8+ phenotype with a semi-invariant αß T-cell receptor, which specifically recognises MR1-presented biosynthetic derivatives of riboflavin synthesis produced by various types of microbiomes. As innate-like T lymphocytes, MAIT can be activated by a variety of cytokines, leading to immediate immune responses to infection and tumour cues. As an organ that communicates with the external environment, the digestive tract, especially the gastrointestinal tract, contains abundant microbial populations. Communication between MAIT and local microbiomes is important for the homeostasis of mucosal immunity. In addition, accumulating evidence suggests changes in the abundance and structure of the microbial community during inflammation and tumorigenesis plays a critical role in disease progress partly through their impact on MAIT development and function. Therefore, it is essential for the understanding of MAIT response and their interaction with microbiomes in the digestive tract. Here, we summarised MAIT characteristics in the digestive tract and its alteration facing inflammation and tumour, raising that targeting MAIT can be a candidate for treatment of gastrointestinal diseases.

Tissue-resident memory T cells in gastrointestinal tumors: turning immune desert into immune oasis.

Tissue-resident memory T cells (Trm) are a particular type of T cell subgroup, which stably reside in tissues and have been revealed to be the most abundant memory T cell population in various tissues. They can be activated in the local microenvironment by infection or tumor cells and rapidly clean them up to restore homeostasis of local immunity in gastrointestinal tissues. Emerging evidence has shown that tissue-resident memory T cells have great potential to be mucosal guardians against gastrointestinal tumors. Therefore, they are considered potential immune markers for immunotherapy of gastrointestinal tumors and potential extraction objects for cell therapy with essential prospects in clinical translational therapy. This paper systematically reviews the role of tissue-resident memory T cells in gastrointestinal tumors and looks to the future of their prospect in immunotherapy to provide a reference for clinical application.

Turning Tertiary Lymphoid Structures (TLS) into Hot Spots: Values of TLS in Gastrointestinal Tumors.

Tertiary lymphoid structures (TLSs) are ectopic lymphocyte aggregation structures found in the tumor microenvironment (TME). Emerging evidence shows that TLSs are significantly correlated with the progression of gastrointestinal tumors, patients' prognosis, and the efficacy of adjuvant therapy. Besides, there are still some immunosuppressive factors in the TLSs that may affect the anti-tumor responses of TLSs, including negative regulators of anti-tumor immune responses, the immune checkpoint molecules, and inappropriate tumor metabolism. Therefore, a more comprehensive understanding of TLSs' responses in gastrointestinal tumors is essential to fully understand how TLSs can fully exert their anti-tumor responses. In addition, targeting TLSs with immune checkpoint inhibitors and vaccines to establish mature TLSs is currently being developed to reprogram the TME, further benefiting cancer immunotherapies. This review summarizes recent findings on the formation of TLSs, the mechanisms of their anti-tumor immune responses, and the association between therapeutic strategies and TLSs, providing a novel perspective on tumor-associated TLSs in gastrointestinal tumors.

Mixed Histologic Type is a Risk Factor for Lymph Node Metastasis in Submucosal Invasive Early Gastric Cancer.

INTRODUCTION: The treatment regimen for early gastric cancer (EGC) with mixed histologic type remains controversial. We aimed to clarify the relationship between mixed histologic type and lymph node metastasis (LNM) in EGC, with emphasis on submucosal invasive EGC. METHODS: We collected data on 730 consecutive EGC patients at Nanjing Drum Tower hospital between June 2010 and May 2019. Risk factors of LNM and overall survival were analyzed to compare the prognostic differences between different histologic types. RESULTS: Mixed-type EGC patients had higher LNM rates than differentiated-type patients (29.2 % versus 10.6 %, P < 0.001), while no significant difference was found between mixed-type and undifferentiated-type EGC patients (29.2% versus 24.0%, P = 0.225). Multivariate analyses identified tumor location (cardiac and bottom versus antrum), larger tumor size, submucosal invasion, histologic differentiation (undifferentiated-type, mixed-type versus differentiated-type), and lymphovascular invasion as independent risk factors for LNM in EGC patients. Subgroup analysis further elucidated that mixed histologic type was associated with LNM in submucosa invasive EGC, but not in mucosa-confined EGC. There was no statistical significance in overall survival and disease-specific survival of submucosal invasive EGC patients who underwent radical gastrectomy with lymphadenectomy between different histologic types (P = 0.151). CONCLUSIONS: Mixed histologic type may be an independent risk factor for LNM in submucosal invasive EGC. Curative resection with lymphadenectomy should be considered the appropriate treatment for submucosal invasive EGC with mixed histologic type.

