ATM mutations as an independent prognostic factor and potential biomarker for immune checkpoint therapy in endometrial cancer

Abstract Background Gastric cancer (GC) is a malignancy with high morbidity/mortality, partly due to a lack of reliable biomarkers for early diagnosis. It is important to develop reliable biomarker(s) with specificity, sensitivity and convenience for early diagnosis. The role of tumour-associated macrophages (TAMs) and survival of GC patients are controversial. Macrophage colony stimulating factor (MCSF) regulates monocytes/macrophages. Elevated MCSF is correlated with invasion, metastasis and poor survival of tumour patients. IL-34, a ligand of the MCSF receptor, acts as a “twin” to MCSF, demonstrating overlapping and complimentary actions. IL-34 involvement in tumours is controversial, possibly due to the levels of MCSF receptors. While the IL34/MCSF/MCSFR axis is very important for regulating macrophage differentiation, the specific interplay between these cytokines, macrophages and tumour development is unclear.Methods A multi-factorial evaluation could provide more objective utility, particularly for either prediction and/or prognosis of gastric cancer. Precision medicine requires molecular diagnosis to determine the specifically mutant function of tumours, and is becoming popular in the treatment of malignancy. Therefore, elucidating specific molecular signalling pathways in specific cancers facilitates the success of a precision medicine approach. Gastric cancer tissue arrays were generated from stomach samples with TNM stage, invasion depth and the demography of these patients (n = 185). Using immunohistochemistry/histopathology, MCSF, IL-34 and macrophages were determined.Results We found that IL-34 may serve as a predictive biomarker, but not as an independent, prognostic factor in GC; MCSF inversely correlated with survival of GC in TNM III‑IV subtypes. Increased CD68+TAMs were a good prognostic factor in some cases and could be used as an independent prognostic factor in male T3 stage GC.Conclusion Our data support the potency of IL-34, MCSF, TAMs and the combination of IL34/TAMs as novel biological markers for GC, and may provide new insight for both diagnosis and cellular therapy of GC.

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Transection of vaginal cuff is an independent prognostic factor in stage I endometrial cancer

European Journal of Surgical Oncology ◽

10.1016/j.ejso.2007.07.199 ◽

2008 ◽

Vol 34 (2) ◽

pp. 241-246 ◽

Cited By ~ 4

Author(s):

H. Arndt-Miercke ◽

A. Martin ◽

V. Briese ◽

R. Fietkau ◽

B. Gerber ◽

...

Keyword(s):

Endometrial Cancer ◽

Prognostic Factor ◽

Independent Prognostic Factor ◽

Stage I ◽

Vaginal Cuff

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Analysis of Patients With Stage IIIC Endometrial Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000154 ◽

2014 ◽

Vol 24 (6) ◽

pp. 1033-1041 ◽

Cited By ~ 9

Author(s):

Taner Turan ◽

Isin Ureyen ◽

Ipek Duzguner ◽

Enis Ozkaya ◽

Tolga Tasci ◽

...

Keyword(s):

Endometrial Cancer ◽

Prognostic Factor ◽

Lymph Nodes ◽

Univariate Analysis ◽

Independent Prognostic Factor ◽

Stage Iiic ◽

Metastatic Lymph Nodes ◽

Systematic Lymphadenectomy ◽

Metastatic Lymph ◽

Gynecology And Obstetrics

ObjectiveWe aimed to define the factors that are related to recurrence and survival in patients with stage IIIC endometrial carcinoma in this study.Materials and MethodsA total of 147 patients who underwent staging surgery and had a diagnosis of stage IIIC1 to IIIC2 endometrial cancer according to the International Federation of Gynecology and Obstetrics 2009 were included. Patients whose data could not be obtained and patients with a diagnosis of uterine sarcoma and with synchronous tumors were excluded.ResultsMean age of the patients was 58.6 years. Among these patients, 63 had stage IIIC1 and 84 had stage IIIC2 disease. Extrauterine spread was detected in 22% of the patients. Median number of paraaortic (PA) and pelvic lymph nodes removed were 16.5 and 38, respectively. Paraaortic and pelvic nodal involvements were detected in 84 patients and 125 patients, respectively. Radiotherapy was applied more commonly as an adjuvant therapy. Three-year progression-free survival (PFS) and 3-year disease-specific survival (DSS) were 65% and 84%, respectively. Seventy percent of the recurrences were outside the pelvis. Site of metastatic lymph nodes and the number of metastatic PA lymph nodes were associated with 3-year PFS and lymphovascular space invasion; site of metastatic lymph nodes and the presence of recurrence were associated with 3-year DSS in the univariate analysis. Although any surgicopathological factor was not related to 3-year PFS, only the presence of recurrence was an independent prognostic factor for a 3-year DSS in the multivariate analysis (hazard ratio, 0.017; 95% confidence interval, 0.002–0.183).ConclusionsThe number of debulked metastatic lymph nodes and PA involvement were associated with recurrence in the univariate analysis. The presence of recurrence was the only independent prognostic factor detecting survival. Therefore, systematic lymphadenectomy involving PA lymph nodes instead of sampling should be performed in patients with high risk for nodal involvement in endometrial cancer.

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The first evidence for SLFN11 expression as an independent prognostic factor for patients with esophageal cancer after chemoradiotherapy

BMC Cancer ◽

10.1186/s12885-020-07574-x ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Takuma Kagami ◽

Mihoko Yamade ◽

Takahiro Suzuki ◽

Takahiro Uotani ◽

Shinya Tani ◽

...

Keyword(s):

Prognostic Factor ◽

Prognostic Value ◽

Clinical Stage ◽

In Vitro Study ◽

Independent Prognostic Factor ◽

Esophageal Function ◽

Kaplan Meier ◽

Potential Biomarker ◽

Highly Sensitive

Abstract Background Schlafen 11 (SLFN11) was recently identified as a dominant determinant of sensitivity to DNA-targeting agents including platinum-based drugs. SLFN11 also reportedly enhances cellular radiosensitivity. In this study, we examined the prognostic value of SLFN11 expression in esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy (dCRT), including the platinum derivative nedaplatin. Methods Seventy-three patients with ESCC who received dCRT were examined. SLFN11 expression was analyzed in pre-dCRT biopsies using immunohistochemistry and evaluated using a histo-score (H-score). Correlation between the H-score and overall survival was analyzed. An H-score ≥ 51 was provisionally defined as indicating high SLFN11 expression. Viability assays were performed using previously established isogenic human cell lines differentially expressing SLFN11 to test the usefulness of SLFN11 as marker of response to the dCRT regimen. Results High SLFN11 expression was independently associated with better prognosis in ESCC patients (hazard ratio = 0.295, 95% CI = 0.143–0.605, p = 0.001 for multivariate analysis). Kaplan-Meier survival curves showed that the prognostic value of high SLFN11 expression was most evident in patients at clinical stages II and III (p = 0.004). In in vitro study, SLFN11-proficient cells were highly sensitive to platinum derivatives compared to SLFN11-deficient cells. Conclusion SLFN11 expression is an independent prognostic factor for ESCC patients treated with dCRT and a potential biomarker for treatment selection of ESCC. Examination of SLFN11 may be particularly useful for clinical Stage II–III patients who wish to choose dCRT (instead of surgery) to preserve esophageal function.

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