Search

Given that esophageal cancer is highly malignant, the discovery of novel prognostic markers is eagerly awaited. We performed serological identification of antigens by recombinant cDNA expression cloning (SEREX) and identified SKI proto‐oncogene protein and transmembrane p24 trafficking protein 5 (TMED5) as antigens recognized by serum IgG antibodies in patients with esophageal carcinoma. SKI and TMED5 proteins were expressed in Escherichia coli, purified by affinity chromatography, and used as antigens. The serum anti‐SKI antibody (s‐SKI‐Ab) and anti‐TMED5 antibody (s‐TMED5‐Ab) levels were significantly higher in 192 patients with esophageal carcinoma than in 96 healthy donors. The presence of s‐SKI‐Abs and s‐TMED5‐Abs in the patients' sera was confirmed by western blotting. Immunohistochemical staining showed that the TMED5 protein was highly expressed in the cytoplasm and nuclear compartments of the esophageal squamous cell carcinoma tissues, whereas the SKI protein was localized predominantly in the nuclei. Regarding the overall survival in 91 patients who underwent radical surgery, the s‐SKI‐Ab‐positive and s‐TMED5‐Ab‐negative statuses were significantly associated with a favorable prognosis. Additionally, the combination of s‐SKI‐Ab‐positive and s‐TMED5‐Ab‐negative cases showed an even clearer difference in overall survival as compared with that of s‐SKI‐Ab‐negative and s‐TMED5‐Ab‐positive cases. The s‐SKI‐Ab and s‐TMED5‐Ab biomarkers are useful for diagnosing esophageal carcinoma and distinguishing between favorable and poor prognoses. [ABSTRACT FROM AUTHOR]

The relationship between energy production and cancer is attracting attention. This study aimed to investigate the clinicopathological significance of fumarate hydratase (FH), a tricarboxylic acid cycle enzyme, in gastric cancer using autoantibodies as biomarkers. The study analyzed 116 patients who underwent gastric cancer surgery and 96 healthy controls. Preoperative serum FH autoantibody (s-FH-Ab) titers were analyzed using an immunosorbent assay with an amplified luminescent proximity homogeneous assay. Receiver operating characteristic analysis was used to determine the cutoff s-FH-Ab titer. Clinicopathological factors and prognosis were compared between the high and low s-FH-Ab groups. The s-FH-Ab levels were significantly higher in the gastric cancer group than in the control group (p = 0.01). Levels were elevated even in patients with stage I gastric cancer compared with healthy controls (p = 0.02). A low s-FH-Ab level was significantly associated with distant metastasis (p = 0.01), peritoneal dissemination (p < 0.05), and poor overall survival (p < 0.01). Multivariate analysis revealed that low s-FH-Ab levels were an independent risk factor for poor prognosis (p < 0.01). Therefore, s-FH-Ab levels may be a useful biomarker for early diagnosis and the prediction of prognosis in patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Inflammation is closely associated with cerebrovascular diseases, cardiovascular diseases, diabetes, and cancers, and it is accompanied by the development of autoantibodies in the early stage of inflammation-related diseases. Hence, it is meaningful to discover novel antibody biomarkers targeting inflammation-related diseases. In this study, Jumonji C-domain-containing 6 (JMJD6) was identified by the serological identification of antigens through recombinant cDNA expression cloning. In particular, JMJD6 is an antigen recognized in serum IgG from patients with unstable angina pectoris (a cardiovascular disease). Then, the serum antibody levels were examined using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay and a purified recombinant JMJD6 protein as an antigen. We observed elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with inflammation-related diseases such as ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers (including esophageal cancer, EC; gastric cancer; lung cancer; and mammary cancer), compared with the levels in healthy donors. The s-JMJD6-Ab levels were closely associated with some inflammation indicators, such as C-reactive protein and intima–media thickness (an atherosclerosis index). A better postoperative survival status of patients with EC was observed in the JMJD6-Ab-positive group than in the negative group. An immunohistochemical analysis showed that JMJD6 was highly expressed in the inflamed mucosa of esophageal tissues, esophageal carcinoma tissues, and atherosclerotic plaques. Hence, JMJD6 autoantibodies may reflect inflammation, thereby serving as a potential biomarker for diagnosing specific inflammation-related diseases, including stroke, AMI, DM, and cancers, and for prediction of the prognosis in patients with EC. [ABSTRACT FROM AUTHOR]

