Purpose Gastric cancer (GC) remains a prevalent aggressive tumor with high morbidity and mortality globally. The identification of GC subtypes based on molecular features improved the prediction of prognosis and the selection of targeted therapies. PTEN is a characteristic tumor suppressor, while its association with different GC subtypes was unknown. Patients and Methods The cohort consisted of 248 patients diagnosed with gastric cancer who were hospitalized and received radical gastrectomy. In addition, PTEN gene expression matrix of STAD was retrieved from TCGA. The mRNA and protein levels of PTEN and PD-L1 were detected using qRT-PCR and IHC staining. Multivariate logistic regression and Kaplan–Meier analysis were used to examine the relationship between PTEN expression and clinical characteristics. Results In our study, PTEN was downregulated in gastric tumors both in mRNA and protein levels. Its inactivation was closely linked to higher histological grade ( P = 0.005), neural invasion ( P = 0.012), depth of invasion ( P = 0.021), lymph metastasis ( P = 0.026), and TNM stage ( P = 0.001) of GC in the present study. Moreover, according to the molecular subtypes, high PTEN expression was related to high TPS score of PD-L1 positively ( P = 0.010) but was not associated with MSI and EBV infection. Further, TCGA data validated that PTEN was indeed correlated with histological grade and invasion depth and positively related to PD-L1 expression (R = 0.29, adjusted P < 0.001). Conclusion The above results suggested that PTEN expression was a useful marker in gastric carcinogenesis and progression and in the selection of immunotherapy-based treatments for GC patients.

BACKGROUND Most gastric cancer (GC) patients are diagnosed at middle or late stage because the symptoms in early stage are obscure, which causes higher mortality rates of GC. Helicobacter pylori ( H. pylori ) was identified as a class I carcinogen and leads to aberrant DNA methylation/hydroxymethylation. 5-hydroxymethylcytosine (5-hmC) plays complex roles in gene regulation of tumorigenesis and can be considered as an activating epigenetic mark of hydroxymethylation. AIM To explore the association between 5-hmC levels and the progression and prognosis of GC patients with or without H. pylori infection . METHODS A retrospective cohort study was conducted to estimate the predicted value of 5-hmC level in the progression and prognosis of GC patients with different H. pylori infection status. A total of 144 GC patients were recruited. RESULTS The levels of 5-hmC were significantly decreased in tumor tissues (0.076 ± 0.048) compared with the matched control tissues (0.110 ± 0.057, P = 0.001). A high level of 5-hmC was an independent significant favorable predictor of overall survival in GC patients (hazard ratio = 0.61, 95% confidence interval: 0.38-0.98, P = 0.040), the H. pylori -negative GC subgroup (hazard ratio = 0.30, 95% confidence interval: 0.13-0.68, P = 0.004) and the GC patients with TNM stage Ⅰ or Ⅱ (hazard ratio = 0.32, 95% confidence interval: 0.13-0.77, P = 0.011). CONCLUSION Increased 5-hmC is a favorable prognostic factor in GC, especially for H. pylori -negative subgroups.

PurposeThe aim of this study is to evaluate the efficacy and toxicity of image-guided high-dose rate (HDR) interstitial brachytherapy (ISBT) for the reirradiation of cervical cancer within a previously irradiated area.Methods and materialsTwenty-three consecutive patients with cervical cancer were reirradiated with curative intent using brachytherapy (BT) with or without external beam irradiation. The median biologically equivalent dose in 2-Gy fractions (EQD2) for reirradiation was 64.0 Gy (range: 31.3–95.1 Gy), and the median cumulative EQD2 (for primary treatment and reirradiation) was 152.4 Gy (range: 97.8–200.9 Gy). The average clinical target volume was 82.9 cm3 (range: 26.9–208.3 cm3), and the median treatment-free interval (TFI) was 13 months (range: 3–93 months).ResultsThe median follow-up time was 19 months (range: 2–59 months). The complete response rate after reirradiation was 56.5%. The 1-, 2- 3-, and 4-year post-relapse survival (PRS) rates were 65.2%, 43.5%, 33.8%, and 27.1%, respectively. The median reirradiation EQD2 D2cc of rectum and bladder was 39.5 Gy (range = 14.6–96.2 Gy) and 52.1 Gy (range = 29.1–114.2 Gy). The median cumulative EQD2 D2cc of rectum and bladder was 115.0 Gy (range = 84.4–189.3 Gy) and 130.5 Gy (range = 95.5–173.5 Gy). During follow-up, nine (39.1%) patients had experienced grade 3 or 4 late toxicities. Grade ≥3 rectal toxicity occurred in three patients (13.0%). Grade ≥3 urinary toxicity occurred in five patients (21.7%). One patient (4.3%) had both grade ≥3 urinary and rectal toxicity. Tumor volume, TFI, tumor invasion organ number, and local control were significant prognostic factors adversely affecting OS.ConclusionsFor recurrent cervical cancer after radiotherapy, reirradiation of HDR-ISBT is feasible, even if the local tumor invasion is large, with a good chance of survival and acceptable side effects.