BACKGROUND Gastric subepithelial tumors(SETs)may harbor potential malignancy.Although it is well recognized that large SETs should be resected,the precise treatment strategy remains controversial.Compared to surgical ...BACKGROUND Gastric subepithelial tumors(SETs)may harbor potential malignancy.Although it is well recognized that large SETs should be resected,the precise treatment strategy remains controversial.Compared to surgical resection,endoscopic resection(ER)has many advantages;however,ER of SETs in the cardia is challenging.AIM To evaluate the safety and efficacy of endoscopic full-thickness resection(EFTR)for the treatment of gastric cardia SETs.METHODS We retrospectively reviewed data from all patients with SETs originating from the muscularis propria layer in the gastric cardia that were treated by EFTR or submucosal tunneling ER(STER)at Zhongshan Hospital Fudan University between November 2014 and May 2022.Baseline characteristics and clinical outcomes,including procedure times and complications rates,were compared between groups of patients receiving EFTR and STER.RESULTS A total of 171 tumors were successfully removed[71(41.5%)tumors in the EFTR and 100(58.5%)tumors in the STER group].Gastrointestinal stromal tumors(GISTs)were the most common SET.The en bloc resection rate was 100%in the EFTR group vs 97.0%in STER group(P>0.05).Overall,the EFTR group had a higher complete resection rate than the STER group(98.6%vs 91.0%,P<0.05).The procedure time was also shorter in the EFTR group(44.63±28.66 min vs 53.36±27.34,P<0.05).The most common major complication in both groups was electrocoagulation syndrome.There was no significant difference in total complications between the two groups(21.1%vs 22.0%,P=0.89).CONCLUSION EFTR of gastric cardia SETs is a very promising method to facilitate complete resection with similar complications and reduced operative times compared to STER.In cases of suspected GISTs or an unclear diagnosis,EFTR should be recommended to ensure complete resection.展开更多
The heterotopic pancreas, which is usually described as an untypical presence of pancreatic tissue without any anatomic or vascular continuity with the pancreas, is relatively rare. Clinical manifestations may include...The heterotopic pancreas, which is usually described as an untypical presence of pancreatic tissue without any anatomic or vascular continuity with the pancreas, is relatively rare. Clinical manifestations may include bleeding, inflammation, pain and obstruction; however, in most cases it remains silent and is diagnosed during autopsy. Here, we report a case of ectopic pancreatic lesion located in the gastric cardia. The patient was a 73-year-old woman who had a history (over four months) of chronic epigastric pain accompanied by heartburn. Esophagogastroduodenoscopy revealed inflammatory changes throughout the stomach and lower esophagus, as well as a flat polypoid mass with benign features located in the gastric cardia, approx. 10 mm below the “Z” line, measuring approx. 7 mm in diameter. Endoscopic biopsy forceps were used to remove the lesion. Histological examination of the lesion revealed the presence of heterotopic pancreatic tissue in the gastric mucosa. On the basis of the presented case, we suggest that pancreatic ectopia should be a part of differential diagnosis, not only when dealing with submucosal gastric lesions, but also with those that are small, flat and/or untypically located.展开更多
AIM To evaluate the clinical and prognostic significance of preoperative and postoperative cytokeratin 19(CK19) and carcinoembryonic antigen(CEA) m RNA levels in peripheral blood of patients with gastric cardia cancer...AIM To evaluate the clinical and prognostic significance of preoperative and postoperative cytokeratin 19(CK19) and carcinoembryonic antigen(CEA) m RNA levels in peripheral blood of patients with gastric cardia cancer(GCC).METHODS We detected the preoperative and postoperative mR NA levels of CK19 and CEA in peripheral blood of 129 GCC patients by using reverse transcription-polymerase chain reaction and evaluated their clinical and prognostic significance by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard analysis. A new prognostic model which stratified patients into three different risk groups was established based on the independent prognostic factors.RESULTS Elevated preoperative and postoperative CK19 and CEA mR NA levels in peripheral blood of GCC patients were associated with lymph node metastasis. Univariate analysis showed that tumor size, histological grade, depth of tumor invasion, lymph node metastasis, preoperative CK19 m RNA, and preoperative and postoperative CEA m RNA levels were correlated with the prognosis of GCC patients. The multivariate analysis showed that lymph node status(P = 0.018), preoperative CK19(P = 0.035) and CEA(P = 0.011) m RNA levels were independent prognostic factors for overall survival(OS). The 5-year OS rates for the low-, intermediate-, and high-risk groups were 48.3%, 22.6%, and 4.6%, respectively(P < 0.001).CONCLUSION Elevated preoperative CK19 and CEA mR NA levels may be regarded as promising biomarkers for predicting lymph node metastasis and poor prognosis in patients with GCC. This new prognostic model may help us identify the subpopulations of GCC patients with the highest risk.展开更多
Objective: This study aimed to determine if gastric cardia adenocarcinoma(GCA) risk was associated with the lys(A or *2) allele at the rs671(glu504lys) polymorphism within the aldehyde dehydrogenase 2(ALDH2) gene in a...Objective: This study aimed to determine if gastric cardia adenocarcinoma(GCA) risk was associated with the lys(A or *2) allele at the rs671(glu504lys) polymorphism within the aldehyde dehydrogenase 2(ALDH2) gene in a Chinese Han population. We also aimed to investigate ALDH2 genotypic distributions between subjects from high- and low-incidence areas for both GCA and esophageal squamous cell carcinoma(ESCC).Methods: We designed a case-control study including 2,686 patients with GCA and 3,675 control subjects from high- and lowincidence areas for both GCA and ESCC in China. Taq Man allele discrimination assay was used to genotype the rs671 polymorphism. χ~2 test and binary logistic regression analysis were used to estimate the odds ratios for the development of GCA,and multivariate ordinal logistic regression was used to analyze ALDH2 genotypic distributions among different groups.Results: Compared with ALDH2*1/*1 homozygotes, ALDH2*1/*2 and ALDH2*2/*2 carriers did not increase the risk for GCA in the Chinese Han population(P>0.05). Interestingly, the ratio of homozygous or heterozygous ALDH2 *2 carriers in highincidence areas for both GCA and ESCC was lower than that in low-incidence areas(P<0.001).Conclusions: Genotypes of rs671 at ALDH2 may not increase GCA susceptibility in Chinese Han populations. In addition, the ALDH2 genotypic distribution differs between Chinese Han populations from high- and low-incidence areas for both GCA and ESCC. Our findings may shed light on the possible genetic mechanism for the dramatic geographic differences of GCA occurrence in China.展开更多