Background Previous studies have evaluated the clinicopathological significance of carcinoembryonic antigen (CEA) of esophageal cancer in relatively small numbers of patients. Therefore, this study aimed to clarify the prognostic significance of CEA in 1822 patients with esophageal squamous cell carcinoma (SCC). Methods Based on the Japanese Esophageal Society nationwide multi-institutional retrospective study, a total of 1,748 surgically treated ESCC from 15 hospitals were enrolled to evaluate prognostic impact of preoperative CEA values. Among them, 605 patients were categorized to up-front surgery group, and 1,217 patients were categorized to neoadjuvant therapy group. The CEA threshold for positivity was 3.7 ng/ml. The clinicopathological and prognostic impact of CEA was evaluated by univariate and multivariate analysis in each treatment modality groups. Results In total, the CEA positive rate was 25.8% (470/1822). CEA-positive status was significantly associated with distant metastasis (P  = 0.004) but not associated with other factors. CEA-positive status was associated with poor overall survival (P  < 0.001) in univariate analysis as well as multivariate analysis (P  = 0.003). Conclusions CEA was an independent prognostic determinant of overall survival in esophageal SCC. Based on the subgroup analysis, regardless of the treatment modality, patients with high pretreatment CEA showed poor overall survival. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to compare the efficacy of taxane‐based and platinum‐based regimens in patients with early recurrent gastric cancer after radical surgery with S‐1 adjuvant chemotherapy. Methods: The medical records of 118 patients from six institutes with early recurrent stage II/III gastric cancer, who developed recurrence during adjuvant S‐1 or within 6 months after completion of adjuvant therapy between January 2006 and December 2017, were retrospectively analyzed. Patients treated with second line chemotherapy were enrolled and followed to the end of December 2019. The impact of two regimens, taxane‐based (n = 46) versus platinum‐based (n = 31), on treatment outcome were evaluated using multivariate analysis. Results: Median overall survival was 9.0 months and median progression‐free survival was 4.1 months. No difference was observed in overall survival between taxane‐based and platinum‐based regimens (P = 0.64). Although not significant, the response rate of platinum‐based regimens was better than that of taxane‐based regimens (16% vs. 6.5%, P = 0.26). Multivariate analysis identified performance status (P = 0.040), multiorgan metastases (P = 0.029), and undifferentiated histological type (P = 0.018) as independent poor prognostic factors. In undifferentiated histological type, multiorgan metastases (P = 0.013) and taxane‐based regimens (P = 0.018) were independent prognosis factors characterized by multivariate analysis. Conversion rate to third‐line chemotherapy or more was 51% in undifferentiated histological type and 65% in differentiated histological type (P = 0.26). Conclusion: Platinum‐based regimens may be recommended for undifferentiated early recurrent gastric cancer after S‐1 adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

The sensitivity and specificity of a new automated electrochemiluminescence immunoassay system, Elecsys® Anti-p53 (Elecsys), were compared with that of the conventional serum anti-p53 antibody (s-p53-Ab) enzyme-linked immunosorbent assay kit [MESACUP anti-p53 test (MESACUP)]. Elecsys and MESACUP were used to analyze the levels of s-p53-Abs in patients with esophageal, colorectal and breast cancer. A total of 532 controls and 288, 235 and 329 patients with esophageal, colorectal and breast cancer, respectively, were enrolled. Additionally, the sera of patients with benign diseases of the esophagus, colorectal system and breast, patients with autoimmune diseases and healthy volunteers were analyzed as controls. Sensitivity and specificity were compared between the two assay systems. Positive agreement rates were 58.7% in all samples, 71.2% in esophageal samples, 73.6% in colorectal samples and 35.1% in breast samples. Negative agreement rates for the different cancer types were ≥97.1% and the overall agreement rates were ≥92.3%. When the specificities of the two assays were aligned for all samples, Elecsys demonstrated higher sensitivities for all types of analyzed cancer together, as well as for esophageal, colorectal and breast cancer, respectively. Although positive concordance between the two assay systems was low in terms of specificity, Elecsys had a higher sensitivity than the MESACUP. [ABSTRACT FROM AUTHOR]

