Body mass index and risk of colorectal cancer according to tumor lymphocytic infiltrate
INTERNATIONAL JOURNAL OF CANCER
Authors: Hanyuda, Akiko; Ogino, Shuji; Qian, Zhi Rong; Nishihara, Reiko; Song, Mingyang; Mima, Kosuke; Inamura, Kentaro; Masugi, Yohei; Wu, Kana; Meyerhardt, Jeffrey A.; Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward L.; Cao, Yin
Abstract
Higher body mass index (BMI), higher body adiposity and obesity have been associated with increased risk of colorectal cancer. Evidence suggests that excess energy balance may influence systemic immune and inflammatory status. Thus, we hypothesized that the positive association between BMI and colorectal cancer risk might differ according to colorectal carcinoma subtypes according to levels of histopathological lymphocytic reaction to tumor. We collected biennial questionnaire data on weight and baseline height information in two prospective cohort studies, the Nurses' Health Study (1980-2010) and the Health Professionals Follow-up Study (1986-2010). Utilizing duplication-method Cox proportional hazards regression models, we prospectively assessed the association between BMI and risk of colorectal cancer subtypes according to the degree of Crohn's-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, tumor-infiltrating lymphocytes, the overall lymphocytic reaction score, or T-cell [CD3(+), CD8(+), CD45RO (PTPRC)(+) or FOXP3(+)] density in tumor tissue. Statistical significance level was adjusted for multiple hypotheses testing by Bonferroni correction. During follow up of 1,708,029 men and women (over 3,346,752 person-years), we documented 1,436 incident rectal and colon cancer cases with available formalin-fixed paraffin-embedded tumor tissue materials and pathological immunity data. BMI was significantly associated with higher risk of overall colorectal cancer (P-trend < 0.001); however, the association of BMI with colorectal carcinoma risk did not significantly differ by the level of lymphocytic reaction or T-cell infiltration in tumor tissue status (P-heterogeneity > 0.10). BMI may be associated with risk of colorectal cancer regardless of levels of lymphocytic response to tumor.
Prognostication of a 13-immune-related-gene signature in patients with early triple-negative breast cancer
BREAST CANCER RESEARCH AND TREATMENT
Authors: Kim, Ji-Yeon; Jung, Hae Hyun; Sohn, Insuk; Woo, Sook Young; Cho, Hyun; Cho, Eun Yoon; Lee, Jeong Eon; Kim, Seok Won; Nam, Seok Jin; Park, Yeon Hee; Ahn, Jin Seok; Im, Young-Hyuck
Abstract
Purpose We investigated the expression profiles of immune genes in patients with triple-negative breast cancer (TNBC) to identify the prognostic value of immune genes and their clinical implications. Methods NanoString nCounter Analysis of 770 immune-related genes was used to measure immune gene expression in patients with TNBC who underwent curative surgery followed by adjuvant chemotherapy at Samsung Medical Center between 2000 and 2004. Statistical analyses were conducted to identify the associations between gene expression and distant recurrence-free survival (DRFS). Results Of 1189 patients who underwent curative BC surgery, 200 TNBC patients were included and stage was the only clinical factor predictive of DRFS. In terms of immune genes, 155 of 770 genes were associated with DRFS (p < 0.01). Further multivariate analysis revealed that 13 genes,CD1B,CD53,CT45A1,GTF3C1,IL11RA,IL1RN,LRRN3,MAPK1,NEFL,PRKCE,PTPRC,SPACA3andTNFSF11, were associated with patient prognosis (p < 0.05). The prognostic value of stage and expression levels of 13 immune genes was analyzed and the area under the receiver operating characteristic curve (AUC) was 0.923. Based on the AUC, we divided patients into three genetic risk groups and DRFS rate was significantly different according to genetic risk groups, even in the same stage (p < 0.001). Conclusions In this study, a 13-gene expression profile in combination with stage precisely predicted distant recurrence of early TNBC. Therefore, this 13-immune-gene signature could help predict TNBC prognosis and provide guidance for treatment as well as the opportunity to develop new targets for immunotherapy in TNBC patients.