Diversity, structure, and distribution of bacterioplankton and diazotroph communities in the Bay of Bengal during the winter monsoon.

The Bay of Bengal (BoB) is conventionally believed to be a low productive, oligotrophic marine ecosystem, where the diazotroph communities presumed to play a vital role in adding "new" nitrogen through the nitrogen fixation process. However, the diazotroph communities in the oceanic region of the BoB are still poorly understood though it represents most of the seawater volume. The present study investigated a detailed account of the bacterioplankton community structure and distribution in the oceanic BoB during the winter monsoon using high throughput sequencing targeting the 16S rRNA and nifH genes. Our study observed diverse groups of bacterioplankton communities in the BoB including both cyanobacterial and non-cyanobacterial phylotypes. Cyanobacteria (Prochlorococcus spp. and Synechococcus spp.) and Proteobacteria (mainly α-, γ-, and δ-Proteobacteria) were the most abundant groups within the bacterial communities, possessing differential vertical distribution patterns. Cyanobacteria were more abundant in the surface waters, whereas Proteobacteria dominated the deeper layers (75 m). However, within the diazotroph communities, Proteobacteria (mainly γ-Proteobacteria) were the most dominant groups than Cyanobacteria. Function prediction based on PICRUSt revealed that nitrogen fixation might more active to add fixed nitrogen in the surface waters, while nitrogen removal pathways (denitrification and anammox) might stronger in deeper layers. Canonical correspondence analysis (CCA) indicated that temperature, salinity, and silicate were major environmental factors driving the distribution of bacterial communities. Additionally, phosphate was also an important factor in regulating the diazotroph communities in the surface water. Overall, this study provided detailed information on bacterial communities and their vital role in the nitrogen cycles in oligotrophic ecosystems.

Molecular biology of pancreatic neuroendocrine tumors: From mechanism to translation.

Pancreatic neuroendocrine tumors (pNETs) are a group of heterogeneous tumors originated from progenitor cells. As these tumors are predominantly non-functional, most of them display asymptomatic characteristics, making it difficult to be realized from early onset. Therefore, patients with pNETs are usually diagnosed with metastatic disease or at a late disease stage. The relatively low incidence also limits our understanding of the biological background of pNETs, which largely impair the development of new effective drugs. The fact that up to 10% of pNETs develop in patients with genetic syndromes have promoted researchers to focus on the gene mutations and driver mutations in MEN1, DAXX/ATRX and mTOR signaling pathway genes have been implicated in disease development and progression. Recent advances in sequencing technologies have further enriched our knowledge of the complex molecular landscape of pNETs, pointing out crucial roles of genes in DNA damage pathways, chromosomal and telomere alterations and epigenetic dysregulation. These novel findings may not only benefit early diagnosis of pNETs, but also help to uncover tumor heterogeneity and shape the future of translational medical treatment. In this review, we focus on the current molecular biology of pNETs and decipher how these findings may translate into future development of targeted therapy.

A novel active mitochondrion-selective fluorescent probe for the NIR fluorescence imaging and targeted photodynamic therapy of gastric cancer.

The annual morbidity and mortality due to gastric cancer are still high across the world, posing a serious threat to public health. Improving the diagnosis rate of gastric cancer and exploring new treatments are urgent issues in the clinical field. In recent years, photosensitizer (PS)-based photodynamic therapy (PDT) has proven to be an effective cancer treatment strategy and can be used to treat a variety of cancers. Developing PSs with tumor-targeting ability and high singlet oxygen yield (Φ(1O2)) is the key to improving the PDT effect. Herein, we developed a novel diagnosis and treatment system (Cy1395-NPs). Our active thio-photosensitizer is based on the sulfur substitution strategy as it can reduce the S1-T1 energy gap, which can promote the process of intersystem crossing (ISC), thus resulting in high ROS generation efficiency. Cy1395-NPs exhibited stable spectral characteristics, satisfactory biocompatibility and high 1O2 yield under laser irradiation due to the introduction of the sulfur atom. In cellular studies, Cy1395-NPs could specifically target MKN45 cells via integrin αvß3-mediated cRGD endocytosis and selectively aggregate in the mitochondria. Cy1395-NPs had no obvious cytotoxicity for MKN45 cells and exerted obvious phototoxicity due to the production of 1O2 under laser irradiation. The in vivo results showed that the fluorescence signal from the tumor site was obviously enhanced in 16-48 h, and Cy1395-NPs could selectively target solid tumors with a retention time of about 32 h. Under laser irradiation, Cy1395-NPs significantly inhibited tumor growth and led to significant tumor suppression and apoptosis. In summary, the developed Cy1395-NPs could actively target tumors and exert mitochondrial selectivity, showing an excellent fluorescence imaging effect. Under the irradiation of an 808 nm laser, Cy1395-NPs achieved good inhibition of gastric cancer cells both in vitro and in vivo, thus displaying the functions of tumor targeting, mitochondrial selectivity, fluorescence imaging and tumor inhibition. Our strategy provides a new diagnostic and treatment method for gastric cancers in clinical settings.