Solid cancers have a poor prognosis, and their morbidity and mortality after surgery is high. Even after radical surgery for esophageal cancer, there have been cases of early postoperative death. The present study therefore aimed to explore new tumor markers that can predict the early postoperative prognosis. To identify antibody markers, serological antigens were identified using recombinant cDNA expression cloning (SEREX). The results identified striatin 4 (STRN4) as the antigen recognized by serum IgG antibodies in patients with esophageal cancer. After performing an amplified luminescence proximity homogeneous assay-linked immunosorbent assay (AlphaLISA), it was revealed that when compared with healthy donors, serum anti-STRN4 antibody (STRN4-Ab) levels were significantly higher not only in patients with esophageal cancer but also to lesser extent, in those with gastric cancer, colorectal cancer, lung cancer and breast cancer. Compared with STRN4-Ab-negative patients with esophageal cancer, STRN4-Ab-positive patients had a poorer postoperative prognosis at early stages, suggesting that STRN4-Abs may be useful for predicting poor early-stage prognoses of patients with esophageal cancer. The positive diagnosis rates of esophageal cancer using the STRN4-Ab marker and conventional markers, including squamous cell carcinoma antigen and p53 antibody alone, were 26.4, 35.2 and 19.1% respectively; a result that increased up to 59.1% by combining all three markers. Serum STRN4-Ab may serve as a novel marker of esophageal cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND Although recurrence after surgery for esophagogastric junction (EGJ) adenocarcinoma frequently develops in the mediastinal and para-aortic lymph nodes (LN), distant LN recurrence in the mesocolon is rare. We report a rare case of ileocecal LN metastasis in the ascending mesocolon after radical surgery for an EGJ adenocarcinoma. CASE REPORT We performed subtotal esophagectomy with mediastinal and para-gastric LN dissection in a patient with an advanced EGJ adenocarcinoma. Clinicopathologically, the patient was diagnosed with type I EGJ adenocarcinoma based on Siewert's classification (pathological T3N1M0). One year after surgery, computed tomography showed enlarged lymph nodes around the ileocolic artery, and further examination was performed. Although positron emission tomography-computed tomography showed that the lesion had moderate uptake of fluorodeoxyglucose, we did not find the reason for the enlarged lymph nodes. Finally, laparoscopic ileocecal resection was performed for diagnostic and therapeutic purposes. Clinicopathological tests revealed that the specimen was a moderately differentiated adenocarcinoma, which was strongly suspected to be a metastasis of the EGJ adenocarcinoma. CONCLUSIONS We encountered a rare case of EGJ adenocarcinoma that spread to the ileocecal LN in the ascending mesocolon. To the best of our knowledge, this is the first such report in the literature to date. Laparoscopic ileocecal resection for metastasis to the ascending mesocolon seems reasonable as a local control.

Numerous antibody biomarkers have been reported for cancer and atherosclerosis-related diseases. The major complications of atherosclerosis and diabetes mellitus (DM) are acute ischemic stroke (AIS), cardiovascular disease (CVD) and chronic kidney disease (CKD). Cancer development is accompanied by arterial disorders, such as angiogenesis and atherosclerosis, and DM is a risk factor for the development of certain types of cancer. Atherosclerosis-related diseases and cancers are therefore interrelated and could be detected using a common biomarker. In the present study, the initial screening using the protein array method identified KIAA0513 as an antigen recognized by serum IgG antibodies in patients with atherosclerosis. The amplified luminescent proximity homogeneous assay-linked immunosorbent assay revealed significantly higher serum antibody levels against recombinant KIAA0513 protein in patients with AIS, transient ischemic attack (TIA), DM, CVD, obstructive sleep apnea syndrome (OSAS), CKD and solid cancers, such as esophageal, gastric, colon, lung and breast cancers, compared with healthy donors. A receiver operating characteristic (ROC) analysis revealed that the highest areas under the ROC curves of anti-KIAA0513 antibodies were obtained for esophageal cancer, nephrosclerosis-type CKD and DM. Spearman's correlation analysis revealed that serum anti-KIAA0513 antibody levels were associated with maximum intima-media thickness and plaque score, which are indices of atherosclerosis and stenosis. Serum anti-KIAA0513 antibody markers appear to be useful for diagnosing AIS, TIA, DM, CVD, OSAS, CKD and solid cancers, and may reflect common arterial alterations leading to atherosclerotic and cancerous diseases., Competing Interests: The present study was performed in collaboration with Fujikura Kasei Co., Ltd. GT is an employee of Fujikura Kasei Co., Ltd. The other authors have no competing interests., (Copyright: © 2024 Hiwasa et al.)