AIM: To characterize the histochemical type and pattern of intestinal metaplasia (IM) adjacent to gastric cardia adenocarcinoma (GCA) and distal gastric cancer (GC) in Unzhou, Henan Province, China. METHODS: A...AIM: To characterize the histochemical type and pattern of intestinal metaplasia (IM) adjacent to gastric cardia adenocarcinoma (GCA) and distal gastric cancer (GC) in Unzhou, Henan Province, China. METHODS: Alcian-blue-periodic acid Schiff and high iron diamine-Alcian blue histochemical methods were performed on 142 cases of IM, including 49 cases of GCA and 93 cases of GC. All the patients were from Linzhou, Henan Province, China, the highest incidence area for both GCA and squamous cell carcinoma. Radio- or chemotherapy was not applied to these patients before surgery. RESULTS: The detection rate of IM in tissues adjacent to GCA tissues was 44.9%, which was significantly lower than that in GC tissues (80.64%, P〈0.01). The rates of both incomplete small intestinal and colonic IM types identified by histochemistry in GCA tissues (31.82% and 63.64%, respectively) were significantly higher than those in GC (5.33% and 21.33%, respectively, P〈0.01). CONCLUSION: IM in GCA and GC should be considered as a separate entity. Further research is needed to evaluate whether neoplastic progression of IM is related to its mucin profile in GCA.展开更多
AIM: To analyze retrospectively, our results about patients who underwent surgical treatment for adenocarcinoma of the cardia in relation to age, in order to evaluate surgical problems and prognostic factors. METHODS...AIM: To analyze retrospectively, our results about patients who underwent surgical treatment for adenocarcinoma of the cardia in relation to age, in order to evaluate surgical problems and prognostic factors. METHODS: From January 1987 to March 2003, 140 patients with adenocarcinoma of the cardia underwent resection in the authors' institution. They were divided into three groups with regard to age. Patients 〈70 and 〉 60 year old (31) were excluded; we also excluded 18 out of 109 patients with poor general status or systemic metastases. So, we compared 51 elderly (≥ 70 year old) and 58 younger patients (≤ 60 year old). The treatment was esophagectomy for type I tumors, and extended gastrectomy and distal esophagectomy for type Ⅱ and Ⅲ lesions. RESULTS: Laparotomy was carried out in 91 patients (83.4%), 38 in the elderly (74.5%) and 53 in younger patients (91.3%, P〈0.05). Primary resection was performed in 81 cases (89%) without significant differences between the two groups. Postoperative death was higher in the elderly (12.1%) than the other group (4.1%, P〈0.05), while morbidity was similar in both groups. A curative resection (R0) was performed in 59 patients (72.8%), 69.6% in the elderly and 75% in the younger group (P〉0.05). The overall 3- and 5-year survival rates were 26.7% and 17.8% respectively for the elderly and 40.7% and 35.1% respectively for younger patients (P = 0.1544). Survival rates were significantly associated with R0 resection, pathological node-poskive category and tumor differentiation in both groups.CONCLUSION: As the age of the general population increases, more elderly patients with gastric cardia cancer will be candidates for surgical resection. Age alone should not preclude surgical treatment in elderly patients with gastric cardia cancer and a tumor resection can be carried out safely. Certainly, we should take care in defining the surgical treatment in elderly patients, particularly as regarding the surgical approach; although the surgical approach does not influence the survival rate, the transhiatal way still remains the best one due, to the lower incidence of respiratory morbidity and thoracic pain.展开更多
BACKGROUND Gastric cardia adenocarcinoma(GCA),which has been classified as type II adenocarcinoma of the esophagogastric junction in western countries,is of similar geographic distribution with esophageal squamous cel...BACKGROUND Gastric cardia adenocarcinoma(GCA),which has been classified as type II adenocarcinoma of the esophagogastric junction in western countries,is of similar geographic distribution with esophageal squamous cell carcinoma in China,and even referred as"sister cancer"by Chinese oncologists.The molecular mechanism for GCA is largely unknown.Recent studies have shown that decreased expression of E-cadherin is associated with the invasion and metastasis of multiple cancers.However,the E-cadherin expression has not been well characterized in gastric cardia carcinogenesis and its effect on GCA prognosis.AIM To characterize E-cadherin expression in normal gastric cardia mucosa,dysplasia and GCA tissues,and its influence on prognosis for GCA.METHODS A total of 4561 patients with GCA were enrolled from our previously established GCA and esophageal cancer databases.The enrollment criteria included radical surgery for GCA,but without any radio-or chemo-therapy before operation.The GCA tissue from 4561 patients and matched adjacent normal epithelial tissue(n=208)and dysplasia lesions(n=156)were collected,and processed as tissue microarray for immunohistochemistry.The clinicopathological characteristics were retrieved from the medical records in hospital and follow-up was carried out through letter,telephone or home interview.E-cadherin protein expression was determined by two step immunohistochemistry.Kaplan–Meier and Cox regression analyses were used to correlate E-cadherin protein expression with survival of GCA patients.RESULTS Of the 4561 GCA patients,there were 3607 males with a mean age of 61.6±8.8 and 954 females with a mean age of 61.9±8.6 years,respectively.With the lesions progressed from normal gastric cardia mucosa to dysplasia and GCA,the positive immunostaining rates for E-cadherin decreased significantly from 100%to 93.0%and 84.1%,respectively(R2=0.9948).Furthermore,E-cadherin positive immunostaining rate was significantly higher in patients at early stage(0 and I)than in those at late stage(II and III)(92.7%vs 83.7%,P=0.001).E-cadherin positive expression rate was significantly associated with degree of differentiation(P=0.001)and invasion depth(P<0.001).Multivariate analysis showed that the GCA patients with positive E-cadherin immunostaining had better survival than those with negative(P=0.026).It was noteworthy that E-cadherin positive expression rate was similar in patients with positive and negative lymph node metastasis.However,in patients with negative lymph node metastasis,those with positive expression of E-cadherin had better survival than those with negative expression(P=0.036).Similarly,in patients with late stage GCA,those with positive expression of E-cadherin had better survival than those with negative expression(P=0.011).CONCLUSION E-cadherin expression may be involved in gastric cardia carcinogenesis and low expression of E-cadherin may be a promising early biomarker and overall survival predictor for GCA.展开更多
The factors associated with an increase in gastric cardia adenocarcinoma are poorly understood.Environmental factors such as Helicobacter pylori(H.pylori) infection and diet have been hypothesized to play a role in th...The factors associated with an increase in gastric cardia adenocarcinoma are poorly understood.Environmental factors such as Helicobacter pylori(H.pylori) infection and diet have been hypothesized to play a role in the recently increased risk of this disease,but additional studies are needed.In conducting studies to establish the relationship between potential risk factors and gastric cardia adenocarcinoma,it is necessary to carefully consider the role of bias.In a recently published study,the reported associations between H.pylori as well as post-meal physical exertion and gastric cardia adenocarcinoma may have been greatly influenced by selection bias.展开更多