Response of the Phytoplankton Sinking Rate to Community Structure and Environmental Factors in the Eastern Indian Ocean.

The phytoplankton sinking rate in the eastern Indian Ocean was measured during spring 2017 based on the SETCOL method. The range of phytoplankton sinking rates was -0.291 to 2.188 md-1, with an average of 0.420 ± 0.646 md-1. The phytoplankton sinking rate in the Equator (EQ) and the eastern boundary of the Indian Ocean near Sumatra (EB) was lower than that in the Bay of Bengal (BOB). The sinking rate above 100 m was low and increased rapidly below 100 m in all the three regions. The phytoplankton community composition had an important impact on the phytoplankton sinking rate in the east Indian Ocean. The strong stratification in BOB resulted in Trichodesmium spp. bloom and a lower phytoplankton diversity and evenness in BOB, while the phytoplankton in the deep layer are senescent cells that sink down from the upper layer and cannot actively regulate the state of the cells, resulting in a higher sinking rate. Depth and temperature have a great impact on the physiological state of phytoplankton. The sinking rate of phytoplankton depend on the dominant groups composing the phytoplankton community. For the eastern Indian Ocean, seawater stratification caused by temperature changes the distribution of nutrients in the upper layer, and phytoplankton are affected by temperature and nutrients, resulting in changes in community structure, and finally showing different subsidence characteristics.

Comparative Analysis of Total and Size-Fractionated Chlorophyll a in the Yellow Sea and Western Pacific.

Measurements of different size-fractionated chlorophyll a concentrations (Chl a) of phytoplankton assemblages in situ are vital for advancing our understanding of the phytoplankton size structure and thus the marine biogeochemical cycle. In the present study, we thus made a comparative analysis of total and size-fractionated Chl a in the Yellow Sea (YS) and Western Pacific (WP). Our results suggest that the total Chl a was highly variable in the YS (averaging ~1.02 µg L-1) and was generally 3-4-fold more than that in the WP (averaging ~0.30 µg L-1). The pico-sized Chl a had a significant contribution to total Chl a in the WP (range 75-88%), while the average contributions of the nano-sized and pico-sized Chl a to total Chl a in the YS were 47 and 38%, respectively, suggesting that a majority of the total Chl a in the YS was associated with nano- and picophytoplankton. Moreover, we applied the generalized additive models (GAMs) to explore the relationships between the total Chl a and that contained in each of the three size classes. These GAMs relationships suggested a continuum from picophytoplankton dominated waters to large phytoplankton (cells> 2 µm) domination with increasing Chl a. Finally, we made a comparison of the total Chl a obtained with GF/F filters and that measured from size-fractionated filtration and revealed that their corresponding concentrations are in good agreement, indicating the size-fractionated filtration had no effect on total Chl a determination.

Corrigendum: GPER1 Silencing Suppresses the Proliferation, Migration, and Invasion of Gastric Cancer Cells by Inhibiting PI3K/AKT-Mediated EMT.

[This corrects the article DOI: 10.3389/fcell.2020.591239.].

Histidine-rich calcium binding protein promotes gastric cancer cell proliferation, migration, invasion and epithelial-mesenchymal transition through Raf/MEK/ERK signaling.

Histidine-rich calcium binding protein (HRC) is a new type of Ca2+ homeostasis regulator, which acts as a nonnegligible role in regulating intracellular calcium homeostasis. Here, we demonstrated that HRC expression was upregulated in human gastric cancer (GC) samples, and its expression level was closely correlated with the overall survival (OS) rate of GC patients and the malignant potential of GC cell lines. Knockdown of HRC inhibited migration, invasion, and proliferation of GC cell lines in vitro, while HRC overexpression promoted GC cell migration, invasion, and proliferation in vitro, as well as the growth of subcutaneous tumors and peritoneal tumors in vivo. In terms of the mechanism, knockdown of HRC reduced the intracellular calcium ion level and the CaM protein level. Through cell function experiments, we found that HRC regulated the Raf/MEK/ERK pathway through Ca2+/CaM signaling and ultimately affected the epithelial­mesenchyme transition (EMT) of GC. In summary, we revealed that HRC represents a potential target for GC treatment.