Objectives The current carbohydrate antigen 125 (CA125) cutoff value demonstrated high specificity but low sensitivity. Therefore, we used new cutoff values to evaluate the clinical impact of perioperative CA125 in gastric cancer. Methods This study retrospectively analyzed 525 patients with gastric cancer (349 males and 176 females), of whom 445 patients underwent R0 resection and 80 patients underwent R1/R2 resection between 2011 and 2020. The receiver operating characteristic curve indicated preoperative and postoperative cutoff CA125 values of 15.7 IU/mL and 17.3 IU/mL, respectively, to predict overall survival. Furthermore, we analyzed changes in postoperative CA125 levels and evaluated their prognostic impact using multivariate analysis. Results The preoperative CA125-positive rate was 25%. Males, advanced TNM factors, and noncurative resection cases demonstrated significantly higher positive rates than the other group. The preoperative CA125-positive group exhibited a significantly higher noncurative resection rate than the preoperative CA125-negative group (32% versus 10%, P < 0.01). Preoperatively, CA125-positive status was an independent poor prognostic factor (P < 0.01), and at three months postoperatively, it tended to be a poor prognostic factor. Conclusions High preoperative CA125 (>15.7 IU/mL) was a significant predictor for noncurative resection and poor overall prognosis in gastric cancer. Furthermore, postoperative CA125-positive status three months postoperatively was also a potential predictor of recurrence and poor prognosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of Toho University Omori Medical Center (Tokyo, Japan) issued approval M20196 19056 18002. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Moriyama et al.)

Purpose: This study aimed to determine the clinicopathologic and prognostic significance of squamous cell carcinoma antigen (SCC-Ag) in patients with esophageal SCC who underwent radical surgery without neoadjuvant therapy., Methods: This study included 566 patients with primary esophageal SCC who underwent radical resection without neoadjuvant therapy at 15 Japanese hospitals between 2008 and 2016. The cutoff value of SCC-Ag was 1.5 ng/mL based on the receiver operating characteristic curves. Preoperative SCC-Ag and postoperative SCC-Ag were analyzed to evaluate clinicopathological and prognostic significance. Survival curves were compared between the SCC-Ag-positive group and the SCC-Ag-negative group. The prognostic impact of SCC-Ag was evaluated using univariate and multivariate analyses., Results: The preoperative SCC-Ag-positive rate was 23.5% (133/566). SCC-Ag-positive status was significantly associated with old age (p = 0.042), tumor depth (p <0.001), and tumor stages (p <0.001). The preoperative SCC-Ag-positive group had significantly poorer overall survival than the SCC-Ag-negative group (p = 0.030), but it was not an independent predictor of poor prognosis. Postoperative SCC-Ag-positive status was an independent risk factor for poor overall survival (p = 0.034)., Conclusion: Both pre- and postoperative SCC-Ag-positive statuses were significantly associated with poor prognosis. Postoperative SCC-Ag-positive status was an independent risk factor for predicting overall survival.