Objective: To investigate the association between gastric cardia adenocarcinoma (GCA) and ten functional single nueleotide polymorphisms (SNPs), including TPY3BPI rs560191 G〉C, CASP8 rs1035142 G〉T, CASP7 rs3127...Objective: To investigate the association between gastric cardia adenocarcinoma (GCA) and ten functional single nueleotide polymorphisms (SNPs), including TPY3BPI rs560191 G〉C, CASP8 rs1035142 G〉T, CASP7 rs3127075 G〉C, CASP7 rs7907519 C〉A, and six C1 orf 10/CRNN variants. We performed a hospital- based case-control study to evaluate the genetic effects of these SNPs. Methods: Two hundred and forty-three GCA cases and 476 controls were enrolled in this study. A custom- by-design 48-Plex SNPscanTM Kit was used to determine their genotypes. Results: When the TP^3BP1 rs560191 GG homozygote genotype was used as the reference group, the GC genotype was associated with a significantly increased risk of GCA. The CC genotype was not associated with the risk of GCA compared with the GG genotype. None of the CASP8 rs1035142 G〉T, CASP7 rs3127075 G〉C, CASP7 rs7907519 C〉A or the six ClorflO/CRNN polymorphisms showed a significant difference in genotype distributions between the cases and the controls. Conciusions: The results demonstrated that the functional polymorphism TP53BPI rs560191 G〉C might contribute to GCA susceptibility. However, the statistical power of our study was limited. Large, well- designed studies and further functional investigations are needed to confirm our findings.展开更多
OBJECTIVE: To determine the value of resection of combined visceral organs in surgical treatment of gastric cardiac carcinoma. METHODS: We retrospectively analyzed 217 random patients with carcinoma of the gastric c...OBJECTIVE: To determine the value of resection of combined visceral organs in surgical treatment of gastric cardiac carcinoma. METHODS: We retrospectively analyzed 217 random patients with carcinoma of the gastric cardia who underwent a gastric cardiac resection. The patients had been treated as follows: 186 with partial gastrectomy, 31 with total gastrectomy, 97 with a combined-visceral resection, of which 82 underwent a splenectomy plus partial pancreatectomy, 10 with splenectomy alone and 5 with partial hepatectomy and diaphragmatectomy. RESULTS: The total patients were divided into 3 groups: 128 with a gastrectomy alone, 10 with gastrectomy and splenectomy, and 82 with gastrectomy and splenectomy plus pancreatectomy. The operating times for these 3 groups were respectively 3.0 h, 3.1 h and 3.8 h. The hospitalization times were respectively 23.8 d, 31.2 d and 25.9 d. No differences in post-operative complications were found between these 3 groups. There were 92 patients who underwent a gastrectomy combined with a splenectomy and (or) the pancreatectomy, in which 92 No.10 lymph nodes were eliminated, with an average of one in each patient. Among the 125 patients not receiving a splenectomy but with elimination of lymph nodes, 82 underwent a gastrectomy combined with partial pancreatectomy, of which 107 lymph nodes were eliminated for the No. 11 group, with an average of 1.3 in each patient. There was a statistically significant difference between the 2 groups. The overall survival rates were similar in the 3 groups showing no statistical differences, but was higher in the Stage Ⅲ patients with a combined resection of multi-organs. For patients in the Stage Ⅳ without resection of multi-organs, the survival rate was higher, but there was no significant difference between the 2 groups. CONCLUSION: It is difficult to determine precisely the involvement of para-tumorous organs with the eye during an operation. Combining a splenectomy with a pancreatectomy does not increase the post-operative complications following surgical treatment for carcinoma of the gastric cardia. The combination of a splenectomy and partial pancreatectomy results in a higher survival rate and has an important significance for eliminating the lymph nodes of group 10 and 11, especially for patients in Stage Ⅲ. In the application of a resection combining multi-organs, the doctor should make every effort to decrease the trauma and the complications based on the condition that the cancerous tissue is totally resected.展开更多
AIM:To investigate the relationship between human papillomavirus (HPV) infection and concurrent esophagus and gastric cardia cancer from the same patient (CC) and examine the significance of P16 INK4A protein expressi...AIM:To investigate the relationship between human papillomavirus (HPV) infection and concurrent esophagus and gastric cardia cancer from the same patient (CC) and examine the significance of P16 INK4A protein expression.METHODS:Polymerase chain reaction was used to detect the presence of HPV type16 (HPV16).The expression of P16 INK4A protein was detected using immunohistochemistry.RESULTS:Among the CC specimens,HPV16-DNA was found in eight cases of esophageal squamous cell carcinoma (ESCC) and five cases of gastric cardia adenocarcinoma (GCA),respectively (47% vs 29%),and two of both ESCC and GCA.P16 INK4A was highly expressed in both ESCC and GCA.In the HPV-associated positive CC,higher P16 INK4A expression was observed in the GCA than in the ESCC (75% vs 25%,P < 0.05).CONCLUSION:HPV16 as a correlated risk factor may play an important role in the development of ESCC and GCA.P16 INK4A may be a screening index in the HPVassociated carcinoma of gastric cardia.展开更多
Gastric gastrointestinal stromal tumor (GIST), esophageal squamous cell carcinoma and gastric cardia adenocarcinoma are distinct neoplasms originating from different cell layers; therefore, simultaneous development of...Gastric gastrointestinal stromal tumor (GIST), esophageal squamous cell carcinoma and gastric cardia adenocarcinoma are distinct neoplasms originating from different cell layers; therefore, simultaneous development of such carcinomas is relatively rare. Auxiliary examinations revealed coexistence of esophageal and gastric cardia carcinoma with lymph node metastasis in a 77-year-old man. Intraoperatively, an extraluminal tumor (about 6.0 cm × 5.0 cm × 6.0 cm) at the posterior wall of the gastric body, a tumor (about 2.5 cm × 2.0 cm) in the lower esophagus, and an infiltrative and stenosing tumor (about 1.0 cm × 2.0 cm) in the gastric cardia were detected. Wedge resection for extraluminal gastric tumor, radical esophagectomy for lower esophageal tumor, and cardiac resection with gastroesophageal (supra-aortic arch anastomoses) were performed. Postoperative histological examination showed synchronous occurrence of gastric GIST, esophageal squamous cell carcinoma, and gastric cardia adenocarcinoma. Furthermore, immunohistochemistry indicated strong staining for c-Kit/CD117, Dog-1, Ki-67 and smooth muscle, while expression of S-100 and CD34 was negative.展开更多
