Expression profiling of esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy: Clinical implications

Abstract

Abstract. In esophageal squamous cell carcinoma (ESCC), chemoradiotherapy (CRT) has a curative potential even in cases of locally advanced carcinoma. However, only about half of the patients benefit from CRT, and an accurate prediction of sensitivity to CRT is eagerly awaited. Using microarrays, we analyzed gene-expression patterns of pretreatment biopsy specimens from 33 patients with CRT alone including longterm survivors, more than 3 years (14 cases) and short-term survivors, less than 1 year (11 cases). The expression patterns of about 12,600 genes were used to identify genes correlated with survival terms. Fifty-seven genes correlating with shortterm survival and 120 genes with long-term survival were identified. The genes involved in the immune response were characteristically upregulated in the long-term survivors, and an immunohistochemical staining confirmed an increased CD8-positive T cell number in the long-term survivors over that in the short-term survivors. In the short-term survivors, on the other hand, increased expression of the genes involved in drug resistance was observed. Our gene list should contribute to the elucidation of the mechanisms of CRT response and contains useful markers for predicting the prognosis of individual ESCC patients treated with CRT alone.

Predominant infiltration of macrophages and CD8+ T Cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer

“…[39][40][41] The effect of chemoradiotherapy in esophageal cancer is correlated with the number of CD8 1 T cells in the tumor of each patient, and the patterns of gene expressions for T cell activation and for tumor vessel formation may become good markers for identifying potential long-term survivors. 11 However, in the present study, no correlations between numbers of macrophages, CD8 1 T cells, or mast cells and response to first-line chemotherapy were found ( Table 2). The results of our study suggested that patients with a favorable or unfavorable prognosis could be identified by the status of tumor-infiltrating macrophages and CD8 1 T cells in tumor biopsy specimens before receiving chemotherapy regardless of chemotherapy response.…”

“…29 The presence of tumor-infiltrating CD8 1 T cells has previously been reported to be associated with a favorable outcome, the same as in our own study. [5][6][7][8][9][10][11][12]30 Patients in the HNM and HNT group had significantly better survival (median survival was 495 days; 1-year survival rate was 68.5%) than patients in the HNM group (median survival, 440 days; 1-year survival rate, 60.8%; Fig. 2C) and patients in the HNT group (median survival, 388 days; 1-year survival rate, 53.4%; Fig.…”

“…17,18 Tumor-infiltrating immune cells are thought to play important roles in disease progression and therapeutic efficacy. The effect of chemoradiotherapy has been found to be correlated with the presence of CD8 1 T cells in esophageal cancer, 11 and cervical cancer patients with T-cell infiltration showed improved local response to radiation therapy. 19 In the current study, we evaluated the status of tumor-infiltrating immune cells in tumor biopsy specimens obtained from stage IV NSCLC patient and analyzed the numbers of immune cells and clinical outcome, including chemotherapy response and prognosis, for correlations.…”

“…Infiltration of CD8 1 T cells has been shown to be an important phenomenon for a specific immune response in several tumor systems, and CD8 1 T cells have been reported to play an important suppressive role in cancer progression, including ovarian cancer, esophageal cancer, pancreatic cancer, bile duct cancer, gallbladder cancer, and colorectal cancer. [5][6][7][8][9][10][11][12] Immunologists have long considered the presence of tumor-infiltrating macrophages as evidence of a host response against the growing tumor, and the presence of tumor-infiltrating macrophages has been reported to be associated with anticancer immunomechanisms of the tumorbearing host and a favorable prognosis. However, recently, tumor-associated macrophage infiltration has been found to be correlated with angiogenesis and an unfavorable prognosis in several kinds of cancer, including gastric cancer, endometrial cancer, and breast cancer.…”

Overexpression of astrocyte elevated gene-1 (AEG-1) is associated with esophageal squamous cell carcinoma (ESCC) progression and pathogenesis

“…Despite rapid advancement of multimodal treatments for patients afflicted with ESCC, the prognosis has not been significantly improved, with an average 5 years survival rate of 10-20% (2,5,6). The prediction of ESCC clinical prognosis still depends on conventional pathologic variables such as tumor size, tumor grade, lymph node and distal metastasis status (7)(8)(9). Therefore, it is of great clinical value to find sensitive and specific early biomarkers for the diagnosis and prognosis of this malignancy, as well as novel therapeutic strategies.…”