Aim: This study aimed to compare the efficacy of taxane-based and platinum-based regimens in patients with early recurrent gastric cancer after radical surgery with S-1 adjuvant chemotherapy., Methods: The medical records of 118 patients from six institutes with early recurrent stage II/III gastric cancer, who developed recurrence during adjuvant S-1 or within 6 months after completion of adjuvant therapy between January 2006 and December 2017, were retrospectively analyzed. Patients treated with second line chemotherapy were enrolled and followed to the end of December 2019. The impact of two regimens, taxane-based (n = 46) versus platinum-based (n = 31), on treatment outcome were evaluated using multivariate analysis., Results: Median overall survival was 9.0 months and median progression-free survival was 4.1 months. No difference was observed in overall survival between taxane-based and platinum-based regimens (P = 0.64). Although not significant, the response rate of platinum-based regimens was better than that of taxane-based regimens (16% vs. 6.5%, P = 0.26). Multivariate analysis identified performance status (P = 0.040), multiorgan metastases (P = 0.029), and undifferentiated histological type (P = 0.018) as independent poor prognostic factors. In undifferentiated histological type, multiorgan metastases (P = 0.013) and taxane-based regimens (P = 0.018) were independent prognosis factors characterized by multivariate analysis. Conversion rate to third-line chemotherapy or more was 51% in undifferentiated histological type and 65% in differentiated histological type (P = 0.26)., Conclusion: Platinum-based regimens may be recommended for undifferentiated early recurrent gastric cancer after S-1 adjuvant chemotherapy., (© 2021 John Wiley & Sons Australia, Ltd.)

The sensitivity and specificity of a new automated electrochemiluminescence immunoassay system, Elecsys ® Anti-p53 (Elecsys), were compared with that of the conventional serum anti-p53 antibody (s-p53-Ab) enzyme-linked immunosorbent assay kit [MESACUP anti-p53 test (MESACUP)]. Elecsys and MESACUP were used to analyze the levels of s-p53-Abs in patients with esophageal, colorectal and breast cancer. A total of 532 controls and 288, 235 and 329 patients with esophageal, colorectal and breast cancer, respectively, were enrolled. Additionally, the sera of patients with benign diseases of the esophagus, colorectal system and breast, patients with autoimmune diseases and healthy volunteers were analyzed as controls. Sensitivity and specificity were compared between the two assay systems. Positive agreement rates were 58.7% in all samples, 71.2% in esophageal samples, 73.6% in colorectal samples and 35.1% in breast samples. Negative agreement rates for the different cancer types were ≥97.1% and the overall agreement rates were ≥92.3%. When the specificities of the two assays were aligned for all samples, Elecsys demonstrated higher sensitivities for all types of analyzed cancer together, as well as for esophageal, colorectal and breast cancer, respectively. Although positive concordance between the two assay systems was low in terms of specificity, Elecsys had a higher sensitivity than the MESACUP., Competing Interests: HSh received research funding from Ono Pharmaceutical, Taiho Pharmaceutical and Roche Diagnostics K.K. HSu was an employee of Roche Diagnostics K.K. ME is an employee of Roche Diagnostics GmbH. The Elecsys assay system is manufactured by Roche Diagnostics K. K., (Copyright: © Suzuki et al.)

Purpose: Hypercalcemia has been reported as a poor prognostic factor in malignant tumors. However, no report has shown the clinical impact of serum calcium levels on patients with esophageal cancer. We evaluated the prognostic impact of preoperative serum calcium levels on patients with esophageal cancer., Methods: We evaluated 240 patients (197 men, 43 women; mean age, 66 years; age range, 34-85 years) with esophageal cancer who underwent radical surgery between September 2008 and December 2017. After assigning the patients to two groups (high calcium group, 8.8 mg/dL or more and low calcium group, 8.7 mg/dL or less), we compared the groups' overall survival and the clinicopathological features. The clinicopathological and prognostic significance of preoperative serum calcium levels were evaluated in a univariate and multivariate analysis., Results: The patients with deep tumors showed low serum calcium levels significantly more frequently (P <0.05). The low calcium group showed a significantly worse prognosis than the high calcium group (P <0.05). However, low serum calcium level was not an independent poor prognostic factor., Conclusions: Preoperative low serum calcium levels were associated with advanced tumors. Low serum calcium might be associated with esophageal cancer progression.