Background In China, esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) share susceptibility loci, but different rates of multiple primary cancer and male/female ratio suggest the pr...Background In China, esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) share susceptibility loci, but different rates of multiple primary cancer and male/female ratio suggest the proportion of familial cancer is not equal. Methods The percent of cases with a positive family history, median onset age, rate of multiple primary cancer, and male/female ratio associated with upper, middle, lower third ESCC and GCA were compared to reveal the proportion of familial cancer. The 7267 subjects analyzed constituted all ESCC and GCA cases in whom the cancer was resected with cure intention between 1970 and 1994 at the 4th Hospital of Hebei Medical University. Results A positive family history for cancer was most often associated with the multiple primary ESCC and/or GCA cases, e.g. with 42% of the males and 59% of the females. For upper, middle, lower third ESCC and GCA, the percent of cases with a positive family history decreased by 38.5%, 26.3%, 26.5%, and 11.2% in males (P 〈0.000) and 25.0%, 22.3%, 23.9%, and 9.8% in females (P 〈0.0001). Median onset age increased from 49, 52, 55, to 56 years old in males and from 50, 53, 55, to 56 years old in females ( both P 〈0.0001) for upper, middle, lower third ESCC and GCA. Male/female ratio increased from 2.2, 2.1, 2.2, to 6.2:1 for upper, middle, lower third ESCC and GCA (P〈0.0001). For upper, middle, lower third ESCC and GCA, the percent of multiple primary cancers decreased from 21.2%, 2.3%, 2.2%, to 1.5% in males and from 14.3%, 2.4%, 3.4%, to 3.1% in females. The preponderance of males, smoking, drinking, or onset-age 〉50 years was significantly higher in GCA than in ESCC, and the difference in the rates of multiple primary cancers between the preponderant and the non-preponderant cases was significant in GCA, but not in ESCC, suggesting non-equal requirement for genetic susceptibility when environmental hazards did not exist. Conclusions The proportion of familial cancer in upper gastrointestinal carcinomas decreases by the priamry site of upper, middle, lower third esophagus and gastric cardia. Considering familial and sporadic cancers differ in preventability, screening strategy and recurrence, our findings have basic and clinical implications.展开更多
Background Gastroesophageal junction adenocarcinomas include adenocarcinomas of the distal esophagus (DE) and gastric cardia (GC). It is controversial whether these tumors are the same entity and whether they have...Background Gastroesophageal junction adenocarcinomas include adenocarcinomas of the distal esophagus (DE) and gastric cardia (GC). It is controversial whether these tumors are the same entity and whether they have the same survival rates. Patients with DE and GC adenocarcinomas have a similar survival rate in the US; however, data are lacking in Asian countries. Therefore, we conducted a retrospective study to understand the implications of the tumor location in the survival of Asian patients. Methods A total of 209 patients with pathologically confirmed DE and GC adenocarcinomas, from 2005 to 2007, were included in the study. We identified patients with adenocarcinomas of the DE (DE group, n=91) and GC (GC group) (n=118), We performed an unadjusted survival analysis using the Kaplan-Meier method, and used a Cox proportional hazards regression model to adjust for potential confounding covariates. Results We found no significant difference between the overall survival of the DE and GC groups. The 3-year survival rates were 44.8% and 53.0%, respectively, and the 5-year survival rates were 27.9% and 30.2%, respectively (P=0.162). We found no significant difference in early staging, advanced staging, different T staging, and different N staging, between the groups. Both advanced post-operative N staging and advanced AJCC staging had a significant adverse effect on survival. Conclusions Patients with DE and GC adenocarcinomas have similar survival rates in the Asian population. Both post-operative N staging and AJCC staging are prognostic factors.展开更多
From January 1970 to June 1999, 141 patients with superficial esophageal and cardiac carcinomas (SEC and SCC) underwent surgical treatment, Of the 141 patients 128 (90.8%) had slight symptoms related to swallowing, an...From January 1970 to June 1999, 141 patients with superficial esophageal and cardiac carcinomas (SEC and SCC) underwent surgical treatment, Of the 141 patients 128 (90.8%) had slight symptoms related to swallowing, and the remaining 13 (9.2%) were asymptomatic, Balloon cytology and esophagoscopy proved very useful for the diagnosis of SEC and SCC, and Lugol's solution staining technique was an effective auxiliary diagnostic measure, Lymph node metastasis was not found in patients with epithelial (EP) cancer, However, it was present in one (2.9%) of 34 patients with muscularis mucosal (MM) invasion, and in 5 (8.6%) of 58 patients with submucosal (SM) cancer, The 5-year survival rates of the patients with SEC and SCC were 75.5% and 71.4%, respectively (P > 0.05). The different depth of tumor invasion including EP, MM and SM cancers showed significant differences in the 5-year survival rate (P < 0.05), Although the prognosis for the patients with lymph node metastasis is poor, we should advocate extended lymph node dissection in surgical treatment of the patients in whom MM and SM cancers are suspected.展开更多
Objective:Considering that there are no effective biomarkers for the screening of cardia gastric cancer(CGC),we developed a noninvasive diagnostic approach,employing data-independent acquisition(DIA)proteomics to iden...Objective:Considering that there are no effective biomarkers for the screening of cardia gastric cancer(CGC),we developed a noninvasive diagnostic approach,employing data-independent acquisition(DIA)proteomics to identify candidate protein markers.Methods:Plasma samples were obtained from 40 subjects,10 each for CGC,cardia high-grade dysplasia(CHGD),cardia low-grade dysplasia(CLGD),and healthy controls.Proteomic profiles were obtained through liquid chromatography-mass spectrometry(LC-MS/MS-based DIA proteomics.Candidate plasma proteins were identified by weighted gene co-expression network analysis(WGCNA)combined with machine learning and further validated by the Human Protein Atlas(HPA)database.The area under the receiver operating characteristic curve(AUC)was used to evaluate the performance of the biomarker panel.Results:There was a clear distinction in proteomic features among CGC,CHGD,CLGD,and the healthy controls.According to the WGCNA,we found 42 positively associated and 164 inversely associated proteins related to CGC progression and demonstrated several canonical cancer-associated pathways.Combined with the results from random forests,LASSO regression,and immunohistochemical results from the HPA database,we identified three candidate proteins(GSTP1,CSRP1,and LY6G6F)that could together distinguish CLGD(AUC=0.91),CHGD(AUC=0.99)and CGC(AUC=0.98)from healthy controls with excellent accuracy.Conclusions:The panel of protein biomarkers showed promising diagnostic potential for CGC and precancerous lesions.Further validation and a larger-scale study are warranted to assess its potential clinical applications,suggesting a potential avenue for CGC prevention in the future.展开更多
基金Supported by National Natural Science Foundation of China,No.82273025China Postdoctoral Science Foundation,No.2022TQ0070 and No.2022M710759Shanghai Municipal Commission of Science and Technology,No.22JC1403003 and No.22S31903800.
文摘BACKGROUND Gastric subepithelial tumors(SETs)may harbor potential malignancy.Although it is well recognized that large SETs should be resected,the precise treatment strategy remains controversial.Compared to surgical resection,endoscopic resection(ER)has many advantages;however,ER of SETs in the cardia is challenging.AIM To evaluate the safety and efficacy of endoscopic full-thickness resection(EFTR)for the treatment of gastric cardia SETs.METHODS We retrospectively reviewed data from all patients with SETs originating from the muscularis propria layer in the gastric cardia that were treated by EFTR or submucosal tunneling ER(STER)at Zhongshan Hospital Fudan University between November 2014 and May 2022.Baseline characteristics and clinical outcomes,including procedure times and complications rates,were compared between groups of patients receiving EFTR and STER.RESULTS A total of 171 tumors were successfully removed[71(41.5%)tumors in the EFTR and 100(58.5%)tumors in the STER group].Gastrointestinal stromal tumors(GISTs)were the most common SET.The en bloc resection rate was 100%in the EFTR group vs 97.0%in STER group(P>0.05).Overall,the EFTR group had a higher complete resection rate than the STER group(98.6%vs 91.0%,P<0.05).The procedure time was also shorter in the EFTR group(44.63±28.66 min vs 53.36±27.34,P<0.05).The most common major complication in both groups was electrocoagulation syndrome.There was no significant difference in total complications between the two groups(21.1%vs 22.0%,P=0.89).CONCLUSION EFTR of gastric cardia SETs is a very promising method to facilitate complete resection with similar complications and reduced operative times compared to STER.In cases of suspected GISTs or an unclear diagnosis,EFTR should be recommended to ensure complete resection.
文摘The heterotopic pancreas, which is usually described as an untypical presence of pancreatic tissue without any anatomic or vascular continuity with the pancreas, is relatively rare. Clinical manifestations may include bleeding, inflammation, pain and obstruction; however, in most cases it remains silent and is diagnosed during autopsy. Here, we report a case of ectopic pancreatic lesion located in the gastric cardia. The patient was a 73-year-old woman who had a history (over four months) of chronic epigastric pain accompanied by heartburn. Esophagogastroduodenoscopy revealed inflammatory changes throughout the stomach and lower esophagus, as well as a flat polypoid mass with benign features located in the gastric cardia, approx. 10 mm below the “Z” line, measuring approx. 7 mm in diameter. Endoscopic biopsy forceps were used to remove the lesion. Histological examination of the lesion revealed the presence of heterotopic pancreatic tissue in the gastric mucosa. On the basis of the presented case, we suggest that pancreatic ectopia should be a part of differential diagnosis, not only when dealing with submucosal gastric lesions, but also with those that are small, flat and/or untypically located.
基金Supported by the National Key Clinical Specialist Construction Programs of China,No.2013-544Science and Technology Development Fund of Tianjin Education Commission for Higher Education,No.20130121Science Foundation of Tianjin Medical University,No.2016KYZM03
文摘AIM To evaluate the clinical and prognostic significance of preoperative and postoperative cytokeratin 19(CK19) and carcinoembryonic antigen(CEA) m RNA levels in peripheral blood of patients with gastric cardia cancer(GCC).METHODS We detected the preoperative and postoperative mR NA levels of CK19 and CEA in peripheral blood of 129 GCC patients by using reverse transcription-polymerase chain reaction and evaluated their clinical and prognostic significance by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard analysis. A new prognostic model which stratified patients into three different risk groups was established based on the independent prognostic factors.RESULTS Elevated preoperative and postoperative CK19 and CEA mR NA levels in peripheral blood of GCC patients were associated with lymph node metastasis. Univariate analysis showed that tumor size, histological grade, depth of tumor invasion, lymph node metastasis, preoperative CK19 m RNA, and preoperative and postoperative CEA m RNA levels were correlated with the prognosis of GCC patients. The multivariate analysis showed that lymph node status(P = 0.018), preoperative CK19(P = 0.035) and CEA(P = 0.011) m RNA levels were independent prognostic factors for overall survival(OS). The 5-year OS rates for the low-, intermediate-, and high-risk groups were 48.3%, 22.6%, and 4.6%, respectively(P < 0.001).CONCLUSION Elevated preoperative CK19 and CEA mR NA levels may be regarded as promising biomarkers for predicting lymph node metastasis and poor prognosis in patients with GCC. This new prognostic model may help us identify the subpopulations of GCC patients with the highest risk.
基金supported by grants from the National Natural Science Foundation of China(Grant No.81472323)Top Talent Support Project of Zhengzhou University(Grant No.ZDGD 13001)Innovation Scientists and Technicians Troop Construction Projects of Henan Province(Grant No.3047)
文摘Objective: This study aimed to determine if gastric cardia adenocarcinoma(GCA) risk was associated with the lys(A or *2) allele at the rs671(glu504lys) polymorphism within the aldehyde dehydrogenase 2(ALDH2) gene in a Chinese Han population. We also aimed to investigate ALDH2 genotypic distributions between subjects from high- and low-incidence areas for both GCA and esophageal squamous cell carcinoma(ESCC).Methods: We designed a case-control study including 2,686 patients with GCA and 3,675 control subjects from high- and lowincidence areas for both GCA and ESCC in China. Taq Man allele discrimination assay was used to genotype the rs671 polymorphism. χ~2 test and binary logistic regression analysis were used to estimate the odds ratios for the development of GCA,and multivariate ordinal logistic regression was used to analyze ALDH2 genotypic distributions among different groups.Results: Compared with ALDH2*1/*1 homozygotes, ALDH2*1/*2 and ALDH2*2/*2 carriers did not increase the risk for GCA in the Chinese Han population(P>0.05). Interestingly, the ratio of homozygous or heterozygous ALDH2 *2 carriers in highincidence areas for both GCA and ESCC was lower than that in low-incidence areas(P<0.001).Conclusions: Genotypes of rs671 at ALDH2 may not increase GCA susceptibility in Chinese Han populations. In addition, the ALDH2 genotypic distribution differs between Chinese Han populations from high- and low-incidence areas for both GCA and ESCC. Our findings may shed light on the possible genetic mechanism for the dramatic geographic differences of GCA occurrence in China.
基金Supported by the National Outstanding Young Scientist Award of China, No. 30025016State Key Project for Basic Research, No. G1998051206Foundation of Henan Education Committee 1999125 the US NIH Grant, No. CA65871
文摘AIM: To characterize the histochemical type and pattern of intestinal metaplasia (IM) adjacent to gastric cardia adenocarcinoma (GCA) and distal gastric cancer (GC) in Unzhou, Henan Province, China. METHODS: Alcian-blue-periodic acid Schiff and high iron diamine-Alcian blue histochemical methods were performed on 142 cases of IM, including 49 cases of GCA and 93 cases of GC. All the patients were from Linzhou, Henan Province, China, the highest incidence area for both GCA and squamous cell carcinoma. Radio- or chemotherapy was not applied to these patients before surgery. RESULTS: The detection rate of IM in tissues adjacent to GCA tissues was 44.9%, which was significantly lower than that in GC tissues (80.64%, P〈0.01). The rates of both incomplete small intestinal and colonic IM types identified by histochemistry in GCA tissues (31.82% and 63.64%, respectively) were significantly higher than those in GC (5.33% and 21.33%, respectively, P〈0.01). CONCLUSION: IM in GCA and GC should be considered as a separate entity. Further research is needed to evaluate whether neoplastic progression of IM is related to its mucin profile in GCA.
基金Supported by the Second University of Study of Naples
文摘AIM: To analyze retrospectively, our results about patients who underwent surgical treatment for adenocarcinoma of the cardia in relation to age, in order to evaluate surgical problems and prognostic factors. METHODS: From January 1987 to March 2003, 140 patients with adenocarcinoma of the cardia underwent resection in the authors' institution. They were divided into three groups with regard to age. Patients 〈70 and 〉 60 year old (31) were excluded; we also excluded 18 out of 109 patients with poor general status or systemic metastases. So, we compared 51 elderly (≥ 70 year old) and 58 younger patients (≤ 60 year old). The treatment was esophagectomy for type I tumors, and extended gastrectomy and distal esophagectomy for type Ⅱ and Ⅲ lesions. RESULTS: Laparotomy was carried out in 91 patients (83.4%), 38 in the elderly (74.5%) and 53 in younger patients (91.3%, P〈0.05). Primary resection was performed in 81 cases (89%) without significant differences between the two groups. Postoperative death was higher in the elderly (12.1%) than the other group (4.1%, P〈0.05), while morbidity was similar in both groups. A curative resection (R0) was performed in 59 patients (72.8%), 69.6% in the elderly and 75% in the younger group (P〉0.05). The overall 3- and 5-year survival rates were 26.7% and 17.8% respectively for the elderly and 40.7% and 35.1% respectively for younger patients (P = 0.1544). Survival rates were significantly associated with R0 resection, pathological node-poskive category and tumor differentiation in both groups.CONCLUSION: As the age of the general population increases, more elderly patients with gastric cardia cancer will be candidates for surgical resection. Age alone should not preclude surgical treatment in elderly patients with gastric cardia cancer and a tumor resection can be carried out safely. Certainly, we should take care in defining the surgical treatment in elderly patients, particularly as regarding the surgical approach; although the surgical approach does not influence the survival rate, the transhiatal way still remains the best one due, to the lower incidence of respiratory morbidity and thoracic pain.
基金National Natural Science Foundation of China,No.81872032No.U1804262National Key R&D Program of China,No.2016YFC0901403.
文摘BACKGROUND Gastric cardia adenocarcinoma(GCA),which has been classified as type II adenocarcinoma of the esophagogastric junction in western countries,is of similar geographic distribution with esophageal squamous cell carcinoma in China,and even referred as"sister cancer"by Chinese oncologists.The molecular mechanism for GCA is largely unknown.Recent studies have shown that decreased expression of E-cadherin is associated with the invasion and metastasis of multiple cancers.However,the E-cadherin expression has not been well characterized in gastric cardia carcinogenesis and its effect on GCA prognosis.AIM To characterize E-cadherin expression in normal gastric cardia mucosa,dysplasia and GCA tissues,and its influence on prognosis for GCA.METHODS A total of 4561 patients with GCA were enrolled from our previously established GCA and esophageal cancer databases.The enrollment criteria included radical surgery for GCA,but without any radio-or chemo-therapy before operation.The GCA tissue from 4561 patients and matched adjacent normal epithelial tissue(n=208)and dysplasia lesions(n=156)were collected,and processed as tissue microarray for immunohistochemistry.The clinicopathological characteristics were retrieved from the medical records in hospital and follow-up was carried out through letter,telephone or home interview.E-cadherin protein expression was determined by two step immunohistochemistry.Kaplan–Meier and Cox regression analyses were used to correlate E-cadherin protein expression with survival of GCA patients.RESULTS Of the 4561 GCA patients,there were 3607 males with a mean age of 61.6±8.8 and 954 females with a mean age of 61.9±8.6 years,respectively.With the lesions progressed from normal gastric cardia mucosa to dysplasia and GCA,the positive immunostaining rates for E-cadherin decreased significantly from 100%to 93.0%and 84.1%,respectively(R2=0.9948).Furthermore,E-cadherin positive immunostaining rate was significantly higher in patients at early stage(0 and I)than in those at late stage(II and III)(92.7%vs 83.7%,P=0.001).E-cadherin positive expression rate was significantly associated with degree of differentiation(P=0.001)and invasion depth(P<0.001).Multivariate analysis showed that the GCA patients with positive E-cadherin immunostaining had better survival than those with negative(P=0.026).It was noteworthy that E-cadherin positive expression rate was similar in patients with positive and negative lymph node metastasis.However,in patients with negative lymph node metastasis,those with positive expression of E-cadherin had better survival than those with negative expression(P=0.036).Similarly,in patients with late stage GCA,those with positive expression of E-cadherin had better survival than those with negative expression(P=0.011).CONCLUSION E-cadherin expression may be involved in gastric cardia carcinogenesis and low expression of E-cadherin may be a promising early biomarker and overall survival predictor for GCA.
文摘The factors associated with an increase in gastric cardia adenocarcinoma are poorly understood.Environmental factors such as Helicobacter pylori(H.pylori) infection and diet have been hypothesized to play a role in the recently increased risk of this disease,but additional studies are needed.In conducting studies to establish the relationship between potential risk factors and gastric cardia adenocarcinoma,it is necessary to carefully consider the role of bias.In a recently published study,the reported associations between H.pylori as well as post-meal physical exertion and gastric cardia adenocarcinoma may have been greatly influenced by selection bias.
基金supported in part by National Natural Science Foundation of China(No.81101889)
文摘Objective: To investigate the association between gastric cardia adenocarcinoma (GCA) and ten functional single nueleotide polymorphisms (SNPs), including TPY3BPI rs560191 G〉C, CASP8 rs1035142 G〉T, CASP7 rs3127075 G〉C, CASP7 rs7907519 C〉A, and six C1 orf 10/CRNN variants. We performed a hospital- based case-control study to evaluate the genetic effects of these SNPs. Methods: Two hundred and forty-three GCA cases and 476 controls were enrolled in this study. A custom- by-design 48-Plex SNPscanTM Kit was used to determine their genotypes. Results: When the TP^3BP1 rs560191 GG homozygote genotype was used as the reference group, the GC genotype was associated with a significantly increased risk of GCA. The CC genotype was not associated with the risk of GCA compared with the GG genotype. None of the CASP8 rs1035142 G〉T, CASP7 rs3127075 G〉C, CASP7 rs7907519 C〉A or the six ClorflO/CRNN polymorphisms showed a significant difference in genotype distributions between the cases and the controls. Conciusions: The results demonstrated that the functional polymorphism TP53BPI rs560191 G〉C might contribute to GCA susceptibility. However, the statistical power of our study was limited. Large, well- designed studies and further functional investigations are needed to confirm our findings.
文摘OBJECTIVE: To determine the value of resection of combined visceral organs in surgical treatment of gastric cardiac carcinoma. METHODS: We retrospectively analyzed 217 random patients with carcinoma of the gastric cardia who underwent a gastric cardiac resection. The patients had been treated as follows: 186 with partial gastrectomy, 31 with total gastrectomy, 97 with a combined-visceral resection, of which 82 underwent a splenectomy plus partial pancreatectomy, 10 with splenectomy alone and 5 with partial hepatectomy and diaphragmatectomy. RESULTS: The total patients were divided into 3 groups: 128 with a gastrectomy alone, 10 with gastrectomy and splenectomy, and 82 with gastrectomy and splenectomy plus pancreatectomy. The operating times for these 3 groups were respectively 3.0 h, 3.1 h and 3.8 h. The hospitalization times were respectively 23.8 d, 31.2 d and 25.9 d. No differences in post-operative complications were found between these 3 groups. There were 92 patients who underwent a gastrectomy combined with a splenectomy and (or) the pancreatectomy, in which 92 No.10 lymph nodes were eliminated, with an average of one in each patient. Among the 125 patients not receiving a splenectomy but with elimination of lymph nodes, 82 underwent a gastrectomy combined with partial pancreatectomy, of which 107 lymph nodes were eliminated for the No. 11 group, with an average of 1.3 in each patient. There was a statistically significant difference between the 2 groups. The overall survival rates were similar in the 3 groups showing no statistical differences, but was higher in the Stage Ⅲ patients with a combined resection of multi-organs. For patients in the Stage Ⅳ without resection of multi-organs, the survival rate was higher, but there was no significant difference between the 2 groups. CONCLUSION: It is difficult to determine precisely the involvement of para-tumorous organs with the eye during an operation. Combining a splenectomy with a pancreatectomy does not increase the post-operative complications following surgical treatment for carcinoma of the gastric cardia. The combination of a splenectomy and partial pancreatectomy results in a higher survival rate and has an important significance for eliminating the lymph nodes of group 10 and 11, especially for patients in Stage Ⅲ. In the application of a resection combining multi-organs, the doctor should make every effort to decrease the trauma and the complications based on the condition that the cancerous tissue is totally resected.
文摘AIM:To investigate the relationship between human papillomavirus (HPV) infection and concurrent esophagus and gastric cardia cancer from the same patient (CC) and examine the significance of P16 INK4A protein expression.METHODS:Polymerase chain reaction was used to detect the presence of HPV type16 (HPV16).The expression of P16 INK4A protein was detected using immunohistochemistry.RESULTS:Among the CC specimens,HPV16-DNA was found in eight cases of esophageal squamous cell carcinoma (ESCC) and five cases of gastric cardia adenocarcinoma (GCA),respectively (47% vs 29%),and two of both ESCC and GCA.P16 INK4A was highly expressed in both ESCC and GCA.In the HPV-associated positive CC,higher P16 INK4A expression was observed in the GCA than in the ESCC (75% vs 25%,P < 0.05).CONCLUSION:HPV16 as a correlated risk factor may play an important role in the development of ESCC and GCA.P16 INK4A may be a screening index in the HPVassociated carcinoma of gastric cardia.
文摘Gastric gastrointestinal stromal tumor (GIST), esophageal squamous cell carcinoma and gastric cardia adenocarcinoma are distinct neoplasms originating from different cell layers; therefore, simultaneous development of such carcinomas is relatively rare. Auxiliary examinations revealed coexistence of esophageal and gastric cardia carcinoma with lymph node metastasis in a 77-year-old man. Intraoperatively, an extraluminal tumor (about 6.0 cm × 5.0 cm × 6.0 cm) at the posterior wall of the gastric body, a tumor (about 2.5 cm × 2.0 cm) in the lower esophagus, and an infiltrative and stenosing tumor (about 1.0 cm × 2.0 cm) in the gastric cardia were detected. Wedge resection for extraluminal gastric tumor, radical esophagectomy for lower esophageal tumor, and cardiac resection with gastroesophageal (supra-aortic arch anastomoses) were performed. Postoperative histological examination showed synchronous occurrence of gastric GIST, esophageal squamous cell carcinoma, and gastric cardia adenocarcinoma. Furthermore, immunohistochemistry indicated strong staining for c-Kit/CD117, Dog-1, Ki-67 and smooth muscle, while expression of S-100 and CD34 was negative.
文摘Background In China, esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) share susceptibility loci, but different rates of multiple primary cancer and male/female ratio suggest the proportion of familial cancer is not equal. Methods The percent of cases with a positive family history, median onset age, rate of multiple primary cancer, and male/female ratio associated with upper, middle, lower third ESCC and GCA were compared to reveal the proportion of familial cancer. The 7267 subjects analyzed constituted all ESCC and GCA cases in whom the cancer was resected with cure intention between 1970 and 1994 at the 4th Hospital of Hebei Medical University. Results A positive family history for cancer was most often associated with the multiple primary ESCC and/or GCA cases, e.g. with 42% of the males and 59% of the females. For upper, middle, lower third ESCC and GCA, the percent of cases with a positive family history decreased by 38.5%, 26.3%, 26.5%, and 11.2% in males (P 〈0.000) and 25.0%, 22.3%, 23.9%, and 9.8% in females (P 〈0.0001). Median onset age increased from 49, 52, 55, to 56 years old in males and from 50, 53, 55, to 56 years old in females ( both P 〈0.0001) for upper, middle, lower third ESCC and GCA. Male/female ratio increased from 2.2, 2.1, 2.2, to 6.2:1 for upper, middle, lower third ESCC and GCA (P〈0.0001). For upper, middle, lower third ESCC and GCA, the percent of multiple primary cancers decreased from 21.2%, 2.3%, 2.2%, to 1.5% in males and from 14.3%, 2.4%, 3.4%, to 3.1% in females. The preponderance of males, smoking, drinking, or onset-age 〉50 years was significantly higher in GCA than in ESCC, and the difference in the rates of multiple primary cancers between the preponderant and the non-preponderant cases was significant in GCA, but not in ESCC, suggesting non-equal requirement for genetic susceptibility when environmental hazards did not exist. Conclusions The proportion of familial cancer in upper gastrointestinal carcinomas decreases by the priamry site of upper, middle, lower third esophagus and gastric cardia. Considering familial and sporadic cancers differ in preventability, screening strategy and recurrence, our findings have basic and clinical implications.
文摘Background Gastroesophageal junction adenocarcinomas include adenocarcinomas of the distal esophagus (DE) and gastric cardia (GC). It is controversial whether these tumors are the same entity and whether they have the same survival rates. Patients with DE and GC adenocarcinomas have a similar survival rate in the US; however, data are lacking in Asian countries. Therefore, we conducted a retrospective study to understand the implications of the tumor location in the survival of Asian patients. Methods A total of 209 patients with pathologically confirmed DE and GC adenocarcinomas, from 2005 to 2007, were included in the study. We identified patients with adenocarcinomas of the DE (DE group, n=91) and GC (GC group) (n=118), We performed an unadjusted survival analysis using the Kaplan-Meier method, and used a Cox proportional hazards regression model to adjust for potential confounding covariates. Results We found no significant difference between the overall survival of the DE and GC groups. The 3-year survival rates were 44.8% and 53.0%, respectively, and the 5-year survival rates were 27.9% and 30.2%, respectively (P=0.162). We found no significant difference in early staging, advanced staging, different T staging, and different N staging, between the groups. Both advanced post-operative N staging and advanced AJCC staging had a significant adverse effect on survival. Conclusions Patients with DE and GC adenocarcinomas have similar survival rates in the Asian population. Both post-operative N staging and AJCC staging are prognostic factors.
文摘From January 1970 to June 1999, 141 patients with superficial esophageal and cardiac carcinomas (SEC and SCC) underwent surgical treatment, Of the 141 patients 128 (90.8%) had slight symptoms related to swallowing, and the remaining 13 (9.2%) were asymptomatic, Balloon cytology and esophagoscopy proved very useful for the diagnosis of SEC and SCC, and Lugol's solution staining technique was an effective auxiliary diagnostic measure, Lymph node metastasis was not found in patients with epithelial (EP) cancer, However, it was present in one (2.9%) of 34 patients with muscularis mucosal (MM) invasion, and in 5 (8.6%) of 58 patients with submucosal (SM) cancer, The 5-year survival rates of the patients with SEC and SCC were 75.5% and 71.4%, respectively (P > 0.05). The different depth of tumor invasion including EP, MM and SM cancers showed significant differences in the 5-year survival rate (P < 0.05), Although the prognosis for the patients with lymph node metastasis is poor, we should advocate extended lymph node dissection in surgical treatment of the patients in whom MM and SM cancers are suspected.
基金supported by grants from the Beijing Nova Program(grant number:Z201100006820069)the Hope Star Talent Incentive Program of the Cancer Hospital of Chinese Academy of Medical Sci-ences,the National Natural Science Fund(grant number:81573224)+1 种基金the CAMS Innovation Fund for Medical Sciences(grant number:2021-I2M-1-023)the Shandong Province Natural Science Foundation Youth Branch(grant number:ZR202211080124).
文摘Objective:Considering that there are no effective biomarkers for the screening of cardia gastric cancer(CGC),we developed a noninvasive diagnostic approach,employing data-independent acquisition(DIA)proteomics to identify candidate protein markers.Methods:Plasma samples were obtained from 40 subjects,10 each for CGC,cardia high-grade dysplasia(CHGD),cardia low-grade dysplasia(CLGD),and healthy controls.Proteomic profiles were obtained through liquid chromatography-mass spectrometry(LC-MS/MS-based DIA proteomics.Candidate plasma proteins were identified by weighted gene co-expression network analysis(WGCNA)combined with machine learning and further validated by the Human Protein Atlas(HPA)database.The area under the receiver operating characteristic curve(AUC)was used to evaluate the performance of the biomarker panel.Results:There was a clear distinction in proteomic features among CGC,CHGD,CLGD,and the healthy controls.According to the WGCNA,we found 42 positively associated and 164 inversely associated proteins related to CGC progression and demonstrated several canonical cancer-associated pathways.Combined with the results from random forests,LASSO regression,and immunohistochemical results from the HPA database,we identified three candidate proteins(GSTP1,CSRP1,and LY6G6F)that could together distinguish CLGD(AUC=0.91),CHGD(AUC=0.99)and CGC(AUC=0.98)from healthy controls with excellent accuracy.Conclusions:The panel of protein biomarkers showed promising diagnostic potential for CGC and precancerous lesions.Further validation and a larger-scale study are warranted to assess its potential clinical applications,suggesting a potential avenue for CGC prevention in the future.